Lisinopril Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Dizziness, lightheadedness, tiredness, or headache may occur as your body adjusts to the medication. Dry cough may also occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: fainting, symptoms of a high potassium blood level (such as muscle weakness, slow/irregular heartbeat).

Although lisinopril may be used to prevent kidney problems or treat people who have kidney problems, it may also rarely cause serious kidney problems or make them worse. Your doctor will check your kidney function while you are taking lisinopril. Tell your doctor right away if you have any signs of kidney problems such as a change in the amount of urine.

Lisinopril may rarely cause serious (possibly fatal) liver problems. Get medical help right away if you have any symptoms of liver damage, such as: nausea/vomiting that doesn’t stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US –

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www. fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Lisinopril: medicine to treat high blood pressure

It’s usual to take lisinopril once a day.

Your doctor may suggest that you take your first dose before bedtime because it can make you dizzy.

After the very first dose, you can take lisinopril at any time of day. Try to take it at the same time every day.

Dosage

The dose of lisinopril you take depends on why you need the medicine. Take it as instructed by your doctor.

To decide your dose, your doctor will check your blood pressure and ask you if you’re getting any side effects.

You may also have blood tests to check how well your kidneys are working and the amount of potassium in your blood.

Depending on why you’re taking lisinopril, the usual starting dose is between 2.5mg and 10mg once a day.

This will be increased gradually over a few weeks to a usual dose of:

• 20mg once a day for high blood pressure (the maximum dose is 80mg once a day)
• 10mg once a day after a recent heart attack
• 20mg to 35mg once a day for heart failure
• 10mg to 20mg once a day for diabetic kidney disease

Doses are usually lower for children.

How to take it

You can take lisinopril with or without food. Swallow lisinopril tablets whole with a drink.

If you’re taking lisinopril as a liquid, it’ll come with a plastic syringe or spoon to help you measure out the right dose.

If you do not have one, ask your pharmacist for one. Do not use a kitchen teaspoon as it will not give the right amount of medicine.

Will my dose go up or down?

You’ll probably be prescribed a low dose of lisinopril at first so it does not make you feel dizzy.

This will usually be increased gradually until you reach the right dose for you.

If you have side effects with lisinopril, you may stay on a lower dose.

What if I get ill while I’m taking it?

If you get severe diarrhoea or vomiting for any reason, stop taking lisinopril.

When you’re able to eat and drink normally, wait for 24 to 48 hours, then start to take it again.

If you have questions about this, contact your doctor or pharmacist.

What if I forget to take it?

If you miss a dose of lisinopril, take it as soon as you remember.

If you do not remember until the following day, skip the missed dose. Do not take a double dose to make up for a forgotten one.

If you forget doses often, it may help to set an alarm to remind you.

You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

What if I take too much?

If you take too many lisinopril tablets by accident, contact your doctor or go to your nearest A&E.

Taking too much lisinopril can cause dizziness, sleepiness and a pounding heartbeat.

The amount of lisinopril that can lead to an overdose varies from person to person.

Side effects, dosage, uses, and more

1. Lisinopril is an oral drug that’s used to treat hypertension (high blood pressure) and heart failure. It’s also used to improve your chance of survival after a heart attack. This drug may be taken alone or with other medications to treat your condition.
2. The standard starting dose for adults with high blood pressure is 10 mg taken by mouth once per day. Your doctor may increase your dose up to a maximum of 80 mg per day. The starting dose for adults with heart failure is 5 mg per day. Your doctor may increase your dose up to a maximum of 40 mg per day.
3. This drug may cause abrupt swelling of your face, arms, legs, lips, tongue, throat, and intestines (angioedema). This can be fatal.
4. You shouldn’t take lisinopril if you’re pregnant or plan to become pregnant. This drug can harm or be fatal to your unborn baby.
5. Common side effects include headache, dizziness, persistent cough, low blood pressure, and chest pain.

• Angioedema (swelling): This drug can cause abrupt swelling of your face, arms, legs, lips, tongue, throat, and intestines. This can be fatal. Tell your doctor right away if you have swelling or abdominal pain. You’ll be taken off of this drug and possibly given medication to reduce your swelling. Swelling can happen at any time while you’re taking this drug. Your risk may be higher if you have a history of angioedema.
• Hypotension (low blood pressure): This drug can cause low blood pressure, especially during the first few days of taking it. Tell your doctor if you feel lightheaded, dizzy, or like you’re going to faint. You may be more likely to have low blood pressure if you:
• aren’t drinking enough fluids
• are sweating heavily
• have diarrhea or are vomiting
• have heart failure
• are on dialysis
• take diuretics
• Persistent cough: This drug may cause a persistent cough. This cough will go away once you stop taking the medication.

Lisinopril oral tablet is a prescription drug that’s available as the brand-name drugs Prinivil and Zestril. It’s also available as a generic drug. Generic drugs usually cost less. In some cases, they may not be available in every strength or form as the brand-name version.

Why it’s used

This drug is used to treat high blood pressure and heart failure. It’s also used to improve your chance of survival after a heart attack.

This drug may be used as part of a combination therapy. That means you may need to take it with other drugs.

How it works

This drug belongs to a class of drugs called angiotensin-converting enzyme (ACE) inhibitors.

A class of drugs is a group of medications that work in a similar way. They have a similar chemical structure and are often used to treat similar conditions.

This drug relaxes the blood vessels in your body. This reduces stress on your heart and lowers your blood pressure.

Lisinopril oral tablet does not cause drowsiness. However, it may cause low blood pressure. This can make you feel faint or dizzy. You shouldn’t drive, use machinery, or do other activities that require alertness until you know how this drug affects you. Lisinopril can also have other side effects.

More common side effects

The most common side effects that occur with lisinopril include:

• headache
• dizziness
• persistent cough
• low blood pressure
• chest pain

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have any of these serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

• hypersensitivity (allergic) reaction. Symptoms include:
• swelling of your face, lips, tongue, or throat
• trouble breathing
• trouble swallowing
• stomach (abdomen) pain with or without nausea or vomiting
• kidney problems. Symptoms include:
• tiredness
• swelling, especially of your hands, feet, or ankles
• shortness of breath
• weight gain
• liver failure. Symptoms include:
• yellowing of your skin and the whites of your eyes
• elevated liver enzymes
• stomach pain
• nausea and vomiting
• high potassium levels. This drug can cause dangerously high potassium. This can lead to arrhythmia (heart rate or rhythm problems). Your risk may be higher if you have kidney disease or diabetes, or if you’re taking other drugs that increase potassium levels.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.

Lisinopril oral tablet can interact with other medications, herbs, or vitamins you might be taking. An interaction is when a substance changes the way a drug works. This can be harmful or cause the drugs that you take to not work as well.

To help prevent interactions, your doctor should manage all of your medications carefully. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with lisinopril are listed below.

Blood pressure drugs

Taking certain blood pressure drugs with lisinopril increases your risk for low blood pressure, high blood potassium, and kidney problems including kidney failure. These drugs include:

• angiotensin receptor blockers (ARB). Examples include:
• candesartan (Atacand, Atacand HCT)
• eprosartan (Teveten)
• irbesartan (Avapro, Avalide)
• losartan (Cozaar, Hyzaar)
• olmesartan (Benicar, Benicar HCT, Tribenzor, Azor)
• telmisartan (Micardis, Micardis HCT, Twynsta)
• valsartan (Diovan, Diovan HCT, Exforge, Exforge HCT)
• azilsartan (Edarbi, Edarbyclor)
• angiotensin-converting enzyme (ACE) inhibitors. Examples include:
• benazepril (Lotensin, Lotrel, Lotensin HCT)
• captopril
• enalapril (Vasotec, Epaned)
• fosinopril (Monopril)
• lisinopril (Prinivil, Zestril, Prinzide, Zestoretic)
• moexipril (Uniretic)
• perindopril (Aceon)
• quinapril (Accupril, Accuretic)
• ramipril (Altace)
• trandolapril (Mavik, Tarka)
• renin inhibitors:
• aliskiren (Tekturna, Tekturna HCT)

Diabetes drugs

Taking diabetes drugs with lisinopril can lower your blood sugar level too much. These drugs include:

• insulins
• oral diabetes drugs

Water pills (diuretics)

Taking water pills with lisinopril can make your blood pressure too low. These drugs include:

• hydrochlorothiazide
• chlorthalidone
• furosemide
• bumetanide

Potassium supplements and potassium-sparing diuretics

Taking potassium supplements or potassium-sparing diuretics with lisinopril can increase potassium in your body. These drugs include:

• spironolactone
• amiloride
• triamterene

Mood stabilizer drugs

Lisinopril can increase the effects of lithium. This means that you may have more side effects.

Pain drugs

Taking certain pain drugs with lisinopril can decrease your kidney function. These drugs include:

Neprilysin inhibitors

These drugs are used to treat heart failure. They should not be used with enalapril. Do not use enalapril within 36 hours of switching to or from a neprilysin inhibitor. Using these drugs together raises your risk of sudden swelling of your face, arms, legs, lips, tongue, throat, and intestines (angioedema).

An example of this drug class includes:

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

Allergy warning

This drug can cause a severe allergic reaction. Symptoms include:

• trouble breathing
• swelling of your throat or tongue
• hives

Call 911 or go to the nearest emergency room if you develop these symptoms.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Alcohol interaction

The use of drinks that contain alcohol can increase the blood pressure-lowering effects of lisinopril. This may cause you to feel dizzy or faint. If you drink alcohol, talk to your doctor.

Warnings for people with certain health conditions

For people with kidney disease: If you have kidney disease or are on dialysis, you have a higher risk of getting certain serious side effects from this drug. Your doctor will monitor your kidney function and adjust your medication as needed. Your doctor should start you on a lower dose of this drug.

For people with diabetes: This drug can affect your blood sugar levels. Your doctor may need to change your dose of your diabetes medicines. Your doctor will tell you how often to test your blood sugar levels.

Warnings for other groups

For pregnant women: This drug is a category D pregnancy drug. That means two things:

1. Research in humans has shown adverse effects to the fetus when the mother takes the drug.
2. This drug should only be used during pregnancy in serious cases where it’s needed to treat a dangerous condition in the mother.

Talk to your doctor if you’re pregnant or planning to become pregnant. Ask your doctor to tell you about the specific harm that may be done to the fetus. This drug should be only used if the potential risk to the fetus is acceptable given the drug’s potential benefit.

For women who are breastfeeding: It isn’t known if this drug passes into breast milk. If it does, it may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your baby. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors: Older adults may process drugs more slowly. A normal adult dose may cause levels of this drug to be higher than normal in your body. If you’re a senior, you may need a lower dose or a different schedule.

For children: This medicine hasn’t been studied and shouldn’t be used in children younger than 6 years.

This dosage information is for lisinopril oral tablet. All possible dosages and forms may not be included here. Your doctor will tell you what dosage is right for you. Your dose, form, and how often you take it will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how you react to the first dose

Forms and strengths

Generic: lisinopril

• Form: Oral tablet
• Strengths: 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg

Brand: Prinivil

• Form: Oral tablet
• Strengths: 5 mg, 10 mg, 20 mg

Brand: Zestril

• Form: Oral tablet
• Strengths: 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg

Dosage for hypertension

Adult dosage (ages 18–64 years)

• Starting dose: 10 mg taken by mouth once per day
• Usual dose: 20–40 mg taken once per day
• Maximum dose: 80 mg taken once per day

Child dosage (ages 6–17 years)

• Starting dose: 0.07 mg/kg of body weight taken by mouth once per day
• Dose adjustments will be based on your blood pressure response.
• Maximum dose: 0.61 mg/kg, up to 40 mg, once per day

Child dosage (ages 0–5 years)

This medicine hasn’t been studied and shouldn’t be used in children younger than 6 years.

Senior dosage (ages 65 years and older)

There are no specific recommendations for senior dosing. Older adults may process drugs more slowly. A normal adult dose may cause levels of this drug to be higher than normal in your body. If you’re a senior, you may need a lower dose or a different schedule.

Dosage for heart failure

Adult dosage (ages 18–64 years)

• Starting dose: 5 mg taken by mouth once per day
• Maximum dose: 40 mg taken once per day

Child dosage (ages 0–17 years)

This medicine hasn’t been studied and shouldn’t be used in children younger than 18 years for heart failure.

Senior dosage (ages 65 years and older)

There are no specific recommendations for senior dosing. Older adults may process drugs more slowly. A normal adult dose may cause levels of this drug to be higher than normal in your body. If you’re a senior, you may need a lower dose or a different schedule.

Dosage for acute myocardial infarction (heart attack)

Adult dosage (ages 18–64 years)

• Starting dose: 5 mg taken by mouth within the first 24 hours of when symptoms of heart attack start. Your doctor will give you another 5 mg after another 24 hours.
• Usual dose: 10 mg given 48 hours after heart attack. Then 10 mg taken once per day for at least 6 weeks.

Child dosage (ages 6–17 years)

This medicine hasn’t been studied and shouldn’t be used in children younger than 18 years for improving survival after a heart attack.

Child dosage (ages 0–5 years)

This medicine hasn’t been studied and shouldn’t be used in children younger than 6 years.

Senior dosage (ages 65 years and older)

There are no specific recommendations for senior dosing. Older adults may process drugs more slowly. A normal adult dose may cause levels of this drug to be higher than normal in your body. If you’re a senior, you may need a lower dose or a different schedule.

Special considerations

• Heart failure: If you have low blood sodium levels, your starting dose may be 2.5 mg taken once per day.
• Improving survival after a heart attack: If you have low blood pressure, your starting dose may be 2.5 mg for the first 3 days after having a heart attack.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always to speak with your doctor or pharmacist about dosages that are right for you.

Lisinopril oral tablet is used for long-term treatment. This drug comes with serious risks if you don’t take it as prescribed.

If you don’t take it at all: If you don’t take it at all, your blood pressure will stay high. This will raise your risk for a heart attack and stroke.

If you stop taking it suddenly: If you stop taking this drug suddenly, your blood pressure may spike. This can cause anxiety, sweating, and a fast heart rate.

If you don’t take it on schedule: You may not feel any different, but your blood pressure may not be controlled. This can put you at higher risk for heart attack and stroke.

What to do if you miss a dose: If you forget to take your dose, take it as soon as you remember. If it’s just a few hours until the time for your next dose, then wait and only take one dose at that time. Never try to catch up by taking two doses at once. This could result in toxic side effects.

If you take too much: If you take too much of this drug, you may have a drop in blood pressure. This may cause you to faint. If you think you’ve taken too much of the drug, act right away. Call your doctor or local Poison Control Center, or go to the nearest emergency room.

How to tell this drug is working: Your doctor will monitor your blood pressure and other symptoms of your condition to tell if this drug is working for you. You also may be able to tell this drug is working if you check your blood pressure and it’s lower.

Keep these considerations in mind if your doctor prescribes lisinopril oral tablet for you.

General

This drug should be taken around the same time every day.You can crush or cut the tablet.

Storage

• Keep it from 59°F (20°C) to 86°F (25°C).
• Keep your drugs away from areas where they could get wet, such as bathrooms. Store this drug away from moisture and damp locations.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry it with you or in your carry-on bag.
• Don’t worry about airport x-ray machines. They can’t hurt your medication.
• You may need to show airport security staff the pharmacy prescription label for your medication. Always carry the original prescription-labeled box with you.
• Don’t leave this medicine in the car, especially when the temperature is hot or freezing.

Self-management

Your doctor may ask you to check your blood pressure at home. To do this, you’ll need to purchase a home blood pressure monitor. These are available at most pharmacies. You should keep a log with the date, time of day, and your blood pressure readings. Bring this diary with you to your doctor appointments.

Clinical monitoring

Before starting and during your treatment with this drug, your doctor may check the following to tell if this drug is working or is safe for you:

• blood pressure
• liver function
• kidney function
• blood potassium

Hidden costs

You may need to buy a blood pressure monitor to check your blood pressure at home.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other options that may work for you.

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

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Lisinopril – Overview

Lisinopril is a medication used to treat high blood pressure and heart failure that is available as generic lisinopril or branded lisinopril marketed under brand names like Prinivil and Zestril. People interested in getting a prescription for lisinopril pills can connect with licensed medical providers through Push Health and, when appropriate, get their lisinopril prescription medication delivered or made available for pickup at a local pharmacy.

Lisinopril Pill – How It Works

Lisinopril is an oral medication that belongs to a class of medications known as an angiotensin-converting enzyme (ACE) inhibitors – similar to benazepril, captopril, enalapril and quinapril. ACE inhibitors like lisinopril are thought to lower blood pressure by suppressing the renin-angiotensin-aldosterone system. In adults, lisinopril administration reduces standing and supine blood pressure with minimal increase in the heart rate. The effect on blood pressure is additive when lisinopril is utilized at the same time as a thiazide-type diuretic such as in a lisinopril – hydrochlorothiazide (HCTZ) combinations known as Prinzide and Zestoretic.

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Lisinopril – Dosage and Cost

The lisinopril used to formulate tablets is a white to off-white crystalline powder that is soluble in water. Lisinopril pills are typically round, biconvex uncoated tablets that can be white, pink, red or yellow, depending on the lisinopril dosage in the tablet. Lisinopril tablets are supplied in 2.5mg, 5mg, 10mg, 20mg, 30mg and 40mg tablets. Inactive ingredients that can be found in lisinopril tablets include calcium phosphate, magnesium stearate, mannitol and starch. Lisinopril tablets should be stored at room temperature and protected from moisture, freezing and excessive heat. Lisinopril tablets are moderately affordable, costing under $1 per lisinopril tablet. Lisinopril coupons might be available from a variety of sources and some insurance plans may also help with costs associated with a lisinopril prescription.

Lisinopril – Absorption and Half-Life

Lisinopril reaches peak serum concentrations about seven hours after oral administration. When taken orally, the absorption of lisinopril is not generally affected if the medication is taken with food. The effective half-life of lisinopril after oral administration is twelve hours. Many people will see effects on their blood pressure from one to twenty-four hours after a dose of lisinopril. Other people will need up to four weeks before the target blood pressure is reached. Lisinopril does not seem to bind to other proteins in the serum and is excreted in the urine. Because it is processed by the kidneys, impaired renal function can decrease the amount of lisinopril eliminated from the body.

Can I Buy Lisinopril Online?

Generic lisinopril requires a valid prescription in the United States before lisinopril tablets can be dispensed by a pharmacy. For this reason, lisinopril OTC is not available and one cannot just buy lisinopril online without first consulting a licensed provider. Push Health is set up to connect people who need a prescription for lisinopril with a licensed medical provider who can prescribe lisinopril tablets, including generic lisinopril 2.5 mg tablets, lisinopril 5 mg tablets, lisinopril 10 mg tablets, lisinopril 20 mg tablets and lisinopril 40 mg tablets, when appropriate.

Lisinopril – Side Effects

Lisinopril can cause side effects but is typically tolerated well. Side effects of lisinopril include nausea, headache, dizziness, and a rash. More serious side effects include liver problems, high potassium levels, low blood pressure, and angioedema. Like all medications, lisinopril can cause allergic reactions in susceptible people. All concerns about side effects are best directed to the pharmacist and one’s prescribing medical provider.

More Lisinopril Information

Last updated February 6, 2021. Given the evolving nature of medicine and science, this information might not be accurate and should not be construed as medical advice or diagnosis / treatment recommendations. Please consult a licensed medical provider if you have additional questions.

Lisinopril 20mg Tablets – Summary of Product Characteristics (SmPC)

This information is intended for use by health professionals

Each tablet contains lisinopril dihydrate equivalent to 20 mg anhydrous lisinopril.

For the full list of excipients, see section 6.1

Tablets.

20 mg tablets are white, round biconvex tablets with embossing “20” on one side and breakline on the other side.

The tablets can be divided into equal halves.

Hypertension

Treatment of hypertension.

Heart Failure

Treatment of symptomatic heart failure.

Acute Myocardial Infarction

Short-term (6 weeks) treatment of haemodynamically stable patients within 24 hours of an acute myocardial infarction.

Renal Complications of Diabetes Mellitus

Treatment of renal disease in hypertensive patients with Type 2 diabetes mellitus and incipient nephropathy (see section 5.1).

Lisinopril can be used alone or in combination with other antihypertensive agents (see sections 4.3, 4.4, 4.5 and 5.1).

Lisinopril tablets should be administered orally in a single daily dose. As with all other medication taken once daily, Lisinopril tablets should be taken at approximately the same time each day. The absorption of Lisinopril tablets is not affected by food.

The dose should be individualised according to patient profile and blood pressure response (see section 4.4)

Hypertension

Lisinopril tablets may be used as monotherapy or in combination with other classes of antihypertensive therapy (see sections 4.3, 4.4, 4.5 and 5.1).

Starting dose

In patients with hypertension the usual recommended starting dose is 10 mg. Patients with a strongly activated renin-angiotensin-aldosterone system (in particular, renovascular hypertension, salt and /or volume depletion, cardiac decompensation, or severe hypertension) may experience an excessive blood pressure fall following the initial dose. A starting dose of 2.5-5 mg is recommended in such patients and the initiation of treatment should take place under medical supervision. A lower starting dose is required in the presence of renal impairment (see Table 1 below).

Maintenance dose

The usual effective maintenance dosage is 20 mg administered in a single daily dose. In general if the desired therapeutic effect cannot be achieved in a period of 2 to 4 weeks on a certain dose level, the dose can be further increased. The maximum dose used in long-term, controlled clinical trials was 80 mg/day.

Diuretic-Treated Patients

Symptomatic hypotension may occur following initiation of therapy with Lisinopril tablets. This is more likely in patients who are being treated currently with diuretics. Caution is recommended therefore, since these patients may be volume and/or salt depleted. If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with Lisinopril tablets. In hypertensive patients in whom the diuretic cannot be discontinued, therapy with Lisinopril tablets should be initiated with a 5 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of Lisinopril tablets should be adjusted according to blood pressure response. If required, diuretic therapy may be resumed (see section 4.4 and section 4.5).

Dosage Adjustment In Renal Impairment

Dosage in patients with renal impairment should be based on creatinine clearance as outlined in Table 1 below.

Table 1 Dosage adjustment in renal impairment.

* Dosage and/or frequency of administration should be adjusted depending on the blood pressure response.

The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.

Use in Hypertensive Paediatric Patients aged 6-16 years

The recommended initial dose is 2. 5 mg once daily in patients 20 to <50 kg, and 5 mg once daily in patients ≥50 kg. The dosage should be individually adjusted to a maximum of 20 mg daily in patients weighing 20 to <50 kg, and 40 mg in patients ≥50 kg. Doses above 0.61 mg/kg (or in excess of 40 mg) have not been studied in paediatric patients (see section 5.1).

In children with decreased renal function, a lower starting dose or increased dosing interval should be considered.

Heart Failure

In patients with symptomatic heart failure, Lisinopril tablets should be used as adjunctive therapy to diuretics and, where appropriate, digitalis or beta-blockers. Lisinopril tablets may be initiated at a starting dose of 2.5 mg once a day, which should be administered under medical supervision to determine the initial effect on the blood pressure. The dose of Lisinopril tablets should be increased:

• By increments of no greater than 10 mg

• At intervals of no less than 2 weeks

• To the highest dose tolerated by the patient up to a maximum of 35 mg once daily.

Dose adjustment should be based on the clinical response of individual patients.

Patients at high risk of symptomatic hypotension e.g. patients with salt depletion with or without hyponatraemia, patients with hypovolaemia or patients who have been receiving vigorous diuretic therapy should have these conditions corrected, if possible, prior to therapy with Lisinopril tablets. Renal function and serum potassium should be monitored (see section 4.4).

Posology in Acute Myocardial Infarction

Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin, and beta-blockers. Intravenous or transdermal glyceryl trinitrate may be used together with Lisinopril tablets.

Starting dose (first 3 days after infarction)

Treatment with Lisinopril tablets may be started within 24 hours of the onset of symptoms. Treatment should not be started if systolic blood pressure is lower than 100 mm Hg. The first dose of Lisinopril tablets is 5 mg given orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Patients with a low systolic blood pressure (120 mm Hg or less) when treatment is started or during the first 3 days after the infarction should be given a lower dose – 2.5 mg orally (see section 4.4).

In cases of renal impairment (creatinine clearance <80 ml/min), the initial Lisinopril tablets dosage should be adjusted according to the patient’s creatinine clearance (see Table 1).

Maintenance dose

The maintenance dose is 10 mg once daily. If hypotension occurs (systolic blood pressure less than or equal to 100 mm Hg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure less than 90 mm Hg for more than 1 hour) Lisinopril tablets should be withdrawn.

Treatment should continue for 6 weeks and then the patient should be re-evaluated. Patients who develop symptoms of heart failure should continue with Lisinopril tablets (see section 4.2).

Renal Complications of Diabetes Mellitus

In hypertensive patients with type 2 diabetes mellitus and incipient nephropathy, the dose is 10 mg Lisinopril tablets once daily which can be increased to 20 mg once daily, if necessary, to achieve a sitting diastolic blood pressure below 90 mm Hg.

In cases of renal impairment (creatinine clearance <80 ml/min), the initial Lisinopril tablets dosage should be adjusted according to the patient’s creatinine clearance (see Table 1).

Paediatric population

There is limited efficacy and safety experience in hypertensive children >6 years old, but no experience in other indications (see section 5.1). Lisinopril is not recommended in children in other indications than hypertension.

Lisinopril is not recommended in children below the age of 6, or in children with severe renal impairment (GFR <30ml/min/1.73m²) (see section 5.2).

Elderly

In clinical studies, there was no age-related change in the efficacy or safety profile of the drug. When advanced age is associated with decrease in renal function, however, the guidelines set out in Table 1 should be used to determine the starting dose of Lisinopril tablets. Thereafter, the dosage should be adjusted according to the blood pressure response.

Use in kidney transplant patients

There is no experience regarding the administration of Lisinopril tablets in patients with recent kidney transplantation. Treatment with Lisinopril tablets is therefore not recommended.

• Hypersensitivity to Lisinopril tablets, to any of the excipients listed in section 6.1 or any other angiotensin converting enzyme (ACE) inhibitor

• History of angioedema associated with previous ACE inhibitor therapy

• Concomitant use of Lisinopril tablets with sacubitril/valsartan therapy. Lisinopril tablets must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.4 and 4.5).

• Hereditary or idiopathic angioedema

• Second and third trimesters of pregnancy (see sections 4.4 and 4.6).

• In combination with aliskiren-containing medicines in patients with diabetes mellitus (type I or II) or with moderate to severe renal impairment (GFR < 60 ml/min/1.73m² (see sections 4.5 and 5.1).

Symptomatic Hypotension

Symptomatic hypotension is seen rarely in uncomplicated hypertensive patients. In hypertensive patients receiving Lisinopril tablets, hypotension is more likely to occur if the patient has been volume-depleted e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting, or has severe renin-dependent hypertension (see section 4. 5 and section 4.8). In patients with heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be closely monitored. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.

In some patients with heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with Lisinopril tablets. This effect is anticipated and is not usually a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose or discontinuation of Lisinopril tablets may be necessary.

Hypotension In Acute Myocardial Infarction

Treatment with Lisinopril tablets must not be initiated in acute myocardial infarction patients who are at risk of further serious haemodynamic deterioration after treatment with a vasodilator. These are patients with systolic blood pressure of 100 mm Hg or lower or those in cardiogenic shock. During the first 3 days following the infarction, the dose should be reduced if the systolic blood pressure is 120 mm Hg or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg if systolic blood pressure is 100 mm Hg or lower. If hypotension persists (systolic blood pressure less than 90 mm Hg for more than 1 hour) then Lisinopril tablets should be withdrawn.

Aortic and mitral valve stenosis / hypertrophic cardiomyopathy

As with other ACE inhibitors, Lisinopril tablets should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy.

Renal Function Impairment

In cases of renal impairment (creatinine clearance <80 ml/min), the initial Lisinopril tablets dosage should be adjusted according to the patient’s creatinine clearance (see Table 1 in section 4.2) and then as a function of the patient’s response to treatment. Routine monitoring of potassium and creatinine is part of normal medical practice for these patients.

In patients with heart failure, hypotension following the initiation of therapy with ACE inhibitors may lead to some further impairment in renal function. Acute renal failure, usually reversible, has been reported in this situation.

In some patients with bilateral renal artery stenosis or with a stenosis of the artery to a solitary kidney, who have been treated with angiotensin converting enzyme inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen. This is especially likely in patients with renal insufficiency. If renovascular hypertension is also present there is an increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started under close medical supervision with low doses and careful dose titration. Since treatment with diuretics may be a contributory factor to the above, they should be discontinued and renal function should be monitored during the first weeks of Lisinopril tablets therapy.

Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when Lisinopril tablets has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or Lisinopril tablets may be required.

In acute myocardial infarction, treatment with Lisinopril tablets should not be initiated in patients with evidence of renal dysfunction, defined as serum creatinine concentration exceeding 177 micromol/l and/or proteinuria exceeding 500 mg/24 h. If renal dysfunction develops during treatment with Lisinopril tablets (serum creatinine concentration exceeding 265 micromol/l or a doubling from the pre-treatment value) then the physician should consider withdrawal of Lisinopril tablets.

Hypersensitivity/Angioedema

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely in patients treated with angiotensin converting enzyme inhibitors, including Lisinopril tablets. This may occur at any time during therapy. In such cases, Lisinopril tablets should be discontinued promptly and appropriate treatment and monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patients. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient.

Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema. Patients with involvement of the tongue, glottis or larynx, are likely to experience airway obstruction, especially those with a history of airway surgery. In such cases emergency therapy should be administered promptly. This may include the administration of adrenaline and/or the maintenance of a patient’s airway. The patient should be under close medical supervision until complete and sustained resolution of symptoms has occurred.

Angiotensin converting enzyme inhibitors cause a higher rate of angioedema in black patients than in non-black patients.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see 4.3 ).

Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to the increased risk of angioedema. Treatment with sacubitril/valsartan must not be initiated earlier than 36 hours after the last dose of Lisinopril. Treatment with Lisinopril must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5).

Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin may lead to an increased risk of angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment) (see section 4.5). Caution should be used when starting racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin in a patient already taking an ACE inhibitor.

Anaphylactoid reactions in Haemodialysis Patients

Anaphylactoid reactions have been reported in patients dialysed with high flux membranes (e.g. AN 69) and treated concomitantly with an ACE inhibitor. In these patients consideration should be given to using a different type of dialysis membrane or different class of antihypertensive agent.

Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis

Rarely, patients receiving ACE inhibitors during low-density lipoproteins (LDL) apheresis with dextran sulphate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.

Desensitisation

Patients receiving ACE inhibitors during desensitisation treatment (e.g. hymenoptera venom) have sustained anaphylactoid reactions. In the same patients, these reactions have been avoided when ACE inhibitors were temporarily withheld but they have reappeared upon inadvertent re-administration of the medicinal product.

Hepatic failure

Very rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving Lisinopril tablets who develop jaundice or marked elevations of hepatic enzymes should discontinue Lisinopril tablets and receive appropriate medical follow-up.

Neutropenia/ Agranulocytosis

Neutropenia/ Agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia occurs rarely. Neutropenia and agranulocytosis are reversible after discontinuation of the ACE inhibitor. Lisinopril tablets should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function. Some of these patients developed serious infections, which in a few instances did not respond to intensive antibiotic therapy. If Lisinopril tablets are used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.”

Race

ACE inhibitors cause a higher rate of angioedema in black patients than in non-black patients.

As with other ACE inhibitors, Lisinopril tablets may be less effective in lowering blood pressure in black patients than in non-blacks, possibly because of a higher prevalence of low-renin states in the black hypertensive population.

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

Surgery/Anaesthesia

In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, Lisinopril tablets may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Hyperkalaemia

Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including Lisinopril tablets. Patients at risk for the development of hyperkalaemia include those with renal insufficiency, diabetes mellitus, or those using concomitant potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or those patients taking other drugs associated with increases in serum potassium (e.g. heparin, the combination trimethoprim/sulfamethoxazole also known as cotrimoxazole). If concomitant use of the above-mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended (see section 4.5).

Diabetic patients

In diabetic patients treated with oral antidiabetic agents or insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor (see section 4.5 Interaction with other medicinal products and other forms of interaction).

Lithium

The combination of lithium and Lisinopril tablets is generally not recommended (see section 4.5).

Pregnancy

ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

Antihypertensive agents

When Lisinopril tablets is combined with other antihypertensive agents (e.g. glyceryl trinitrate and other nitrates, or other vasodilators), additive falls in blood pressure may occur.

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1).

Drugs that may increase the risk of angioedema

Concomitant treatment of ACE inhibitors with mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus, sirolimus, everolimus) or neutral endopeptidase (NEP) inhibitors (e.g. racecadotril) or tissue plasminogen activator may increase the risk of angioedema.

Diuretics

When a diuretic is added to the therapy of a patient receiving Lisinopril tablets the antihypertensive effect is usually additive.

Patients already on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure when Lisinopril tablets is added. The possibility of symptomatic hypotension with Lisinopril tablets can be minimised by discontinuing the diuretic prior to initiation of treatment with Lisinopril tablets (see section 4.2 and section 4.4).

Potassium supplements, potassium-sparing diuretics or potassium-containing salt substitutesand other drugs that may increase serum potassium levels

Although in clinical trials, serum potassium usually remained within normal limits, hyperkalaemia did occur in some patients. The use of potassium supplements, potassium-sparing diuretics or potassium-containing salt substitutes and other drugs that may increase serum potassium levels, particularly in patients with impaired renal function, may lead to a significant increase in serum potassium.

Monitoring of potassium should be undertaken as appropriate. See section 4.4. If Lisinopril is given with a potassiumlosing diuretic, diuretic induced hypokalaemia may be ameliorated.

Ciclosporin

Hyperkalaemia may occur during concomitant use of ACE inhibitors with cislosporin.

Monitoring of serum potassium ids recommended.

Heparin

Hyperkalaemia may occur during concomitant use of ACE inhibitors with heparin.

Monitoring of serum potassium is recommended.

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Concomitant use of thiazide diuretics may increase the risk of lithium toxicity and enhance the already increased lithium toxicity with ACE inhibitors. Use of Lisinopril tablets with lithium is not recommended, but if the combination proves necessary, careful monitoring of serum lithium levels should be performed (see section 4.4).

Non steroidal anti-inflammatory drugs (NSAIDs) including acetylsalicylic acid ≥3g/day

When ACE-inhibitors are administered simultaneously with non-steroidal anti-inflammatory drugs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs), attenuation of the antihypertensive effect may occur. Concomitant use of ACE-inhibitors and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. These effects are usually reversible. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.

Gold

Nitritoid reactions (symptoms of vasodilatation including flushing, nausea, dizziness and hypotension, which can be very severe) following injectable gold (for example, sodium aurothiomalate) have been reported more frequently in patients receiving ACE inhibitor therapy.

Tricyclic antidepressants / Antipsychotics /Anaesthetics

Concomitant use of certain anaesthetic medicinal products, tricyclic antidepressants and antipsychotics with ACE inhibitors may result in further reduction of blood pressure (see section 4.4).

Sympathomimetics

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.

Antidiabetics

Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicinal products (insulins, oral hypoglycaemic agents) may cause an increased blood glucose lowering effect with risk of hypoglycaemia. This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment.

Co-trimoxazole (trimethoprim/sulfamethoxazole)

Patients taking concomitant co-trimoxazole (trimethoprim/sulfamethoxazole) may be at increased risk of hyperkalaemia (see section 4.4).

Acetylsalicylic acid, thrombolytics, beta-blockers, nitrates

Lisinopril tablets may be used concomitantly with acetylsalicylic acid (at cardiologic doses), thrombolytics, beta-blockers and/or nitrates.

Pregnancy

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.

Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (See section 5.3.). Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension (see sections 4.3 and 4.4).

Breast-feedingBecause no information is available regarding the use of Lisinopril tablet during breastfeeding, Lisinopril tablet is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or tiredness may occur.

The following undesirable effects have been observed and reported during treatment with Lisinopril tablets and other ACE inhibitors with the following frequencies: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Safety data from clinical studies suggest that lisinopril is generally well tolerated in hypertensive paediatric patients, and that the safety profile in this age group is comparable to that seen in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

Limited data are available for overdose in humans. Symptoms associated with overdosage of ACE inhibitors may include hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

The recommended treatment of overdose is intravenous infusion of normal saline solution. If hypotension occurs, the patient should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered. If ingestion is recent, take measures aimed at eliminating Lisinopril tablets (e.g., emesis, gastric lavage, administration of absorbents and sodium sulphate). Lisinopril tablets may be removed from the general circulation by haemodialysis (see section 4.4). Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored frequently.

Pharmacotherapeutic group: Angiotensin converting enzyme inhibitors, ATC code: C09A A03

Mechanism of Action

Lisinopril tablets is a peptidyl dipeptidase inhibitor. It inhibits the angiotensin converting enzyme (ACE) that catalyses the conversion of angiotensin I to the vasoconstrictor peptide, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased concentrations of angiotensin II which results in decreased vasopressor activity and reduced aldosterone secretion. The latter decrease may result in an increase in serum potassium concentration.

Pharmacodynamic effects

Whilst the mechanism through which lisinopril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, lisinopril is antihypertensive even in patients with low renin hypertension. ACE is identical to kininase II, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodilatory peptide, play a role in the therapeutic effects of lisinopril remains to be elucidated.

Clinical efficacy and safety

The effect of Lisinopril tablets on mortality and morbidity in heart failure has been studied by comparing a high dose (32.5 mg or 35 mg once daily) with a low dose (2.5 mg or 5 mg once daily). In a study of 3164 patients, with a median follow up period of 46 months for surviving patients, high dose Lisinopril tablets produced a 12% risk reduction in the combined endpoint of all-cause mortality and all-cause hospitalisation (p = 0.002) and an 8% risk reduction in all-cause mortality and cardiovascular hospitalisation (p = 0.036) compared with low dose. Risk reductions for all-cause mortality (8%; p = 0.128) and cardiovascular mortality (10%; p = 0.073) were observed. In a post-hoc analysis, the number of hospitalisations for heart failure was reduced by 24% (p=0.002) in patients treated with high-dose Lisinopril tablets compared with low dose. Symptomatic benefits were similar in patients treated with high and low doses of Lisinopril tablets.

The results of the study showed that the overall adverse event profiles for patients treated with high or low dose Lisinopril tablets were similar in both nature and number. Predictable events resulting from ACE inhibition, such as hypotension or altered renal function, were manageable and rarely led to treatment withdrawal. Cough was less frequent in patients treated with high dose Lisinopril tablets compared with low dose.

In the GISSI-3 trial, which used a 2×2 factorial design to compare the effects of Lisinopril tablets and glyceryl trinitrate given alone or in combination for 6 weeks versus control in 19,394, patients who were administered the treatment within 24 hours of an acute myocardial infarction, Lisinopril tablets produced a statistically significant risk reduction in mortality of 11% versus control (2p=0.03). The risk reduction with glyceryl trinitrate was not significant but the combination of Lisinopril tablets and glyceryl trinitrate produced a significant risk reduction in mortality of 17% versus control (2p=0.02). In the sub-groups of elderly (age > 70 years) and females, pre-defined as patients at high risk of mortality, significant benefit was observed for a combined endpoint of mortality and cardiac function. The combined endpoint for all patients, as well as the high-risk sub-groups, at 6 months also showed significant benefit for those treated with Lisinopril tablets or Lisinopril tablets plus glyceryl trinitrate for 6 weeks, indicating a prevention effect for Lisinopril tablets. As would be expected from any vasodilator treatment, increased incidences of hypotension and renal dysfunction were associated with Lisinopril tablets treatment but these were not associated with a proportional increase in mortality.

In a double-blind, randomised, multicentre trial which compared Lisinopril tablets with a calcium channel blocker in 335 hypertensive Type 2 diabetes mellitus subjects with incipient nephropathy characterised by microalbuminuria, Lisinopril tablets 10 mg to 20 mg administered once daily for 12 months, reduced systolic/diastolic blood pressure by 13/10 mmHg and urinary albumin excretion rate by 40%. When compared with the calcium channel blocker, which produced a similar reduction in blood pressure, those treated with Lisinopril tablets showed a significantly greater reduction in urinary albumin excretion rate, providing evidence that the ACE inhibitory action of Lisinopril tablets reduced microalbuminuria by a direct mechanism on renal tissues in addition to its blood pressure lowering effect.

Lisinopril treatment does not affect glycaemic control as shown by a lack of significant effect on levels of glycated haemoglobin (HbA_1c).

Renin-angiotensin system (RAS)-acting agents

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an angiotensin II receptor blocker.

ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.

These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers.

ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in patients with diabetic nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the placebo group.

Paediatric population

In a clinical study involving 115 paediatric patients with hypertension, aged 6-16 years, patients who weighed less than 50 kg received either 0.625 mg, 2.5 mg or 20 mg of lisinopril once a day, and patients who weighed 50 kg or more received either 1.25 mg, 5 mg or 40 mg of lisinopril once a day. At the end of 2 weeks, lisinopril administered once daily lowered trough blood pressure in a dose-dependent manner with a consistent antihypertensive efficacy demonstrated at doses greater than 1.25 mg.

This effect was confirmed in a withdrawal phase, where the diastolic pressure rose by about 9 mm Hg more in patients randomized to placebo than it did in patients who were randomized to remain on the middle and high doses of lisinopril. The dose-dependent antihypertensive effect of lisinopril was consistent across several demographic subgroups: age, Tanner stage, gender, and race.

Lisinopril is an orally active non-sulphydryl-containing ACE inhibitor.

Absorption

Following oral administration of lisinopril, peak serum concentrations occur within about 7 hours, although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. Based on urinary recovery, the mean extent of absorption of lisinopril is approximately 25% with inter-patient variability of 6-60% over the dose range studied (5-80 mg). The absolute bioavailability is reduced approximately 16% in patients with heart failure. Lisinopril absorption is not affected by the presence of food.

Distribution

Lisinopril does not appear to be bound to serum proteins other than to circulating angiotensin converting enzyme (ACE). Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly.

Elimination

Lisinopril does not undergo metabolism and is excreted entirely unchanged into the urine. On multiple dosing lisinopril has an effective half-life of accumulation of 12.6 hours. The clearance of lisinopril in healthy subjects is approximately 50 ml/min. Declining serum concentrations exhibit a prolonged terminal phase, which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose.

Hepatic impairment

Impairment of hepatic function in cirrhotic patients resulted in a decrease in lisinopril absorption (about 30% as determined by urinary recovery) but an increase in exposure (approximately 50%) compared to healthy subjects due to decreased clearance.

Renal impairment

Impaired renal function decreases elimination of lisinopril, which is excreted via the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 ml/min. In mild to moderate renal impairment (creatinine clearance 30-80 ml/min) mean AUC was increased by 13% only, while a 4.5-fold increase in mean AUC was observed in severe renal impairment (creatinine clearance 5-30 ml/min).

Lisinopril can be removed by dialysis. During 4 hours of haemodialysis, plasma lisinopril concentrations decreased on average by 60%, with a dialysis clearance between 40 and 55 ml/min.

Heart failure

Patients with heart failure have a greater exposure of lisinopril when compared to healthy subjects (an increase in AUC on average of 125%), but based on the urinary recovery of lisinopril, there is reduced absorption of approximately 16% compared to healthy subjects.

Paediatric population

The pharmacokinetic profile of lisinopril was studied in 29 paediatric hypertensive patients, aged between 6 and 16 years, with a GFR above 30 ml/min/1.73m². After doses of 0.1 to 0.2 mg/kg, steady state peak plasma concentrations of lisinopril occurred within 6 hours, and the extent of absorption based on urinary recovery was about 28%. These values are similar to those obtained previously in adults.

AUC and C_max values in children in this study were consistent with those observed in adults.

Elderly

Elderly have higher blood levels and higher values for the area under the plasma concentration time curve (increased approximately 60%) compared with younger subjects.

Preclinical data reveal no special hazard for humans based on conventional studies of general pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential. Angiotensin converting enzyme inhibitors, as a class, have been shown to induce adverse effects on the late foetal development, resulting in foetal death and congenital effects, in particular affecting the skull. Foetotoxicity, intrauterine growth retardation and patent ductus arteriosus have also been reported. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the foetal renin-angiotensin system and partly due to ischaemia resulting from maternal hypotension and decreases in foetal-placental blood flow and oxygen/nutrients delivery to the foetus.

Mannitol

Calcium hydrogen phosphate dihydrate

Maize starch

Starch, pregelatinised

Magnesium stearate

Silica, colloidal anhydrous

Do not store above 30°C.

Carton containing 14, 28, 30 or 98 tablets in transparent PVC/PVDC/Aluminium blisters.

Not all pack sizes may be marketed.

The easiest way to break the tablet is illustrated below:

– place the tablet with the score on top

– place thumb and index of the same hand on each side of the score line and press as shown on the drawing.

Any unused product or waste material should be disposed of in accordance with local requirements

Accord Healthcare Limited

319 Pinner Road

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Middlesex HA1 4HF

United Kingdom

Lisinopril 2.5mg Tablets – Summary of Product Characteristics (SmPC)

This information is intended for use by health professionals

Each tablet contains Lisinopril 2.5mg as Lisinopril dihydrate.

For excipients see section 6.1

Tablet.

White, Circular, biconvex 6mm tablets.

Hypertension

Treatment of hypertension.

Heart failure

Treatment of symptomatic heart failure.

Acute myocardial infarction

Short-term (6 weeks) treatment of haemodynamically stable patients within 24 hours of an acute myocardial infarction.

Renal complications of diabetes mellitus

Treatment of renal disease in hypertensive patients with Type 2 diabetes mellitus and incipient nephropathy (see section 5.1)

Posology

.

Lisinopril Tablets should be administered orally in a single daily dose. As with all other medication taken once daily, Lisinopril should be taken at approximately the same time each day. The absorption of Lisinopril Tablets is not affected by food.

The dose should be individualised according to patient profile and blood pressure response (see section 4.4).

Hypertension

Lisinopril may be used as monotherapy or in combination with other classes of antihypertensive therapy (see sections 4.3, 4.4, 4.5 and 5.1).

Starting dose

In patients with hypertension the usual recommended starting dose is 10 mg. Patients with a strongly activated reninangiotensin- aldosterone system (in particular, renovascular hypertension, salt and /or volume depletion, cardiac decompensation, or severe hypertension) may experience an excessive blood pressure fall following the initial dose. A starting dose of 2.5-5 mg is recommended in such patients and the initiation of treatment should take place under medical supervision. A lower starting dose is required in the presence of renal impairment (see Table 1 below).

Maintenance dose

The usual effective maintenance dosage is 20 mg administered in a single daily dose. In general, if the desired therapeutic effect cannot be achieved in a period of 2 to 4 weeks on a certain dose level, the dose can be further increased. The maximum dose used in long-term, controlled clinical trials was 80 mg/day.

Diuretic-treated patients

Symptomatic hypotension may occur following initiation of therapy with Lisinopril. This is more likely in patients who are being treated currently with diuretics. Caution is recommended therefore, since these patients may be volume and/or salt depleted. If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with Lisinopril. In hypertensive patients in whom the diuretic cannot be discontinued, therapy with Lisinopril should be initiated with a 5 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of Lisinopril should be adjusted according to blood pressure response. If required, diuretic therapy may be resumed (see section 4.4 and 4.5).

Dosage adjustment in renal impairment

Dosage in patients with renal impairment should be based on creatinine clearance as outlined in Table 1 below.

Table 1 Dosage adjustment in renal impairment

* Dosage and/or frequency of administration should be adjusted depending on the blood pressure response.

The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.

Use in Hypertensive Paediatric Patients aged 6-16 years:

The recommended initial dose is 2.5 mg once daily in patients 20 to <50 kg, and 5 mg once daily in patients ≥50 kg. The dosage should be individually adjusted to a maximum of 20 mg daily in patients weighing 20 to <50 kg, and 40 mg in patients ≥50 kg. Doses above 0.61 mg/kg (or in excess of 40 mg) have not been studied in paediatric patients (see section 5.1).

In children with decreased renal function, a lower starting dose or increased dosing interval should be considered.

Heart Failure

In patients with symptomatic heart failure, Lisinopril should be used as adjunctive therapy to diuretics and, where appropriate, digitalis or beta-blockers. Lisinopril may be initiated at a starting dose of 2.5 mg once a day, which should be administered under medical supervision to determine the initial effect on the blood pressure. The dose of Lisinopril should be increased:

• By increments of no greater than 10 mg

• At intervals of no less than 2 weeks

• To the highest dose tolerated by the patient up to a maximum of 35 mg once daily.

Dose adjustment should be based on the clinical response of individual patients.

Patients at high risk of symptomatic hypotension, e.g. patients with salt depletion with or without hyponatraemia, patients with hypovolaemia or patients who have been receiving vigorous diuretic therapy should have these conditions corrected, if possible, prior to therapy with Lisinopril. Renal function and serum potassium should be monitored (see section 4.4).

Posology in Acute myocardial infarction

Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin, and beta-blockers. Intravenous or transdermal glyceryl trinitrate may be used together with Lisinopril.

Starting dose (first 3 days after infarction)

Treatment with Lisinopril may be started within 24 hours of the onset of symptoms. Treatment should not be started if systolic blood pressure is lower than 100 mmHg. The first dose of Lisinopril is 5mg given orally, followed by 5mg after 24 hours, 10mg after 48 hours and then 10mg once daily. Patients with a low systolic blood pressure (120 mmHg or less) when treatment is started or during the first 3 days after the infarction should be given a lower dose – 2.5mg orally (see section 4.4).

In cases of renal impairment (creatinine clearance <80ml/min), the initial Lisinopril dosage should be adjusted according to the patient’s creatinine clearance (see Table 1).

Maintenance dose

The maintenance dose is 10 mg once daily. If hypotension occurs (systolic blood pressure less than or equal to 100 mmHg), a daily maintenance dose of 5mg may be given with temporary reductions to 2.5mg if needed. If prolonged hypotension occurs (systolic blood pressure less than 90 mmHg for more than 1 hour), Lisinopril should be withdrawn.

Treatment should continue for 6 weeks and then the patient should be re-evaluated. Patients who develop symptoms of heart failure should continue with Lisinopril (see section 4.2).

Renal complications of diabetes mellitus

In hypertensive patients with type 2 diabetes mellitus and incipient nephropathy, the dose is 10 mg Lisinopril once daily which can be increased to 20 mg once daily, if necessary, to achieve a sitting diastolic blood pressure below 90 mm Hg.

In cases of renal impairment (creatinine clearance <80 ml/min), the initial Lisinopril dosage should be adjusted according to the patient’s creatinine clearance (see Table 1).

Paediatric population

There is limited efficacy and safety experience in hypertensive children >6 years old, but no experience in other indications (see section 5.1). Lisinopril is not recommended in children in other indications than hypertension.

Lisinopril is not recommended in children below the age of 6, or in children with severe renal impairment (GFR <30ml/min/1.73m²) (see section 5.2).

Elderly

In clinical studies, there was no age-related change in the efficacy or safety profile of the drug. When advanced age is associated with decrease in renal function, however, the guidelines set out in Table 1 should be used to determine the starting dose of Lisinopril. Thereafter, the dosage should be adjusted according to the blood pressure response.

Use in kidney transplant patients

There is no experience regarding the administration of Lisinopril in patients with recent kidney transplantation. Treatment with Lisinopril is therefore not recommended.

Method of administration:

Oral.

• Hypersensitivity to Lisinopril, to any of the excipients listed in section 6.1 or any other angiotensin converting enzyme (ACE) inhibitor

• History of angioedema associated with previous ACE inhibitor therapy

Concomitant use of Lisinopril with sacubitril/valsartan therapy. Lisinopril must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.4 and 4.5).

• Hereditary or idiopathic angioedema

• Second and third trimesters of pregnancy (see sections 4.4 and 4.6)

• The concomitant use of Lisinopril with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m² (see sections 4.5 and 5.1).

Symptomatic hypotension

Symptomatic hypotension is seen rarely in uncomplicated hypertensive patients. In hypertensive patients receiving Lisinopril, hypotension is more likely to occur if the patient has been volume-depleted, e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting, or has severe renin-dependent hypertension (see section 4.5 and section 4.8). In patients with heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be closely monitored. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.

In some patients with heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with Lisinopril. This effect is anticipated and is not usually a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose or discontinuation of Lisinopril may be necessary.

Hypotension in acute myocardial infarction

Treatment with Lisinopril must not be initiated in acute myocardial infarction patients who are at risk of further serious haemodynamic deterioration after treatment with a vasodilator. These are patients with systolic blood pressure of 100 mm Hg or lower, or those in cardiogenic shock. During the first 3 days following the infarction, the dose should be reduced if the systolic blood pressure is 120 mm Hg or lower. Maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg if systolic blood pressure is 100 mmHg or lower. If hypotension persists (systolic blood pressure less than 90 mm Hg for more than 1 hour) then Lisinopril should be withdrawn.

Aortic and mitral valve stenosis / hypertrophic cardiomyopathy

As with other ACE inhibitors, Lisinopril should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy.

Renal function impairment

In cases of renal impairment (creatinine clearance <80 ml/min), the initial Lisinopril dosage should be adjusted according to the patient’s creatinine clearance (see Table 1 in section 4.2), and then as a function of the patient’s response to treatment. Routine monitoring of potassium and creatinine is part of normal medical practice for these patients.

In patients with heart failure, hypotension following the initiation of therapy with ACE inhibitors may lead to some further impairment in renal function. Acute renal failure, usually reversible, has been reported in this situation.

In some patients with bilateral renal artery stenosis or with a stenosis of the artery to a solitary kidney, who have been treated with angiotensin-converting enzyme inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen. This is especially likely in patients with renal insufficiency. If renovascular hypertension is also present there is an increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started under close medical supervision with low doses and careful dose titration. Since treatment with diuretics may be a contributory factor to the above, they should be discontinued and renal function should be monitored during the first weeks of Lisinopril therapy.

Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when Lisinopril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or Lisinopril may be required.

In acute myocardial infarction, treatment with Lisinopril should not be initiated in patients with evidence of renal dysfunction, defined as serum creatinine concentration exceeding 177 micromol/l and/or proteinuria exceeding 500 mg/24 h. If renal dysfunction develops during treatment with Lisinopril (serum creatinine concentration exceeding 265 micromol/l or a doubling from the pre-treatment value) then the physician should consider withdrawal of Lisinopril.

Hypersensitivity/Angioedema

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely in patients treated with angiotensin-converting enzyme inhibitors, including Lisinopril. This may occur at any time during therapy. In such cases, Lisinopril should be discontinued promptly and appropriate treatment and monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patients. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient.

Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema. Patients with involvement of the tongue, glottis or larynx, are likely to experience airway obstruction, especially those with a history of airway surgery. In such cases emergency therapy should be administered promptly. This may include the administration of adrenaline and/or the maintenance of a patent airway. The patient should be under close medical supervision until complete and sustained resolution of symptoms has occurred.

Angiotensin-converting enzyme inhibitors cause a higher rate of angioedema in black patients than in non-black patients.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see section 4.3).

Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to the increased risk of angioedema. Treatment with sacubitril/valsartan must not be initiated earlier than 36 hours after the last dose of Lisinopril. Treatment with Lisinopril must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5).

Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin may lead to an increased risk of angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment) (see section 4.5). Caution should be used when starting racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin in a patient already taking an ACE inhibitor.

Anaphylactoid reactions in haemodialysis patients

Anaphylactoid reactions have been reported in patients dialysed with high flux membranes (e.g. AN 69) and treated concomitantly with an ACE inhibitor. In these patients, consideration should be given to using a different type of dialysis membrane or different class of antihypertensive agent.

Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis

Rarely, patients receiving ACE inhibitors during low-density lipoproteins (LDL) apheresis with dextran sulphate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.

Desensitisation

Patients receiving ACE inhibitors during desensitisation treatment (e.g. hymenoptera venom) have sustained anaphylactoid reactions. In the same patients, these reactions have been avoided when ACE inhibitors were temporarily withheld but they have reappeared upon inadvertent re-administration of the medicinal product.

Hepatic failure

Very rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving Lisinopril who develop jaundice or marked elevations of hepatic enzymes should discontinue Lisinopril and receive appropriate medical follow-up.

Neutropenia/Agranulocytosis

Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia occurs rarely. Neutropenia and agranulocytosis are reversible after discontinuation of the ACE inhibitor. Lisinopril should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function. Some of these patients developed serious infections, which in a few instances did not respond to intensive antibiotic therapy. If Lisinopril is used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).

If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Race

Angiotensin-converting enzyme inhibitors cause a higher rate of angioedema in black patients than in non-black patients.

As with other ACE inhibitors, Lisinopril may be less effective in lowering blood pressure in black patients than in non-blacks, possibly because of a higher prevalence of low-renin states in the black hypertensive population.

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

Surgery/anaesthesia

In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, Lisinopril may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Hyperkalaemia

ACE inhibitors can cause hyperkalemia because they inhibit the release of aldosterone. The effect is usually not significant in patients with normal renal function. However, in patients with impaired renal function, diabetes mellitus and/or in patients taking potassium supplements (including salt substitutes), potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), other drugs associated with increase in serum potassium (e.g. heparin, trimethoprim or co-trimoxazole also known as trimethoprim/sulfamethoxazole) and especially aldosterone antagonists or angiotensin-receptor blockers, hyperkalemia can occur. Potassium-sparing diuretics and angiotensin-receptor blockers should be used with caution in patients receiving ACE inhibitors, and serum potassium and renal function should be monitored (see section 4.5).

Diabetic patients

In diabetic patients treated with oral antidiabetic agents or insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor (see 4.5 Interaction with other medicinal products and other forms of interaction).

Lithium

The combination of lithium and Lisinopril is generally not recommended (see section 4.5).

Pregnancy

ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

Antihypertensive agents

When Lisinopril is combined with other antihypertensive agents (e.g. glyceryl trinitrate and other nitrates, or other vasodilators), additive falls in blood pressure may occur.

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1).

Medicines increasing the risk of angioedema

Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated as this increases the risk of angioedema (see section 4.3 and 4.4).

Concomitant treatment of ACE inhibitors with mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus, sirolimus, everolimus) or neutral endopeptidase (NEP) inhibitors (e.g. racecadotril), vildagliptin or tissue plasminogen activator may increase the risk of angioedema (see section 4.4).

Diuretics

When a diuretic is added to the therapy of a patient receiving Lisinopril the antihypertensive effect is usually additive.

Patients already on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure when Lisinopril is added. The possibility of symptomatic hypotension with Lisinopril can be minimised by discontinuing the diuretic prior to initiation of treatment with Lisinopril (see section 4.4 and section 4.2).

Potassium supplements, potassium-sparing diuretics or potassium-containing salt substitutes and other drugs that may increase serum potassium levels

Although serum potassium usually remains within normal limits, hyperkalaemia may occur in some patients treated with Lisinopril. Use of potassium sparing diuretics (e.g. spironolactone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, particularly in patients with impaired renal function, may lead to a significant increase in serum potassium. Care should also be taken when Lisinopril is coadministered with other agents that increase serum potassium, such as trimethoprim and co-trimoxazole (trimethoprim/sulfamethoxazole) as trimethoprim is known to act as a potassium-sparing diuretic like amiloride. Therefore, the combination of Lisinopril with the above-mentioned drugs is not recommended. If concomitant use is indicated, they should be used with caution and with frequent monitoring of serum potassium. If Lisinopril is given with a potassium-losing diuretic, diuretic-induced hypokalaemia may be ameliorated.

Ciclosporin

Hyperkalaemia may occur during concomitant use of ACE inhibitors with ciclosporin. Monitoring of serum potassium is recommended.

Heparin

Hyperkalaemia may occur during concomitant use of ACE inhibitors with heparin. Monitoring of serum potassium is recommended.

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Concomitant use of thiazide diuretics may increase the risk of lithium toxicity and enhance the already increased lithium toxicity with ACE inhibitors. Use of Lisinopril with lithium is not recommended, but if the combination proves necessary, careful monitoring of serum lithium levels should be performed (see section 4.4).

Non-steroidal anti-inflammatory medicinal products (NSAIDs) including acetylsalicylic acid ≥ 3 g/day

When ACE-inhibitors are administered simultaneously with non-steroidal anti-inflammatory drugs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs), attenuation of the antihypertensive effect may occur. Concomitant use of ACE-inhibitors and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. These effects are usually reversible. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.

Gold

Nitritoid reactions (symptoms of vasodilatation including flushing, nausea, dizziness and hypotension, which can be very severe) following injectable gold (for example, sodium aurothiomalate) have been reported more frequently in patients receiving ACE inhibitor therapy.

Tricyclic antidepressants / Antipsychotics / Anaesthetics

Concomitant use of certain anaesthetic medicinal products, tricyclic antidepressants and antipsychotics with ACE inhibitors may result in further reduction of blood pressure (see section 4.4).

Sympathomimetics

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.

Antidiabetics

Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicines (insulins, oral hypoglycaemic agents) may cause an increased blood glucose-lowering effect with risk of hypoglycaemia. This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment.

.

Acetylsalicylic acid, thrombolytics, beta-blockers, nitrates

Lisinopril may be used concomitantly with acetylsalicylic acid (at cardiologic doses), thrombolytics, beta-blockers and/or nitrates.

Pregnancy

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.

Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (See section 5.3.).

Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.

Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension (see sections 4.3 and 4.4).

Breastfeeding

Because no information is available regarding the use of lisinopril during breastfeeding, lisinopril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or tiredness may occur.

The following undesirable effects have been observed and reported during treatment with Lisinopril and other ACE inhibitors with the following frequencies: Very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Blood and the lymphatic system disorders

rare: decreases in haemoglobin, decreases in haematocrit

very rare: bone marrow depression, anaemia, thrombocytopenia, leucopenia, neutropenia, agranulocytosis (see section 4.4), haemolytic anaemia, lymphadenopathy, autoimmune disease

Immune system disorders

not known: anaphylactic/anaphylactoid reaction

Metabolism and nutrition disorders

very rare: hypoglycaemia

Nervous system and psychiatric disorders

common: dizziness, headache

uncommon: mood alterations, paraesthesia, vertigo, taste disturbance, sleep disturbances, hallucinations

rare: mental confusion, olfactory disturbance

frequency not known: depressive symptoms, syncope

Cardiac and vascular disorders

common: orthostatic effects (including hypotension)

uncommon: myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients (see section 4.4), palpitations, tachycardia, Raynaud’s phenomenon

Respiratory, thoracic and mediastinal disorders

common: cough

uncommon: rhinitis

very rare: bronchospasm, sinusitis, allergic alveolitis/eosinophilic pneumonia

Gastrointestinal disorders

common: diarrhoea, vomiting

uncommon: nausea, abdominal pain and indigestion

rare: dry mouth

very rare: pancreatitis, intestinal angioedema, hepatitis – either hepatocellular or cholestatic, jaundice and hepatic failure (see section 4.4)

Skin and subcutaneous tissue disorders

uncommon: rash, pruritus

rare: urticaria, alopecia, psoriasis, hypersensitivity/angioneurotic oedema: angioneurotic oedema of the face, extremities, lips, tongue, glottis, and/or larynx (see section 4.4)

very rare: sweating, pemphigus, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme, cutaneous pseudolymphoma

A symptom complex has been reported which may include one or more of the following: fever, vasculitis, myalgia, arthralgia/arthritis, positive antinuclear antibodies (ANA), elevated red blood cell sedimentation rate (ESR), eosinophilia and leucocytosis, rash, photosensitivity or other dermatological manifestations may occur.

Renal and urinary disorders

common: renal dysfunction

rare: uraemia, acute renal failure

very rare: oliguria/anuria

Endocrine disorders

rare: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Reproductive system and breast disorders

uncommon: impotence

rare: gynaecomastia

General disorders and administration site conditions

uncommon: fatigue, asthenia

Investigations

uncommon: increases in blood urea, increases in serum creatinine, increases in liver enzymes, hyperkalaemia

rare: increases in serum bilirubin, hyponatraemia

Safety data from clinical studies suggest that lisinopril is generally well tolerated in hypertensive paediatric patients, and that the safety profile in this age group is comparable to that seen in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Limited data are available for overdose in humans. Symptoms associated with overdosage of ACE inhibitors may include hypotension, circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

The recommended treatment of overdose is intravenous infusion of normal saline solution. If hypotension occurs, the patient should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered. If ingestion is recent, take measures aimed at eliminating Lisinopril (e.g. emesis, gastric lavage, administration of absorbents and sodium sulphate). Lisinopril may be removed from the general circulation by haemodialysis (see section 4.4). Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored frequently.

Pharmacotherapeutic group: Angiotensin-converting enzyme inhibitors, ATC Code: C09A A03

Mechanism of Action

Lisinopril is a peptidyl dipeptidase inhibitor. It inhibits the angiotensin-converting enzyme (ACE) that catalyses the conversion of angiotensin I to the vasoconstrictor peptide, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased concentrations of angiotensin II which results in decreased vasopressor activity and reduced aldosterone secretion. The latter decrease may result in an increase in serum potassium concentration.

Pharmacodynamic effects

Whilst the mechanism through which Lisinopril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, Lisinopril is antihypertensive even in patients with low renin hypertension. ACE is identical to Kinase II, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodilatory peptide, play a role in the therapeutic effect of Lisinopril remains to be elucidated.

Clinical efficacy and safety

The effect of Lisinopril on mortality and morbidity in heart failure has been studied by comparing a high dose (32.5 mg or 35 mg once daily) with a low dose (2.5 mg or 5 mg once daily). In a study of 3164 patients, with a median follow-up period of 46 months for surviving patients, high dose Lisinopril produced a 12% risk reduction in the combined endpoint of all-cause mortality and all-cause hospitalisation (p = 0.002) and an 8% risk reduction in all-cause mortality and cardiovascular hospitalisation (p = 0.036) compared with low dose. Risk reductions for all-cause mortality (8%; p = 0.128) and cardiovascular mortality (10%; p = 0.073) were observed. In a post-hoc analysis, the number of hospitalisations for heart failure was reduced by 24% (p=0.002) in patients treated with high-dose Lisinopril compared with low dose. Symptomatic benefits were similar in patients treated with high and low doses of Lisinopril.

The results of the study showed that the overall adverse event profiles for patients treated with high or low dose Lisinopril were similar in both nature and number. Predictable events resulting from ACE inhibition, such as hypotension or altered renal function, were manageable and rarely led to treatment withdrawal. Cough was less frequent in patients treated with high dose Lisinopril compared with low dose.

In the GISSI-3 trial, which used a 2×2 factorial design to compare the effects of Lisinopril and glyceryl trinitrate given alone or in combination for 6 weeks versus control in 19,394 patients who were administered the treatment within 24 hours of an acute myocardial infarction, Lisinopril produced a statistically significant risk reduction in mortality of 11% versus control (2p=0.03). The risk reduction with glyceryl trinitrate was not significant but the combination of Lisinopril and glyceryl trinitrate produced a significant risk reduction in mortality of 17% versus control (2p=0.02). In the sub-groups of elderly (age > 70 years) and females, pre-defined as patients at high risk of mortality, significant benefit was observed for a combined endpoint of mortality and cardiac function. The combined endpoint for all patients, as well as the high-risk sub-groups at 6 months, also showed significant benefit for those treated with Lisinopril or Lisinopril plus glyceryl trinitrate for 6 weeks, indicating a prevention effect for Lisinopril. As would be expected from any vasodilator treatment, increased incidences of hypotension and renal dysfunction were associated with Lisinopril treatment but these were not associated with a proportional increase in mortality.

In a double-blind, randomised, multicentre trial which compared Lisinopril with a calcium channel blocker in 335 hypertensive Type 2 diabetes mellitus subjects with incipient nephropathy characterised by microalbuminuria, Lisinopril 10 mg to 20 mg administered once daily for 12 months, reduced systolic/diastolic blood pressure by 13/10 mmHg and urinary albumin excretion rate by 40%. When compared with the calcium channel blocker, which produced a similar reduction in blood pressure, those treated with Lisinopril showed a significantly greater reduction in urinary albumin excretion rate, providing evidence that the ACE inhibitory action of Lisinopril reduced microalbuminuria by a direct mechanism on renal tissues in addition to its blood pressure-lowering effect.

Lisinopril treatment does not affect glycaemic control as shown by a lack of significant effect on levels of glycated haemoglobin (HbA_1c).

Renin-angiotensin system (RAS)-acting agents

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an angiotensin II receptor blocker.

ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.

These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers.

ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in patients with diabetic nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the placebo group.

Paediatric population

In a clinical study involving 115 paediatric patients with hypertension, aged 6-16 years, patients who weighed less than 50 kg received either 0.625 mg, 2.5 mg or 20 mg of lisinopril once a day, and patients who weighed 50 kg or more received either 1.25 mg, 5 mg or 40 mg of lisinopril once a day. At the end of 2 weeks, lisinopril administered once daily lowered trough blood pressure in a dose-dependent manner with a consistent antihypertensive efficacy demonstrated at doses greater than 1.25 mg.

This effect was confirmed in a withdrawal phase, where the diastolic pressure rose by about 9 mm Hg more in patients randomized to placebo than it did in patients who were randomized to remain on the middle and high doses of lisinopril. The dose-dependent antihypertensive effect of lisinopril was consistent across several demographic subgroups: age, Tanner stage, gender, and race.

Lisinopril is an orally active non-sulphydryl-containing ACE inhibitor.

Absorption

Following oral administration of lisinopril, peak serum concentrations occur within about 7 hours, although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. Based on urinary recovery, the mean extent of absorption of lisinopril is approximately 25% with interpatient variability of 6-60% over the dose range studied (5-80 mg). The absolute bioavailability is reduced approximately 16% in patients with heart failure. Lisinopril absorption is not affected by the presence of food.

Distribution

Lisinopril does not appear to be bound to serum proteins other than to circulating angiotensin-converting enzyme (ACE). Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly.

Elimination

Lisinopril does not undergo metabolism and is excreted entirely unchanged into the urine. On multiple dosing, Lisinopril has an effective half-life of accumulation of 12.6 hours. The clearance of lisinopril in healthy subjects is approximately 50 ml/min. Declining serum concentrations exhibit a prolonged terminal phase, which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose.

Hepatic impairment

Impairment of hepatic function in cirrhotic patients resulted in a decrease in lisinopril absorption (about 30% as determined by urinary recovery), but an increase in exposure (approximately 50%) compared to healthy subjects due to decreased clearance.

Renal impairment

Impaired renal function decreases elimination of lisinopril, which is excreted via the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 ml/min. In mild to moderate renal impairment (creatinine clearance 30-80 ml/min), mean AUC was increased by 13% only, while a 4.5- fold increase in mean AUC was observed in severe renal impairment (creatinine clearance 5-30 ml/min).

Lisinopril can be removed by dialysis. During 4 hours of haemodialysis, plasma lisinopril concentrations decreased on average by 60%, with a dialysis clearance between 40 and 55 ml/min.

Heart failure

Patients with heart failure have a greater exposure of lisinopril when compared to healthy subjects (an increase in AUC on average of 125%), but based on the urinary recovery of lisinopril, there is reduced absorption of approximately 16% compared to healthy subjects.

Paediatric population

The pharmacokinetic profile of lisinopril was studied in 29 paediatric hypertensive patients, aged between 6 and 16 years, with a GFR above 30 ml/min/1.73m2. After doses of 0.1 to 0.2 mg/kg, steady state peak plasma concentrations of lisinopril occurred within 6 hours, and the extent of absorption based on urinary recovery was about 28%.These values are similar to those obtained previously in adults.

AUC and C_max values in children in this study were consistent with those observed in adults.

Elderly

Elder patients have higher blood levels and higher values for the area under the plasma concentration-time curve (increased approximately 60%) compared with younger subjects.

Preclinical data reveal no special hazard for humans based on conventional studies of general pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential. Angiotensin-converting enzyme inhibitors, as a class, have been shown to induce adverse effects on the late foetal development, resulting in foetal death and congenital effects, in particular affecting the skull. Foetotoxicity, intrauterine growth retardation and patent ductus arteriosus have also been reported. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the foetal renin-angiotensin system and partly due to ischaemia resulting from maternal hypotension and decreases in foetal placental blood flow and oxygen/nutrients delivery to the foetus.

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Uses, Side Effects, Dosages, Precautions

Lisinopril (brand names Prinivil and Zestril) is an angiotensin-converting enzyme (ACE) inhibitor. It used to treat hypertension and heart failure. Lisinopril also improves survival when it is taken after a recent heart attack or stroke.

ACE inhibitors cause the blood vessels to dilate (widen), lowering blood pressure. These medications block the activity of ACE, resulting in reduced angiotensin II production in the body. Angiotensin II acts directly on the blood vessels.

Lisinopril is available as an oral (by mouth) tablet as well as a liquid solution. The oral tablets are available in 2.5, 5, 10, 20, and 40 mg tablets. The liquid form of lisinopril must be special ordered by your healthcare provider. Sometimes lisinopril is combined with other blood pressure medications (such as hydrochlorothiazide) to help potentiate its effectiveness. Anxiety is a possible side effect of lisinopril.

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Uses

The Food and Drug Administration (FDA) has approved lisinopril for the treatment of:

• Heart failure
• Hypertension
• Acute (sudden and severe) myocardial Infarction (heart attack)
• High blood pressure in children aged 6 and older

Off-Label Uses

Lisinopril is sometimes used off-label for the treatment of conditions not approved by the Food and Drug Administration (FDA).

Off-label uses for lisinopril include:

Lisinopril is sometimes given for the treatment of kidney disease. Although there have been some clinical research studies to back the effectiveness of lisinopril for some types of kidney disease, such as proteinuric (high amounts of protein in the urine) kidney disease, more studies are needed before the drug will be considered a mainstream medication for the treatment of this condition.

Before Taking Lisinopril

Before giving you a prescription for lisinopril, your healthcare provider will evaluate your blood pressure readings and may do some blood tests to check your kidney function. Your blood potassium level may be checked as well because lisinopril can raise potassium levels.

Before taking lisinopril be sure to tell your healthcare provider if:

• You are taking any other prescription medications, over-the-counter (OTC) medications, vitamins, supplements, or any other type of drugs
• You are pregnant or plan to become pregnant or are breastfeeding
• You have kidney disease
• You have heart problems
• You have been diagnosed with low blood pressure
• You are scheduled for any type of major surgery
• You have had a recent bout of diarrhea or vomiting
• You are on a special diet, such as a low sodium diet
• You have had an allergic reaction to lisinopril
• You plan to have a desensitization treatment for allergies

Lisinopril and Diabetes

Lisinopril may impact your blood sugar, so you may need to check your level more frequently when taking this medication. If you have diabetes, make sure to speak with your healthcare provider.

Other ACE Inhibitors

Other ACE inhibitors include:

• Lotensin (benazepril)        
• Capoten (captopril)
• Vasotec (enalapril) 
• Monopril (fosinopril)         
• Aceon (perindopril) 
• Accupril (quinapril) 
• Altace (ramipril)     
• Mavik (trandolapril)

Ace Inhibitors and Beta-Blockers

Beta-blockers are another medication used to lower blood pressure. One major difference between lisinopril and beta-blockers is that beta-blockers are effective in treating angina (chest pain).

Dosage

Your healthcare provider will prescribe the dosage of lisinopril that is right for you depending on many factors, including the type of medical condition you have—such as high blood pressure or heart failure. Always take lisinopril exactly as instructed by your prescribing healthcare provider.

Average Dosage

The average starting dosage of lisinopril is between 2.5 mg and 10 mg. It is usually to be taken only once per day.

According to the FDA, lisinopril should be started at a low dosage and increased gradually over a time span of several weeks. 

The starting dose depends on the type of medical treatment you are taking lisinopril for, such as:

• High blood pressure: 10 mg one time per day
• Recent heart attack: 5 mg one time per day
• Heart failure: 5 mg one time per day

The maximum dosage of lisinopril is 80 mg one time per day.

Dosages are lower for children and depend on many factors such as the medical condition being treated, the child’s age, weight, and more.

How To Take and Store

How To Take Lisinopril

Lisinopril can be taken with food or on its own. Do not crush the tablet; swallow it whole with liquid. 

If you were prescribed the liquid form, you’ll receive a syringe to help you measure the precise dosage. If you are unsure about how to measure your dosage, be sure to talk to your nurse, the pharmacist, or another healthcare provider.

Proper Measuring Devices

Make sure you are using a proper measuring device for the liquid form of lisinopril. Do not measure it in a regular household measuring tool such as a teaspoon.

How To Store Lisinopril

Storage recommendations for lisinopril include:

• Keep it at room temperature
• Keep it out of the reach of small children
• Protect the bottle from getting wet
• Keep the lid tightly closed
• Throw away any unused tablets or liquid once it has reached its expiration date

Side Effects

Common

Common side effects of lisinopril that do not usually require immediate medical attention (unless they do not go away or are causing discomfort) include:

• A change in the perception of taste
• A cough (sometimes referred to as lisinopril cough)
• Dizziness
• Light sensitivity
• A headache
• A fever
• Anxiety

If your anxiety is severe or does not subside after taking lisinopril for a short time, you should tell your healthcare provider. Abruptly stopping lisinopril suddenly can cause or worsen lisinopril-associated anxiety.

Abruptly discontinuing lisinopril can also cause tachycardia (a fast heart rate) and sweating.

Severe

Severe side effects, that should be reported to your healthcare provider right away, include:

• Dysuria: Problems passing urine, which could be a sign of kidney problems.
• Signs of increased potassium levels: Weakness in the muscles, chest pain, or irregular heart rate.
• Signs of liver problems: Flu-like symptoms, light-colored stools, dark urine, general malaise, upper right abdominal pain, nausea, yellowing of the skin, or in the whites of the eyes.
• Dizziness, feeling faint, lightheadedness, or falling: These are signs of low blood pressure.
• Nausea and vomiting
• An allergic reaction: Including symptoms such as a rash, swelling in the face, lips, throat, hand, feet, or tongue
• Difficulty breathing

This list may not describe every possible side effect of lisinopril. If you experience any other side effects, be sure to contact your healthcare provider. You can also report side effects to the FDA by calling 1-800-FDA-1088.

Lisinopril Warnings and Interactions

Do not stand or sit up suddenly after taking lisinopril, particularly if you are a senior, as this could increase your risk of falls. Do not use heavy machinery or perform any type of activity that requires mental alertness.

Lisinopril should be used with caution in some conditions, including:

• Hyperkalemia (high potassium levels): ACE inhibitors can raise blood potassium levels
• African ancestry: Some studies have found that people of African ancestry do not respond well to ACE inhibitors, also, this population may be more at risk for angioedema, a potentially fatal complication of the drug.

Note, these do not represent all of the warnings for taking lisinopril; be sure to talk with your healthcare provider about any other precautions or warnings linked with ACE inhibitors.

What Is a Black Box Warning?

A black box warning (also referred to as a “boxed warning”), is a serious safety risk associated with a drug.

Lisinopril has a black box warning regarding use during pregnancy. ACE inhibitors (such as lisinopril) can cause injury or even death to the developing fetus during the second or third trimester of pregnancy. If you become pregnant, you need to talk to your doctor about how to discontinue lisinopril as soon as possible.  If you are on lisinopril and you are planning to become pregnant, you should discuss medication changes PRIOR to conceiving,

Precautions and Contraindications

Medications that can interact with lisinopril include:

• Hymenoptera venom (venom from insects used to treat immune-related or inflammatory disease)
• Aliskiren
• Some diabetic medications
• Potassium supplements
• Salt substitute
• NSAIDs should be taken with caution

This list of medications is not all-inclusive, so be sure to provide your healthcare provider with a list of every type of medication you are taking, including the dosage and when you take the drug/s.

Don’t forget to including OTC medications, herbal and natural supplements (including vitamins), and any other type of mediation you take.

Other Contraindications

Other contraindications for lisinopril include:

• Pregnant or breastfeeding mothers
• History of angioedema
• Bilateral renal artery stenosis
• Kidney failure

instructions for use, analogs, articles »Drug Handbook

The most common side effects: dizziness, headache, fatigue, diarrhea, dry cough, nausea.
From the CVS: a marked decrease in blood pressure, chest pain, rarely – orthostatic hypotension, tachycardia, bradycardia, aggravation of symptoms of heart failure, impaired AV conduction, myocardial infarction, heart palpitations.
From the side of the central nervous system: emotional lability, confusion, paresthesia, drowsiness.
From the side of hematopoiesis: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decreased Hb, hematocrit, erythropenia).
Respiratory system: dyspnea, bronchospasm. From the digestive system: dry mouth, anorexia, dyspepsia, taste changes, abdominal pain, pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis.
On the part of the skin: increased sweating, alopecia, photosensitivity.
From the genitourinary system: impaired renal function, oliguria, anuria, acute renal failure, uremia, proteinuria, decreased potency.
Allergic reactions: angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx, skin rashes, urticaria, itching, fever, positive test results for antinuclear antibodies, increased ESR, eosinophilia, leukocytosis, very rarely – intestinal angioedema.
Others: asthenia, myalgia, arthralgia / arthritis, vasculitis, convulsive twitching of the muscles of the limbs and lips.
Laboratory indicators: hyperkalemia, hyponatremia, rarely – increased activity of “liver” enzymes, hyperbilirubinemia, hyper-creatininemia, increased concentration of urea.
Overdose. Symptoms: a marked decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability.
Treatment: symptomatic therapy, intravenous 0.9% NaCl solution, if necessary – vasopressor drugs, control of blood pressure, water-electrolyte balance.
Hemodialysis is effective.

contraindications, side effects, dosages, composition – tablets in the reference book of medicines

Symptomatic hypotension

Most often, a pronounced decrease in blood pressure occurs with a decrease in fluid volume caused by diuretic therapy, a decrease in salt in food, dialysis, diarrhea or vomiting.In patients with chronic heart failure with or without concurrent renal failure, symptomatic hypotension may develop. It was more often detected in patients with severe forms of heart failure, as a result of the use of large doses of a diuretic, hyponatremia, or impaired renal function. In such patients, treatment should be started under the strict supervision of a physician (with caution, select the dose of the drug and diuretics). Similar rules must be followed when prescribing patients with ischemic heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

In case of development of a pronounced decrease in blood pressure, the patient should be placed in the supine position and, if necessary, intravenously injected with 0.9% sodium chloride solution. A transient hypotensive reaction is not a contraindication for taking the next dose of the drug.

When using lisinopril, some patients with chronic heart failure, but with normal or low blood pressure, may experience a decrease in blood pressure, which is usually not a reason for stopping treatment. If arterial hypotension becomes symptomatic, it is necessary to reduce the dose of the drug or stop treatment with lisinopril.

Before starting treatment with lisinopril, if possible, the sodium concentration should be normalized and / or the lost volume of fluid should be replenished, the effect of the initial dose of lisinopril on the patient should be carefully monitored.

Acute myocardial infarction

The use of standard therapy is shown (thrombolytics, acetylsalicylic acid, beta-blockers). Lisinopril can be used with intravenous administration or with the use of nitroglycerin transdermal systems.

Renal dysfunction

As a consequence of inhibition of the renin-angiotensin-aldosterone system, changes in renal function may be expected in patients with individual sensitivity.In patients with severe heart failure, in whom renal function may depend on the activity of the renin-angiotensin-aldosterone system, a pronounced decrease in blood pressure after starting treatment with ACE inhibitors, incl. lisinopril, can lead to further deterioration of renal function, oliguria and / or progressive azotemia, and rarely – to acute renal failure and / or death.

In the case of renal artery stenosis (especially with bilateral stenosis or in the presence of stenosis of an artery of a solitary kidney), as well as in case of circulatory insufficiency due to sodium and / or fluid deficiency, the use of lisinopril can lead to an increase in serum urea and creatinine (usually reversible after discontinuation of treatment), impaired renal function, acute renal failure, which is usually irreversible after discontinuation of the drug.

Hypersensitivity / Angioedema

Angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx was rarely seen in patients treated with an ACE inhibitor, including lisinopril, which can occur at any time during treatment. In this case, treatment with lisinopril should be stopped as soon as possible and the patient should be monitored until the symptoms completely regress. In cases where swelling occurs only on the face and lips, the condition most often goes away without treatment, however, antihistamines may be prescribed.

Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis or larynx are covered, airway obstruction may occur, so appropriate therapy (administration of epinephrine, GCS, antihistamines) and / or measures to ensure airway patency should be given immediately. Patients with a history of antioneurotic edema not associated with previous treatment with ACE inhibitors may be at increased risk of developing it during treatment with an ACE inhibitor.

Anaphylactoid reactions during desensitization on hymenoptera (hymenoptera)

Patients taking ACE inhibitors during desensitization to hymenoptera (hymenoptera) may, extremely rarely, develop an anaphylactoid reaction. This can be avoided by temporarily stopping treatment with an ACE inhibitor before each desensitization.

Patients on hemodialysis

Anaphylactoid reaction was also noted in patients undergoing hemodialysis with a high-flow membrane (for example, AN 69 ^® ), who are simultaneously taking ACE inhibitors.In such cases, consideration should be given to using a different type of dialysis membrane or other antihypertensive drug.

Cough

Cough has been reported with the use of an ACE inhibitor. The cough is dry, prolonged, which disappears after stopping treatment with an ACE inhibitor. In the differential diagnosis of cough, it is necessary to take into account the cough caused by the use of an ACE inhibitor.

Surgery / General Anesthesia

When using drugs that lower blood pressure in patients with major surgery or during anesthesia, lisinopril can block the formation of angiotensin II, secondary to compensatory renin release.

A pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by an increase in BCC.

Potassium

Hyperkalemia has been reported in some cases.

Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus and the simultaneous use of potassium-sparing diuretics (spironolactone, triamterene or amiloride), potassium preparations or salt substitutes containing potassium, especially in patients with impaired renal function.

If the simultaneous use of lisinopril and the above drugs is considered necessary, they should be used with caution, regularly monitoring serum potassium.

Sodium

In patients who are at risk of symptomatic hypotension (on a low-salt or salt-free diet) with or without hyponatremia, as well as in patients who received high doses of diuretics, the above conditions must be compensated (loss of fluid and salts) before starting treatment.

Elderly patients

In elderly patients, the same dose leads to a higher concentration of the drug in the blood, therefore, special care is required in determining the dose, despite the fact that there are no differences in the antihypertensive effect of lisinopril between the elderly and young people.

Control of laboratory parameters

Due to the fact that the potential risk of agranulocytosis cannot be excluded, periodic monitoring of the blood picture is required.

Influence on the ability to drive vehicles and use mechanisms

There is no data on the effect of lisinopril on the ability to drive vehicles and mechanisms, used in therapeutic doses, however, it must be borne in mind that dizziness may occur, therefore caution should be exercised, and the question of the possibility of engaging in potentially hazardous activities should be resolved only after assessing the individual reaction the patient for the drug.

instructions for use, indications, side effects

Pharmacodynamics 90 120
ACE inhibitor, reduces the formation of angiotensin II from angiotensin I.A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the total peripheral vascular resistance, blood pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute blood volume and an increase in myocardial tolerance to stress in patients with chronic heart failure. Expands arteries more than veins. Some of the effects are attributed to the effect on tissue renin-angiotensin systems.With prolonged use, the hypertrophy of the myocardium and the walls of the resistive arteries decreases. Improves blood supply to the ischemic myocardium.
The duration of the effect also depends on the size of the dose. The onset of action is after 1 hour. The maximum effect is determined after 6-7 hours. The action lasts 24 hours. With arterial hypertension, the effect is observed in the first days after the start of treatment, a stable effect develops after 1–2 months.
In patients with chronic heart failure, Lisinopril, by reducing the total peripheral vascular resistance, reduces the afterload on the heart, increases the stroke and cardiac output without increasing the heart rate, and increases exercise tolerance.In addition, Lisinopril reduces preload, reduces pressure in the pulmonary circulation and in the right atrium, and causes regression of myocardial hypertrophy.
Two large randomized trials ONTARGET and VA NEPHRON-D examined the combination of ACE inhibitors and angiotensin II receptor blockers in patients with cerebrovascular disease and type II diabetes mellitus with target organ damage or diabetic nephropathy. These studies did not reveal significant benefits for patients in terms of preserving renal function, cardiovascular outcomes and mortality, but, at the same time, were accompanied by an increase in the incidence of renal dysfunction, hypotension compared with monotherapy.Given the similar characteristics of all ACE inhibitors, the results of these studies can be extended to the entire group of drugs.
The ALTITUDE study investigated the addition of aliskiren to therapy with an ACE inhibitor or angiotensin II receptor blocker in patients with type II diabetes and kidney or heart disease. The study was terminated early due to the high incidence of adverse outcomes (the risk of cardiovascular mortality or stroke was higher in the aliskiren group).The study also found an increased incidence of adverse effects in the aliskiren group (hyperkalemia, hypotension and renal dysfunction).
Pharmacokinetics
Absorption
After oral administration, lisinopril is absorbed from the gastrointestinal tract. Cmax of lisinopril in plasma is achieved within 6-8 hours. Food intake does not affect the absorption of the drug. Absorption is on average 30%, bioavailability – 29%.
Distribution
Does not bind to plasma proteins.Css of lisinopril with a course of taking the drug is established after 3 days. Permeability through the blood-brain and placental barrier is low.
Metabolism
Lisinopril is not biotransformed in the body.
Withdrawal
It is excreted by the kidneys unchanged. The half-life is 12 hours.
Pharmacokinetics in special clinical cases
In patients with severe renal impairment, an increase in the time to reach Cmax and Css of lisinopril was noted; the dosage regimen for this category of patients must be adjusted taking into account the creatinine clearance rates.

Lisinopril is recommended to be administered orally once a day, at about the same time. Food intake does not affect the absorption of lisinopril tablets. The dose should be determined individually according to the patient’s response and blood pressure.
Arterial hypertension
Lisinopril can be used as monotherapy and in combination with other antihypertensive drugs. See also the sections “Contraindications”, “Special instructions”, “Interaction with other drugs”, “Pharmacodynamics”.
Initial d oz. For patients with arterial hypertension, the recommended starting dose is 10 mg.
Patients with a very active renin-angiotensin-aldosterone system (in particular with renovascular hypertension, increased salt excretion from the body and / or decreased intercellular fluid volume, heart failure or severe arterial hypertension) may experience a significant decrease in blood pressure after taking the initial dose.For such patients, the recommended dose is 2.5–5 mg, and the initiation of treatment should take place under the direct supervision of a physician. A reduction in the starting dose is also recommended for renal impairment (see table below).
Maintenance dose. The usual recommended maintenance dose is 20 mg once daily. If the appointment of this dose does not give a sufficient therapeutic effect within 2-4 weeks, it can be increased. The maximum daily dose is 80 mg.
Treatment of arterial hypertension in children aged 6-16 years
The recommended starting dose is 2.5 mg once daily in patients weighing 20 to
Patients taking diuretics
Symptomatic hypotension may occur after starting treatment with Lisinopril. This is likely for patients taking diuretics while being treated with Lisinopril. Such patients are advised to take the drug with caution because of the likelihood of increased excretion of salt from the body and / or a decrease in the volume of intercellular fluid.If possible, it is necessary to stop diuretic treatment 2-3 days before starting therapy with Lisinopril. For hypertensive patients who cannot discontinue diuretic therapy, therapy should be started with a dose of 5 mg. It is necessary to monitor renal function and serum potassium levels. Subsequent doses of Lisinopril must be selected in accordance with the blood pressure response. If necessary, diuretic therapy can be resumed.
The dosage for patients with renal impairment should be based on QC as shown in the table below.
Table. Dose selection for patients with renal insufficiency.

* – the dosage and / or frequency of administration must be calculated based on the indicators of the blood pressure response.
The dose can be gradually increased until blood pressure is normalized, or until a maximum dose of 40 mg per day is reached.
Chronic heart failure
Patients with symptomatic heart failure should take Lisinopril as adjunctive therapy to diuretics, digitalis drugs, or β-blockers. Lisinopril therapy can be started with a dose of 2.5 mg once a day, the drug must be taken under the supervision of a physician in order to identify the initial effect of the drug on blood pressure.
The dosage of Lisinopril must be increased:
• increasing the dose by no more than 10 mg;
• the intervals between dose increases should be at least 2 weeks;
• up to the highest dose tolerated by the patient, up to a maximum of 35 mg once a day.
Dose selection should be based on the clinical response of each individual patient.
Patients who are at high risk of symptomatic hypotension, for example, patients with an increased level of salt excretion from the body with or without hyponatremia, patients with hypovolemia, or patients who have received intensive diuretic therapy, need to improve their condition, if possible, before starting lisinopril therapy.It is necessary to monitor renal function and serum potassium levels.
Acute myocardial infarction
Depending on the circumstances, the patient should undergo the standard recommended therapy, such as treatment with thrombolytics, aspirin, and β-adrenergic blockers. Along with this, nitroglycerin can be used (including transdermal).
Initial dose (first 3 days after a heart attack).
Treatment with lisinopril can be started in the first 24 hours after the first symptoms appear.Treatment should not be started if systolic blood pressure is less than 100 mm Hg. Art. The initial dose of lisinopril is 5 mg orally, then 5 mg after 24 hours, 10 mg after 48 hours and 10 mg daily. Patients with systolic pressure not exceeding 120 mm Hg. Art., before or during therapy in the first 3 days after a heart attack, treatment should be started with a low dose of 2.5 mg.
In renal failure (creatinine clearance
Maintenance dose .The recommended maintenance dose is 10 mg once a day. In case of arterial hypotension (systolic pressure less than 100 mm Hg), the maintenance daily dose should not exceed 5 mg, if necessary, the specified dose can be reduced to 2.5 mg. If, after taking Lisinopril, prolonged arterial hypotension is observed (systolic pressure remains less than 90 mm Hg for more than 1 hour), therapy with Lisinopril should be discontinued. Treatment is recommended for 6 weeks, then a re-assessment of the patient’s condition is necessary.Patients with symptoms of heart failure need to continue treatment.
Elderly patients
In clinical trials, there were no age-related changes in the efficacy or safety of the drug.
However, reaching a certain age is associated with a decrease in renal function, the initial dose of lisinopril must be selected in accordance with the instructions given in the table. After that, the dose must be selected in accordance with the reaction and blood pressure.

When using Lisinopril, like other ACE inhibitors, a number of side effects may occur with the following frequency: very frequent (1/10), frequent (1/100 <1/10), infrequent (1/1000 <1/100), rare (1/10000 <1/1000), very rare (<1/10000), unknown (cannot be estimated from the available data).
Disorders of the blood and lymphatic system : rare – decreased hemoglobin, decreased hematocrit, very rare – bone marrow suppression, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia, lymphadenopathy, autoimmune diseases.
Nutritional and metabolic disorders : very rare – hypoglycemia.
Disorders of the nervous system and psyche : frequent – dizziness, headache, infrequent – mood swings, paresthesia, dizziness, taste disorder, sleep disorder, rare – confusion, olfactory disorders, frequency is not known – symptoms of depression, loss of consciousness.
Disorders of the heart and blood vessels : frequent – orthostatic effects, including hypotension, infrequent – myocardial infarction or cerebrovascular disorders, secondary hypotension may develop in high-risk patients, palpitations, tachycardia, Raynaud’s syndrome.
Respiratory and chest disorders : frequent – cough, infrequent – rhinitis, very rare – bronchospasm, sinusitis, allergic alveolitis / eosinophilic pneumonia.
Gastrointestinal disorders : frequent – diarrhea, vomiting, infrequent – nausea, abdominal pain, dyspepsia, rare – dry mouth, very rare – pancreatitis, intestinal angiodema, hepatitis – or hepatocellular or cholestatic, jaundice and liver failure.
Disorders of the skin and subcutaneous tissue : infrequent – redness, itching, increased sensitivity / angioedema (angioedema of the face, lips, tongue, pharynx and / or larynx), rare – urticaria, alopecia, psoriasis, very rare – sweating , pemphigus, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, cutaneous pseudolymphoma. There is a report of a symptom complex that includes one or more of the following symptoms: fever, vasculitis, myalgia, arthralgia / arthritis, antinuclear antibodies, increased ESR, eosinophilia and leukocytosis, skin rash, skin photosensitivity and other skin manifestations.
Disorders of the kidneys and urinary tract : frequent – renal dysfunction, rare – uremia, renal failure, very rare – oliguria / anuria.
Endocrine disorders : frequency not known – inadequate secretion of antidiuretic hormone.
Disorders from the reproductive system and mammary glands : infrequent – impotence, rare – gynecomastia.
General disorders and disorders at the injection site : infrequent – fatigue, asthenia.
Laboratory tests : infrequent – increased blood urea, increased serum creatinine, increased activity of liver enzymes, hyperkalemia, rare – increased serum bilirubin, hyponatremia.

Diuretics .With the simultaneous use of the drug with diuretics, a sharp decrease in blood pressure is possible, with other antihypertensive drugs – an additive effect is observed (with combination therapy, caution is required).
Potassium preparations, potassium-sparing diuretics . With simultaneous use with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and dietary supplements containing potassium, hyperkalemia may develop, especially in patients with impaired renal function.When using such combinations, regular monitoring of potassium in the blood and kidney function is required.
Lithium . Reversible increases in serum lithium concentrations and toxicity have been reported during the combined use of lithium with ACE inhibitors. Concomitant use of thiazide diuretics with ACE inhibitors may further increase the risk of lithium toxicity. The simultaneous administration of lisinopril with lithium is not recommended, but if such a combination is necessary, careful monitoring of the lithium content in the blood serum is necessary.
Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid 3 g / day. When ACE inhibitors are used concomitantly with non-steroidal anti-inflammatory drugs (for example, acetylsalicylic acid with an anti-inflammatory dosing regimen, COX-2 inhibitors and non-selective NSAIDs), a weakening of the antihypertensive effect may occur. The simultaneous use of ACE inhibitors and NSAIDs can lead to an increased risk of deterioration of renal function, including the possibility of acute renal failure, as well as an increase in serum potassium concentration, especially in patients with impaired renal function.These effects are usually reversible. Combinations of ACE inhibitors and NSAIDs should be used with caution, especially in the elderly. Patients must maintain adequate water balance; after the course of therapy, it is necessary to check the function of the kidneys.
Gold preparations . Nitrate-like reactions (symptoms of vasodilation, including hot flashes, nausea, dizziness and hypotension, which can be very severe) can often develop with the simultaneous administration of ACE inhibitors and gold preparations in the form of injections.
Other antihypertensive drugs . The simultaneous use of these drugs can increase the hypotensive effect of lisinopril.
Concurrent use with nitroglycerin and other nitrates or other vasodilators may further lower blood pressure.
Tricyclic antidepressants / neuroleptics / anesthetics . The simultaneous use of certain anesthetics, tricyclic antidepressants and antipsychotics with ACE inhibitors can further lower blood pressure.
Sympathomimetics . Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.
Antidiabetic drugs . Epidemiological studies have shown that the simultaneous use of ACE inhibitors and antidiabetic drugs (insulin, oral hypoglycemic agents) can enhance the hypoglycemic effect of the latter with the risk of hypoglycemia. This effect is more likely during the first weeks of combination therapy and in patients with renal impairment.
Acetylsalicylic acid, thrombolytics, beta-blockers, nitrates . Lisinopril can be used simultaneously with acetylsalicylic acid (in dosages providing an antiplatelet effect), thrombolytics, beta-blockers and / or nitrates.
Double blockade of the renin-angiotensin-aldosterone system (RAAS).
Based on the available data, dual blockade of RAAS using an ACE inhibitor, ARB II or aliskiren cannot be recommended for any patient, especially for patients with diabetic nephropathy.
In patients with diabetes mellitus or moderate / severe renal impairment (GFR <60 ml / min / 1.73 m2), the simultaneous use of aliskiren with an ACE inhibitor or ARB II is contraindicated.
In some cases, when the combined use of an ACE inhibitor and ARB II is absolutely indicated, careful observation by a specialist and mandatory monitoring of renal function, water-electrolyte balance, and blood pressure is necessary.

Symptomatic hypotension is more likely to occur in patients with more severe heart failure receiving high doses of loop diuretics, hyponatremia, or impaired renal function.In patients with an increased risk of symptomatic hypotension, the initiation of therapy and dose adjustment should be carefully monitored. Such measures apply to patients with coronary heart disease or cerebrovascular accident, in whom an excessive decrease in blood pressure can lead to myocardial infarction or stroke.
Often, hypotension, especially after the first dose, can develop in patients with severe heart failure, this should be taken into account when prescribing lisinopril.If hypotension occurs, the patient should be laid on his back, if necessary, an infusion of 9 mg / ml of sodium chloride solution should be performed. A short-term hypotensive reaction is not a contraindication for further doses, which can usually be easily administered after the restoration of the effective blood volume and the disappearance of the fleeting hypotensive reaction.
Arterial hypotension in acute myocardial infarction . In acute myocardial infarction, treatment with Lisinopril should not be started if, through the preliminary use of vasodilators, there is a risk of further serious hemodynamic disturbances.This applies to patients with a systolic blood pressure of 100 mm Hg. Art. or less, or cardiogenic shock. During the first 3 days after myocardial infarction, the dose of the drug must be reduced if the systolic pressure does not exceed 120 mm Hg. Art. If the systolic blood pressure is equal to or less than 100 mm Hg. Art., the selected doses must be reduced to 5 mg or temporarily to 2.5 mg. If, after taking Lisinopril, prolonged arterial hypotension is observed (systolic pressure remains less than 90 mm Hg.Art. for more than 1 hour), it is necessary to cancel the treatment with Lisinopril.
Aortic and mitral valve stenosis / hypertrophic cardiomyopathy. As with other ACE inhibitors, Lisinopril should be used with caution in patients with mitral valve stenosis or obstruction of left ventricular ejection, such as aortic stenosis or hypertrophic cardiomyopathy.
Renal dysfunction. In case of renal failure (creatinine clearance <80 ml / min), the initial dose of Lisinopril should be adjusted according to the patient's creatinine clearance (see.table), and then - depending on the patient's response to treatment. Serum potassium and creatinine clearance should be monitored daily in these patients.
In patients with heart failure, hypotension after starting treatment with ACE inhibitors can lead to further deterioration of renal function. In such cases, the development of acute renal failure, usually reversible, has been reported.
In some patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney, who took ACE inhibitors, increased serum urea and creatinine levels usually returned to normal after discontinuation of therapy.More often, levels increased in patients with renal insufficiency. In the presence of renovascular hypertension, the risk of severe arterial hypotension and renal failure increases. Treatment of such patients should be started under medical supervision, low doses and careful selection. Since diuretic therapy can contribute to all of the above, they should be discontinued and renal function monitored during the first weeks of treatment with Lisinopril.
In some patients with arterial hypertension without obvious vascular diseases of the kidneys, taking Lisinopril, especially against the background of diuretics, causes an increase in the level of urea in the blood and creatinine in the blood serum.These changes are usually minor and transient. More often in patients with a history of renal failure. In this case, it may be necessary to reduce the dose of the drug and / or stop taking the diuretic and / or Lisinopril.
Treatment of acute myocardial infarction with Lisinopril is not indicated in patients with signs of renal dysfunction, in which there is an increased level of serum creatinine> 177 μmol / L and / or proteinuria> 500 mg / day. If renal failure develops during treatment with lisinopril (serum creatinine concentration> 265 μmol / l, or a 2-fold increase in the indicator before treatment), then the doctor may consider discontinuing lisinopril.
Hypersensitivity / angioedema . In very rare cases, angioedema of the face, limbs, lips, tongue, glottis and / or larynx has been reported in patients treated with ACE inhibitors. During the treatment period, angioedema can occur at any time. In such cases, the drug should be stopped immediately, appropriate therapy should be started and observation should be established to ensure the complete disappearance of symptoms. In cases where the edema is localized in the region of the tongue, which does not lead to respiratory failure, the patient may require long-term observation, since therapy with antihistamines and GCS may be insufficient.
Anaphylactic reactions in patients undergoing hemodialysis. Anaphylactic reactions have been reported in patients undergoing hemodialysis using high-flow membranes (eg, AN 69) and concomitantly treated with ACE inhibitors. These patients should be offered to change the dialysis membrane to a different type of membrane or to use a different class of antihypertensive drug.
Desensitization. Persistent anaphylactoid reactions develop in patients taking ACE inhibitors during desensitizing therapy (for example, hymenoptera venom).These reactions were avoided in these patients by temporarily stopping the ACE inhibitors, but after careless repeated use of the drug, the reactions were restored.
Liver failure. Very rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses rapidly to necrosis and (sometimes) death. The mechanism of this syndrome has not been identified. Patients who develop jaundice or a significant increase in liver enzymes while taking lisinopril should stop taking the drug and provide appropriate medical care.
Neutropenia / agranulocytosis. Cases of neutropenia / agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia is rare. After discontinuation of an ACE inhibitor, neutropenia and agranulocytosis are reversible. It is necessary to take lisinopril with extreme caution in patients with vascular collagenosis, as well as when patients receive immunosuppressive therapy, when treated with allopurinol or procainamide, or a combination of these complicating factors, especially against the background of impaired renal function.When using the drug, such patients are advised to periodically monitor the number of leukocytes in the blood and warn the patient about the need to report any signs of infection.
Cough. After using ACE inhibitors, coughing may occur. Usually, the cough is unproductive and stops after discontinuation of therapy. Cough caused by ACE inhibitors should be considered in the differential diagnosis of cough as one of the options.
Surgical procedures / anesthesia. In patients undergoing general surgery or anesthesia with hypotensive drugs, lisinopril may block the formation of angiotensin II after compensatory renin secretion. If arterial hypotension is observed due to this mechanism, it is necessary to correct the level of BCC.
Hyperkalemia. Several cases of increased serum potassium levels have been reported in patients treated with ACE inhibitors, including lisinopril.Patients at high risk of developing hyperkalemia include those with renal failure, diabetes mellitus, or who are taking potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes at the same time, or who are taking other drugs that increase serum potassium levels (for example, heparin). If the concomitant use of these drugs is considered appropriate, regular monitoring of serum potassium levels is recommended.
Patients with diabetes mellitus. In diabetic patients taking oral antidiabetic drugs or insulin, close glycemic control should be exercised during the first month of therapy with ACE inhibitors.
Anaphylactoid reactions occurring during apheresis of low density lipoprotein (LDL). Since with apheresis of LDL with dextran sulfate, the use of ACE inhibitors can lead to anaphylactic reactions that can be life-threatening, you should temporarily discontinue ACE inhibitors before each use.
Racial . ACE inhibitors can cause more severe angioedema in darker skinned patients than in Caucasian patients. Also, in this group of patients, the hypotensive effect of lisinopril is less pronounced due to the predominance of low fractions of renin.
Lithium . The combination of lithium and lisinopril is not recommended.
Double blockade of the renin-angiotensin-aldosterone system (RAAS) . Double blockade of the RAAS is associated with an increased risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure) compared with monotherapy.Double blockade of RAAS with the use of an ACE inhibitor, ARB II, or aliskiren cannot be recommended for any patient, especially for patients with diabetic nephropathy.
In some cases, when the combined use of an ACE inhibitor and ARB II is absolutely indicated, careful observation by a specialist and mandatory monitoring of renal function, water-electrolyte balance, and blood pressure is necessary. This also applies to the appointment of candesartan or valsartan as adjunctive therapy to ACE inhibitors in patients with heart failure.Conducting a double blockade of the RAAS under the close supervision of a specialist and mandatory monitoring of renal function, water-electrolyte balance and blood pressure, is possible in patients with chronic heart failure with intolerance to aldosterone antagonists (spironolactone), who have persistent symptoms of chronic heart failure, despite other adequate therapy.

Symptoms : arterial hypotension, circulatory shock, bradycardia, water and electrolyte disturbances, renal failure, hyperventilation, tachycardia, increased heart rate, dizziness, anxiety and cough.
Treatment : Intravenous saline. In cases of arterial hypotension, the patient must be placed in a horizontal position. If possible, you can apply the introduction of angiotensin II and I or the introduction of catecholamines. If the drug has been used recently, take measures to remove lisinopril from the body (for example, induce vomiting, gastric lavage, use of absorbents and sodium sulfate). The use of a pacemaker is indicated in patients with resistance to bradycardia therapy.It is necessary to frequently check vital organs, the concentration of electrolytes and serum creatinine.
Lisinopril can be removed from the body by hemodialysis, while the use of high-throughput membranes of polyacrylonitrile sodium-2-methylsulfonate (eg AN 69) should be avoided.

Lisinopril-Teva, 10 mg, tablets, 30 pcs.

Cardiovascular system: sometimes, especially at the beginning of therapy or with an increase in the dose of lisinopril and / or diuretics, an excessive decrease in blood pressure is possible. This is most likely in patients with salt or fluid deficiency following diuretic treatment, in patients with heart failure and severe or renovascular hypertension. Symptoms include dizziness, general weakness, blurred vision, and (sometimes) loss of consciousness (fainting).

There are isolated reports of the following side effects of ACE inhibitors associated with a strong drop in blood pressure: tachycardia, palpitations, arrhythmias, chest pain, angina pectoris, myocardial infarction, transient decrease in cerebral circulation, stroke.

When lisinopril is prescribed to patients with acute myocardial infarction, especially in the first 24 hours, AV block of 2 or 3 degrees and / or severe arterial hypotension and / or renal failure, in rare cases – and cardiogenic shock may develop.

During therapy with ACE inhibitors, isolated cases of increased vasospasm in Raynaud’s syndrome were noted.

Kidney: development or worsening of symptoms of renal failure, in some cases up to acute renal failure.Rare cases of proteinuria have been reported, sometimes in combination with impaired renal function.

Respiratory system: dry cough, sore throat, hoarseness and bronchitis; difficulty breathing, sinusitis, rhinitis, bronchospasm / asthma, pulmonary infiltration, stomatitis, glossitis, and dry mouth are rare. The cough is usually persistent, without mucus, and disappears after stopping the drug. In isolated cases, angioedema of the larynx, throat and / or tongue led to a narrowing of the airways with a fatal outcome.There are isolated reports of cases of alveolitis (chronic eosinophilic pneumonia).

GI tract / liver: nausea, stomach pain, rarely – vomiting, diarrhea, constipation, loss of appetite.

During therapy with ACE inhibitors, a syndrome was occasionally observed that begins with cholestatic jaundice, turning into liver necrosis, in which a fatal outcome is possible. The mechanism of this syndrome is unknown. If jaundice occurs during therapy with ACE inhibitors, it is necessary to discontinue the drug and medical monitoring of the patient’s condition.

During therapy with ACE inhibitors, there have been isolated cases of liver dysfunction, hepatitis, liver failure, pancreatitis and intestinal obstruction.

Skin, blood vessels: allergic skin reactions (rash, rarely urticaria, itching, and angioedema of the face, lips and / or extremities). There are sporadic reports of severe skin reactions, including pemphigus, erythema polymorphism, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Lyell’s syndrome).

Skin reactions may be accompanied by fever, myalgia, arthralgia, vasculitis and changes in a number of laboratory parameters (eosinophilia, leukocytosis and / or a positive test for antinuclear antibodies).

If a severe skin reaction is suspected, urgent consultation with a specialist and discontinuation of lisinopril is necessary.

During therapy with ACE inhibitors, isolated cases of psoriasis-like skin reactions, photosensitivity reactions, flushing of the face, excessive sweating, hair loss, and nail detachment (onycholysis) were noted.

CNS: headache and increased fatigue, less often – drowsiness, depression, sleep disturbance, impotence, tingling sensation, peripheral neuropathy (including paresthesias, imbalance and muscle cramps), increased nervousness, confusion, tinnitus, blurred vision and violation (dysgeusia) or temporary loss (ageusia) of taste sensitivity.

Laboratory test data (urine, blood): decrease in hemoglobin level, hematocrit, leukocyte or platelet count.In rare cases (mainly in patients with reduced renal function, connective tissue diseases or receiving allopurinol, procainamide or some immunosuppressants) – anemia, thrombocytopenia, neutropenia, eosinophilia, in rare cases – agranulocytosis or pancytopenia.

There are isolated reports of hemolytic anemia in patients with congenital glucose deficiency; 6-phosphate dehydrogenase.

In rare cases, mainly in patients with renal dysfunction, severe heart failure and renovascular hypertension, it is possible to increase the level of urea, creatinine and potassium ions and a decrease in the level of sodium ions in the blood serum.In patients with diabetes mellitus, hyperkalemia is possible.

Lisinopril-Teva 20 mg No. 30 tab.

Instructions for medical use

medicinal product

Lisinopril-Teva

Trade name

Lisinopril-Teva

International non-proprietary name

Lisinopril

Dosage form

Tablets 5 mg, 10 mg, 20

One tablet contains

active substance – lisinopril dihydrate 5.44 mg, 10.89 mg or 21.78 mg, equivalent to anhydrous lisinopril 5 mg, 10 mg, 20 mg,

excipients: mannitol, calcium hydrogen phosphate dihydrate, pregelatinized starch, PB-24823 dye, croscarmellose sodium, magnesium stearate.

Description

Tablets, white, round, biconvex, with a score on one side (for a dosage of 5 mg).

Tablets light pink, round, biconvex, with a score on one side (for a dosage of 10 mg).

Tablets pink, round, biconvex with a score on one side (for a dosage of 20 mg).

Pharmacotherapeutic group

Drugs affecting the renin-angiotensin system. Angiotensin converting enzyme (ACF) inhibitors.Lisinopril.

ATC code C09AA03

Pharmacological properties

Pharmacokinetics

The maximum plasma concentration is reached approximately 7 hours after oral administration. Food intake does not affect the rate of absorption of lisinopril. Lisinopril does not bind to blood plasma proteins. The absorbed biologically active substance is completely and unchanged excreted through the kidneys. The effective half-life was 12.6 hours. Lisinopril crosses the placenta.

Pharmacodynamics

Lisinopril-Teva is an angiotensin converting enzyme (ACE inhibitor) inhibitor. The suppression of ACE leads to a reduced formation of angiotensin II (with a vasoconstrictor effect) and to a decrease in the secretion of aldosterone. Lisinopril-Teva also blocks the breakdown of bradykinin, a powerful vasodepressor peptide. As a result, it lowers blood pressure, total peripheral vascular resistance, pre- and afterload on the heart, increases minute volume, cardiac output and increases myocardial tolerance to stress and improves blood supply to the ischemic myocardium.In patients with acute myocardial infarction, Lisinopril-Teva, together with nitrates, reduces the formation of left ventricular dysfunction or heart failure.

Indications

– arterial hypertension

– chronic heart failure (as part of complex therapy with diuretics and cardiac glycosides)

– acute myocardial infarction in patients with stable hemodynamics without signs of renal dysfunction.

Route of administration and dosage

Arterial hypertension:

Treatment should begin with 5 mg daily in the morning.The dose should be adjusted in such a way as to provide optimal control of the blood pressure level. The time interval between dose increases should be at least 3 weeks. The usual maintenance dose is 10–20 mg of lisinopril once a day, with a maximum daily dose of 40 mg once a day.

Heart failure:

Lisinopril-Teva is prescribed in addition to the existing therapy with diuretics and digitalis. The starting dose is 2.5 mg in the morning. The maintenance dose should be set in increments of 2.5 mg at intervals of 2-4 weeks.The usual maintenance dose is 5–20 mg once a day. Do not exceed the maximum dose of 35 mg lisinopril / day.

Acute myocardial infarction in patients with stable hemodynamics:

Treatment with Lisinopril-Teva can begin within 24 hours after the onset of symptoms, provided that the hemodynamics are stable (systolic pressure is more than 100 mm Hg, without signs of renal dysfunction), in addition to the standard heart attack therapy (thrombolytic agents, acetylsalicylic acid, beta-blockers, nitrates).The initial dose is 5 mg, after 24 hours – another 5 mg, after 48 hours – 10 mg. Then the dose is 10 mg of lisinopril 1 time per day.

Patients with low systolic pressure (≤ 120 mm Hg) before starting therapy or during the first 3 days after a heart attack should receive a lower therapeutic dose for treatment – 2.5 mg of Lisinopril-Teva. If the systolic pressure is less than 90 mm Hg. Art. more than 1 hour, you should abandon Lisinopril-Teva.

Treatment should continue for 6 weeks.The minimum maintenance dose is 5 mg per day. Patients with symptoms of heart failure should continue to be treated with Lisinopril-Teva. The drug can be given simultaneously with nitroglycerin (intravenously or as a skin patch).

In myocardial infarction, lisinopril should be given in addition to the usual standard therapy (thrombolytic agents, acetylsalicylic acid, beta-blockers), preferably together with nitrates.

Elderly patients:

In elderly patients, the dosage should be adjusted taking into account the creatinine level (to assess renal function), which is calculated using the Cockcroft formula:

Creatinine clearance =

(140 – age) × body weight (kg)

0.814 × serum creatinine concentration (μmol / L)

(For women, the result obtained using this formula must be multiplied by 0.85).

Dosage in patients with moderately limited renal function (creatinine clearance 30 – 70 ml / min):

The initial dose is 2.5 mg of the drug in the morning, the maintenance dose is 5-10 mg per day. Do not exceed the maximum dose of 20 mg of lisinopril per day.

Lisinopril-Teva can be taken regardless of meals, but with sufficient liquid, once a day, preferably at the same time.

Side effects

Sometimes

– headaches, dizziness, feeling of weakness, visual disturbances, fatigue

– dry cough, sore throat

– nausea, loss of appetite, diarrhea, constipation, vomiting

– allergic rash

Rarely

– stunned consciousness, depression, sleep disturbances, tinnitus, disturbances in the sense of balance, nervousness, changes in taste

– peripheral neuropathy with paresthesia, muscle cramps, hot flashes, sweating

– shortness of breath, bronchospasm, allergic alveolitis

– tachycardia, cardiac arrhythmias, cardiogenic shock, chest pain, orthostatic hypotension

– cholestatic jaundice, proteinuria and increased serum bilirubin and liver enzymes

– anemia, thrombocytopenia, neutropenia, eosinophilia, in some cases, pancytopenia; an increase in the concentration of urea, creatinine and potassium and a decrease in the concentration of sodium in the blood serum (in patients with impaired renal function)

– in some cases: hemolytic anemia in patients with a significant deficiency of glucose-3-phosphate dehydrogenase

– itching, urticaria , angioedema, pemphigus, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrosis, psoriasis, photosensitivity, alopecia, onycholysis

– Raynaud’s syndrome

– impotence

Very rare

– Very rare

– – increased susceptibility to the active substance or other ACE inhibitors or one of the excipients

– renal artery stenosis (bilateral or unilateral with one kidney)

– a history of angioedema due to previous therapy with an ACE inhibitor and hereditary / spontaneous angioedema

Immediate use of lisinopril with products containing aliskiren in patients with diabetes mellitus or renal failure (GFR <60 ml / min / 1.73 m2)

– severe renal dysfunction (creatinine clearance <30 ml / min).

– hemodynamically relevant stenosis of the aorta or mitral valve or hypertrophic cardiomyopathy

– acute myocardial infarction in patients with unstable hemodynamics

– systolic pressure ≤ 100 mm Hg. Art. before treatment

– breastfeeding

– pregnancy and lactation

– cardiogenic shock

– children under 18 years old

– primary hyperaldosteronism

– condition after kidney transplantation

Drug interactions

With simultaneous use of tablets Lisinopril-Teva and:

– lithium excretion of lithium from the body may be reduced, therefore it is necessary to carefully monitor the concentration of lithium in the blood serum

– analgesics, non-steroidal anti-inflammatory drugs (for example, acetylsalicylic acid, indomethacin) – the hypotensive effect of lisinopril may be weakened

– baclofen – it is possible to increase the hypotensive effect of lisinopril; diuretics – it is possible to increase the hypotensive effect of lisinopril

– potassium-sparing diuretics (spironolactone, triamterene or amiloride) and potassium supplements the risk of hyperkalemia increases 9 0015

– antihypertensive drugs – an increase in the hypotensive effect of lisinopril is possible

– anesthetics, drugs, hypnotics – a sharp decrease in blood pressure is possible

– allopurinol, cytostatics, immunosuppressants, systemic corticosteroids, procainamide – the risk of developing leukopenia

(sulfonylurea derivatives, biguanides) and insulin – an increase in the hypotensive effect is possible, especially in the first weeks of combination therapy.

– amifostine – an increase in the hypotensive effect is possible

– antacids – a decrease in the bioavailability of lisinopril

– sympathomimetics – an increase in the hypotensive effect is possible

– alcohol – an increase in the effect of alcohol is possible

– table salt – a weakening of the hypotensive effect of symptoms of lisinopril and failure.

Specific guidance

Patients receiving multiple or high-dose diuretics (> 80 mg furosemide / day), patients with hypovolemia, hyponatremia (serum sodium <130 mmol / L), pre-existing hypotension, unstable heart failure , limited renal function, high-dose therapy with vasodilators and patients aged 70 years and older, it is recommended to start therapy with Lisinopril-Teva inpatiently.

Concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, a double blockade of the renin-angiotensin-aldosterone system due to the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended.

If dual block therapy is absolutely necessary, this should only be done under the supervision of a specialist and with close monitoring of renal function, electrolytes and blood pressure.ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

With the development of hypotension, strict medical supervision is necessary, taking diuretics in low doses and carefully grinding the dose of the drug into powder while monitoring kidney function and potassium levels. If possible, diuretic therapy should be temporarily discontinued 2-3 days before starting lisinopril therapy. This should also be taken into account in patients with angina pectoris or other cardiovascular diseases in whom myocardial infarction or stroke may develop due to an excessive drop in blood pressure.

When hypotension develops, the patient should be placed on his back; if necessary, the volume of lost fluid is replaced. With bradycardia, atropine is prescribed.

Hemodialysis / LDL-lipid-apheresis / Therapy for desensitization

With the simultaneous use of lisinopril and dialysis with a polyacryl-nitrile membrane or LDL (low density lipoprotein) -apheresis with dextran sulfate or desensitization against bees, insects), it is possible ( development of anaphylactic shock.

It is recommended to use a different dialysis membrane or temporarily replace Lisinopril-Teva with other antihypertensive drugs (not ACE inhibitors).

Angioedema

With the development of angioedema of the face and lips, antihistamines are prescribed. Swelling of the tongue, glottis and / or larynx can be life threatening, therefore emergency treatment is performed, with immediate subcutaneous injection of 0.3-0.5 mg epinephrine or slow intravenous injection of 0.1 mg epinephrine (follow dilution instructions), with ECG monitoring and blood pressure.

Features of the influence of the drug on the ability to drive a vehicle or potentially dangerous machinery

It is necessary to control the level of blood pressure, because due to individual characteristics, some patients may develop hypotension and, as a result, impair the ability to drive vehicles and service moving mechanisms.

Overdose

Symptoms: severe hypotension, shock, bradycardia.

Treatment: The patient must be under strict medical supervision, preferably in an intensive care unit.Serum electrolyte and creatinine concentrations should be monitored frequently. Measures that prevent absorption, such as gastric lavage, the appointment of adsorbents and sodium sulfate, should be taken within 30 minutes after taking the drug. Lisinopril is removed by hemodialysis.

Release form and packaging

10 tablets in a blister strip made of PVC film and aluminum foil. 3 or 5 contour packs, together with instructions for use in the state and Russian languages, are placed in a cardboard box.

Storage conditions

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life

4 years

Do not use after the expiration date.

Terms of dispensing from pharmacies

Prescription

Manufacturer

Merkle GmbH, Germany

Registration certificate holder

Ratiopharm GmbH, Germany

Address of the organization that receives claims from consumers on the quality of products in the Republic of Kazakhstan (goods)

LLP “ratiopharm Kazakhstan”, 050040, g.Almaty, 19 Al-Farabi ave., BC Nurly-Tau, 1B, office 603.

Address of the organization, in the territory of the Republic of Kazakhstan, responsible for post-registration monitoring of drug safety

Ratiopharm Kazakhstan LLP, 050040, Almaty , Al-Farabi ave. 19, BC Nurly Tau, 1B, office 603.

Use of lisinopril in arterial hypertension :: DIFFICULT PATIENT

Lisinopril is one of the most well-known and well-studied ACE inhibitors, considered a prototype drug.Like other drugs in this group, the main mechanism of action is based on blocking the active zinc-containing domain of the angiotensin-converting enzyme, which causes a decrease in the synthesis of angiotensin II and a decrease in the activity of the renin-angiotensin system as a whole. This effect determines the main indications for the appointment of an ACE inhibitor. These drugs are used in those conditions in the pathogenesis of which RAAS activation may play a role. The main indications, therefore, can be arterial hypertension and heart failure.In addition, the angiotensin converting enzyme is involved in the inactivation of bradykinin. Thus, the other side of the action of ACE inhibitors is the accumulation of tissue bradykinin. This is associated with the development of the main side effects of ACE inhibitors – dry cough, angioedema.
This review summarizes the main data regarding the use of lisinopril in arterial hypertension.
Pharmacokinetic properties of lisinopril
In the chemical structure of lisinopril there is a carboxyl group, which binds the zinc-containing ACE domain.Unlike most ACE inhibitors, lisinopril is not a prodrug. Absorbed in the gastrointestinal tract, it does not undergo further metabolic transformations and is excreted unchanged by the kidneys. The drug has a fairly variable bioavailability – from 6 to 60%. Lisinopril is not lipophilic and practically does not bind to plasma proteins. Its action begins one hour after ingestion, the peak of the effect develops in 4-6 hours, and the duration of action reaches 24 hours, which provides a convenient prescription regimen – once a day.
With the help of daily monitoring of blood pressure, a comparison was made between three regimens of lisinopril administration. The drug was administered as a single dose of 20 mg per day. In this case, the first group of patients took the drug at 8 am, the second at 4 pm and the third at 10 pm. The degree of BP reduction and the duration of the antihypertensive effect was the same in all three treatment groups. When the drug was prescribed at 10 pm, the morning rise in blood pressure associated with the maximum risk of cardiovascular complications was most prevented.Apparently, such a regimen for prescribing the drug should be preferable [1].
Lisinopril in the treatment of arterial hypertension
For the treatment of arterial hypertension lisinopril has been used for a long time, and nowadays a lot of data have been accumulated confirming the good efficacy of lisinopril in comparison with other ACE inhibitors and antihypertensive drugs of other groups.
A direct comparison of the effectiveness of two ACE inhibitors – enalapril and lisinopril – was carried out using blood pressure monitoring to control the effectiveness of therapy.The target BP was 140/90 mm Hg. Art., and the dose of both drugs was titrated to achieve this level of blood pressure. Hydrochlorothiazide was added as needed. Both drugs significantly reduced blood pressure, but the effect of lisinopril was more pronounced. The average doses of drugs at the end of the study were in one group 18 mg of enalapril and 8 mg of hypothiazide, in the second group – 17 mg of lisinopril and 6 mg of a diuretic. It turned out that with the same administration regimen (once a day), lisinopril has a longer duration of action.Drug tolerance did not differ [2].
In another study, when directly comparing the efficacy of enalapril and lisinopril in 367 patients with mild to moderate arterial hypertension, it turned out that lisinopril at a dose of 10-40 mg per day was more effective than enalapril at a dose of 5-20 mg per day [3].
A direct comparison of the effectiveness of lisinopril and quinapril was carried out. The study included 50 patients with mild to moderate arterial hypertension. ACE inhibitor therapy lasted two months.Monitoring the effectiveness of antihypertensive therapy was carried out by monitoring blood pressure. It turned out that lisinopril better reduces both systolic and diastolic blood pressure. Both drugs did not cause significant changes in the blood lipid spectrum and glycemic level [4].
A comparatively small study (65 patients with DBP 95-115 mm Hg) compared the efficacy and tolerability of lisinopril and the b-blocker nebivolol. Lisinopril was prescribed at a dose of 20 mg once a day, nebivolol – 5 mg once a day.Both drugs caused a significant decrease in blood pressure and were well tolerated by patients [5].
Lisinopril is not inferior in efficiency and calcium antagonists. A Danish cooperative study compared the efficacy and tolerability of lisinopril and felodipine in patients with grade 1 and 2 hypertension. A total of 219 patients were included in the study, who were randomized to receive felodipine at a dose of 5-10 mg or lisinopril at a dose of 10-20 mg per day. In general, lisinopril at this dosage was found to be more effective than felodipine.In a subgroup of elderly patients, both drugs were equally effective. Lisinopril was slightly better tolerated by patients. The main side effects were dizziness, weakness, and dry cough. For felodipine, the most common side effects were peripheral edema [6].
Lisinopril surpassed nifedipine in terms of effectiveness in the treatment of arterial hypertension of 1 and 2 degrees. In a Norwegian multicenter study, the hypotensive efficacy, tolerability and impact of these two drugs on quality of life were studied in 828 patients with mild to moderate arterial hypertension.The average dose of lisinopril at the end of the study was 18.8 mg, nifedipine – 37.4 mg per day. Lisinopril was more effective in reducing systolic and diastolic pressure, was better tolerated by patients, and the frequency of side effects was less. Both drugs had the same effect on the quality of life of patients [7].
In women with metabolic syndrome, the efficacy of lisinopril and the imidazoline receptor agonist rilmenidine was compared. Lisinopril was prescribed at a dose of 10 mg, rilmenidine at a dose of 1 mg per day.At the same time, both drugs reduced blood pressure equally. Treatment with both drugs showed a tendency towards normalization of blood lipids and a decrease in blood glucose [8].
The TROPHY study using 24-hour blood pressure monitoring compared the hypotensive efficacy of lisinopril and the diuretic hypothiazide. The study included 124 patients with arterial hypertension and obesity. Lisinopril was prescribed in doses of 10-40 mg, hypothiazide – 12.5-50 mg per day. The duration of treatment was 12 weeks.Both drugs significantly reduced blood pressure, the degree of decrease in systolic blood pressure was the same, and diastolic blood pressure decreased to a greater extent in the lisinopril group. In men, lisinopril, as a rule, was more effective than hypothiazide, in women, the drugs were equally effective. In patients of the black race, a diuretic was more effective, in whites – an ACE inhibitor. When dividing patients into groups according to the type of circadian rhythm of blood pressure, it turned out that non-dippers respond equally to therapy with both drugs, and in dippers lisinopril is more effective [9].
A small study compared the efficacy of lisinopril and an angiotensin receptor blocker (BAR): 32 previously untreated hypertensive patients were randomized to cross-treatment with 80 mg telmisartan or 20 mg lisinopril per day. The efficacy of the ACE inhibitor and BAR turned out to be the same both according to the data of routine office measurements of blood pressure, and according to the data of daily monitoring of blood pressure [10].
In another study on 122 patients with grade 1 arterial hypertension, the same hypotensive efficacy of lisinopril, losartan BAR and amlodipine was shown.As expected, amlodipine caused peripheral edema more often than other drugs, and lisinopril caused dry cough [11].
The efficacy of fixed combinations of candesartan and lisinopril with hydrochlorothiazide was compared in patients with severe arterial hypertension. The study included patients with a DBP level of 95-115 mm Hg. Art. persisted despite previous antihypertensive therapy. The duration of treatment was 26 weeks. The combination of 8 mg candesartan and 12.5 mg of hydrochlorothiazide per day was received by 237 patients, 10 mg of lisinopril and 12.5 mg of hydrochlorothiazide – 116 patients.It turned out that both combinations are equally effective in relation to diastolic blood pressure. As expected, the use of lisinopril showed a slightly higher incidence of side effects (dry cough) [12].
Lisinopril has shown comparable efficacy to the angiotensin receptor blocker valsartan. The large randomized study VAIL (Еhe Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril study) included 1213 patients with grade 1-3 arterial hypertension (SBP 160-220 mm Hg).Art. and DBP 95-110 mm Hg. Art.). Patients were randomized to receive valsartan 160 mg or lisinopril 20 mg per day. After four weeks, hypothiazide was added to therapy with insufficient efficacy. The total duration of treatment was 16 weeks. 1100 patients completed the course of treatment; 51 patients from the valsartan group and 62 patients from the lisinopril group discontinued treatment due to side effects of therapy. The decrease in blood pressure was identical in both treatment groups – 31.2 / 15.9 mm Hg.Art. and 31.4 / 15.9 mm Hg. Art. respectively. As expected, in the lisinopril group, the incidence of such side effects as dry cough was higher (7.2% versus 1.0%) [13].
Lisinopril is one of the drugs that can be recommended for the treatment of hypertension in children and adolescents. In children from 6 to 16 years old, lisinopril, administered in doses of 0.07 mg / kg, was well tolerated and, when administered once a day, effectively reduced blood pressure [14].
Influence on the state of target organs
One of the important requirements for modern antihypertensive drugs is their protective effect against the defeat of the main target organs in hypertension.Target organs include, first of all, left ventricular myocardial hypertrophy, nephropathy. In addition, the effect of antihypertensive therapy on the elasticity of the arteries, the function of the vascular endothelium, which are directly related to the activity of atherosclerotic vascular lesions and the risk of developing cardiovascular complications, is important. There is ample evidence of the good efficacy of lisinopril against target organ damage.
In a relatively small study, 40 patients with arterial hypertension and left ventricular hypertrophy were randomized to be treated with a combination of lisinopril 20 mg with nifedipine SR 30 mg per day or lisinopril at the same dose with hypothiazide 25 mg per day.Both combinations were equally effective in lowering blood pressure. In patients receiving a combination of lisinopril and nifedipine, there was a significantly greater regression of the degree of left ventricular hypertrophy than in patients receiving a combination with a diuretic [15].
Another small study compared the effect of sustained-release lisinopril and nifedipine therapy on left ventricular hypertrophy and the condition of the carotid arteries in hypertensive patients. The blood pressure response was the same in both groups, but the effect on target organs was different.Nifedipine had a greater effect on the thickness of the intima-media (IMT) of the carotid arteries, and lisinopril therapy was more effective in regressing left ventricular myocardial hypertrophy and preventing the development of nephropathy [16].
In the SAMPLE study (Study on Ambulatory Monitoring of blood ssure and Lisinopril Evaluation), the effect of lisinopril on the parameters of blood pressure monitoring and left ventricular myocardial hypertophy in patients with arterial hypertension was studied. Patients received lisinopril therapy at a dose of 20 mg per day for a year, if necessary, in combination with hypothiazide at a dose of 12.5 or 25 mg per day.Lisinopril not only reliably reduced blood pressure both according to office measurements and according to daily blood pressure monitoring data, but also caused a reverse development of left ventricular myocardial hypertrophy [17].
The ELVERA study (Effects of amlodipine and lisinopril on Left Ventricular mass) studied the effect of lisinopril and amlodipine on myocardial mass and left ventricular diastolic function in elderly patients with arterial hypertension who did not receive antihypertensive therapy. The study included 166 patients with arterial hypertension (DBP 95-115 mm Hg).Art. and GARDEN 160-220 mm Hg. Art.) at the age of 60 to 75 years: 81 patients received amlodipine at a dose of 2-10 mg per day, 85 patients received lisinopril at a dose of 10-20 mg per day. The observation period was two years. It turned out that both drugs equally affect the severity of left ventricular myocardial hypertrophy – myocardial mass index decreased by 25.7 g / m2 in the amlodipine group and by 27 g / m2 in the lisinopril group. There were no differences in the effect on left ventricular diastolic function [18]. The effect of these two drugs on the IMT of the carotid and femoral arteries was also studied.Both drugs caused a significant decrease in the IMT of the carotid arteries, which was most pronounced by the end of the first year of observation. At the end of the second year of follow-up, a slight increase in IMT was noted, although the blood pressure level remained at the same level. There were no significant differences in the effect of these two drugs on TIM [19].
In another study of a similar design, 69 hypertensive patients who had not previously received antihypertensive treatment received amlodipine at a dose of 5-10 mg or lisinopril at a dose of 5-20 mg per day.The therapy was continued for 12 months. At the same time, the blood pressure response according to the data of conventional measurements and according to the monitoring data was the same, the mass of the left ventricular myocardium did not differ. In both groups, the same regression of the IMT of the carotid arteries was observed, while the lumen of the common carotid arteries at the end of treatment was significantly larger in the lisinopril group, which, apparently, may be associated with structural changes in the wall of the carotid arteries during treatment with ACE inhibitors [20].
In smokers, treatment with lisinopril at a dose of 20 mg per day for 8 weeks led to an improvement in endothelium-dependent vasodilation.In this case, the vasomotor function of the endothelium was assessed using infusion of acetylcholine, endothelium-independent vasodilation – infusion of nitroglycerin. The reaction of the vessels to the introduction of nitrates after treatment with lisinopril did not change. In this case, the change in vascular reactivity is probably associated not only with the blockade of the renin-angiotensin system, but also with the accumulation of bradykinin [21].
The effect of lisinopril on the state of endothelial regulation of vascular tone was studied in patients with dyslipidemia.Lisinopril was administered to 20 patients at a dose of 20 mg per day, the comparison group received placebo. The duration of treatment was 6 months. As expected, BP was significantly reduced in the lisinopril group. Vasodilation in response to the infusion of acetylcholine and nitroprusside significantly increased at the end of the course of treatment with an ACE inhibitor. In the placebo group, vascular reactivity did not change [22].
Nephropathy is one of the target organ lesions characteristic of arterial hypertension. Different classes of antihypertensive drugs affect the progression of nephropathy in different ways.In a study on 32 patients with arterial hypertension and hypertensive nephropathy, it was shown that only lisinopril therapy improves renal function – reduces the level of albumin excretion, reduces renal vascular resistance. Therapy with nifedipine in combination with hypothiazide, with similar blood pressure control, did not affect renal function in patients with hypertensive nephropathy [23].
Diabetes mellitus and diabetic nephropathy
In patients with diabetes mellitus (DM), ACE inhibitors help not only to slow down the progression of target organ damage and, above all, nephropathy, but also helps to increase tissue sensitivity to insulin.For lisinopril, evidence of efficacy was obtained in this group of patients.
In the multicenter study EUCLID (Randomized placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria), the effect of lisinopril on the progression of diabetic nephropathy and retinopathy in patients with type 2 diabetes mellitus (DM2) without arterial hypertension was studied. In total, the study included 530 patients with diabetes, randomized to treatment with lisinopril or placebo.The level of diastolic blood pressure at inclusion in the study should not have been less than 70 mm Hg. Art and more than 90 mm Hg. Art., systolic blood pressure – not higher than 155 mm Hg. Art. The therapy lasted for two years. At the end of the study, the level of microalbuminuria in the lisinopril group was found to be 18.8% lower than in the placebo group. The maximum effect was in patients who already had nephropathy at the beginning of the study. Patients who received lisinopril had significantly lower levels of glycosylated hemoglobin (6.9% versus 7.3%).The progression of retinopathy was observed in 13.2% of patients in the lisinopril group and in 24.3% of patients in the placebo group [24].
In 21 patients with type 1 diabetes and the initial stage of nephropathy (albumin excretion 20-70 μg / min), the effect of lisinopril therapy on the level of albumin excretion and blood pressure response during exercise was studied. Therapy with lisinopril at a dose of 20 mg per day was carried out for two years. A comparison group matched for age, severity of diabetes, level of glycosylated hemoglobin received placebo.In patients receiving lisinopril, after two years both the excretion of microalbumin and the response of blood pressure to exercise decreased, in the placebo group it increased [25].
In a randomized crossover study on 24 patients with hypertension, the effect of lisinopril and losaratan on insulin sensitivity was studied. Lisinopril was prescribed at a dose of 20 mg, losartan – 50 mg per day. Insulin sensitivity was studied using the CLAMP test. The duration of therapy with each of the drugs was 6 weeks. It turned out that only lisinopril therapy improved insulin sensitivity, although the degree of BP reduction with treatment with both drugs was the same [26].
It has been shown that lisinopril therapy can help to reduce the edema of the optic nerve papilla in patients with diabetes mellitus and arterial hypertension. A decrease in retinal thickness was noted after two months of lisinopril therapy at a dose of 10 mg per day. Efficacy was assessed by measuring retinal thickness and retinal fluorescence angiography [27].
Comparison of the effectiveness of lisinopril and nifedipine retard was carried out in patients with type 2 diabetes, the initial stage of diabetic nephropathy and arterial hypertension (DBP 90-100 mm Hg.Art.). Nifedipine was prescribed at a dose of 20-40 mg twice a day, lisinopril – at a dose of 10-20 mg once a day. A total of 239 men and 96 women were examined. After 12 months of treatment in the lisinopril group, there was a more significant decrease in the rate of excretion of microalbumin in the urine. The decrease in blood pressure was the same in both treatment groups, both according to the data of routine blood pressure measurements and according to the data of 24-hour monitoring. Creatinine clearance, glycemic control, and blood lipid levels did not change significantly throughout the study.The number of patients who dropped out of the study due to the development of side effects also did not differ between treatment groups. Thus, therapy with an ACE inhibitor turned out to be preferable for the treatment and prevention of diabetic nephropathy [28].
When comparing the effectiveness of lisinopril and the calcium channel blocker manidipine, it turned out that with a comparable hypotensive effect, the drugs have different effects on renal function and left ventricular myocardial hypertrophy. The study included 174 patients with arterial hypertension (DBP 80-100 mm Hg).Art.) and T2DM and microalbuminuria. Therapy was started with 10 mg of lisinopril or 10 mg of manidipine per day. If after 8 weeks the DBP remained above 80 mm Hg. Art., the dose of drugs was doubled. If after another three months the target level of DBP was not achieved or side effects were recorded in patients, therapy was discontinued and patients were excluded from the analysis. The entire observation period was 24 months. 99 patients completed their observation. It turned out that both drugs equally reduce SBP and DBP: manidipine – by 22.3 / 15.5 mm Hg.Art. and lisinopril – by 21.4 / 15.7 mm Hg. Art. Lisinopril caused a more significant decrease in the level of microalbuminuria – by 37.2 mg versus 29.9 mg per day, and this effect when taking lisinopril occurred earlier (after three months of treatment) than when treated with manidipine. More pronounced regression of left ventricular hypertrophy was observed during treatment with manidipine (-14.9 g / m2 versus -10.8 g / m2 during treatment with lisinopril) [29].
A prospective study investigated the effect of long-term (within 48 months) therapy with lisinopril and nisoldipine on the state of renal function in patients with type 1 diabetes.Blood pressure control was carried out using 24-hour monitoring, assessment of the degree of microalbuminuria and glomerular filtration rate. Lisinopril was prescribed at a dose of 10-20 mg, nisoldipine – 20-40 mg per day. The decrease in blood pressure was the same in both treatment groups, which was confirmed by 24-hour monitoring data. The decrease in the level of glomerular filtration was also identical in both groups. Moreover, only lisinopril caused a decrease in the excretion of albumin in the urine. Calcium channel blocker therapy did not affect the degree of microalbuminuria [30].
The aim of the candesartan and lisinopril microalbuminuria study was to compare the efficacy of monotherapy with candesartan, lisinopril and combination therapy with these two drugs in patients with hypertension, microalbuminuria and T2DM. Patients received lisinopril 20 mg or candesartan 16 mg daily for 12 weeks. Then monotherapy or combined treatment with these two drugs continued for another 12 weeks. The main parameters by which the effectiveness of therapy was assessed were the level of blood pressure and the level of microalbuminuria.A total of 199 patients were included in the study. The main criteria for the inclusion of the patient in the study were diastolic blood pressure 90-110 mm Hg. Art. and a creatinine / albumin ratio of 2.5-25 mg / mol after two weeks of placebo. Patients with secondary types of hypertension, severe obesity (BMI> 40 kg / m2), and renal failure were not included in the study. After 12 weeks of treatment, it turned out that the decrease in blood pressure was the same in the groups of patients receiving monotherapy with candesartan and lisinopril.In the lisinopril group, SBP decreased by 15.7 mm Hg. Art., DBP – by 9.7 mm Hg. Art., the ratio of creatinine / albumin decreased by 46%. In the candesartan group, the decrease in these indicators was 12.4 mm Hg, respectively. Art., 9.5 mm Hg. Art. and 30%. With the same decrease in blood pressure, lisinopril reduced urinary albumin excretion to a greater extent, although this tendency was not significant (p = 0.058). After the first 12 weeks of treatment, one third of patients continued monotherapy with lisinopril, one third received monotherapy with candesartan, and one third received combination therapy with these two drugs.In terms of its effect on blood pressure, the combination therapy was found to be more effective than monotherapy with any of the drugs. In the combination therapy group, the regression of microalbuminuria was also the most significant – by 50%. Moreover, the combination therapy was significantly more effective than candesartan (p = 0.04). When compared with monotherapy with lisinopril, there were no significant differences in the effect on the excretion of microalbumin [31].
A similar study was conducted with another angiotensin receptor blocker, telmisartan.The authors compared the effectiveness of monotherapy with 20 mg lisinopril per day, 80 mg of telmisartan per day and a combination of these two drugs in patients with T2DM, microalbuminuria, and arterial hypertension. Both drugs significantly reduced systolic and diastolic blood pressure and decreased urinary albumin excretion. The combination treatment was more effective than monotherapy with either drug [32].
The aim of the Long-Term Dual Blockade With Candesartan and Lisinopril in Hypertensive Patients With Diabetes (CALM II) study was to compare the effect of combination therapy with candesartan and lisinopril with high-dose lisinopril monotherapy on systolic blood pressure in patients with hypertension and diabetes.The study design was double-blind with two active treatment groups. Patients were randomized to receive lisinopril 40 mg or a combination of lisinopril 20 mg and candesartan 16 mg per day. The observation period was 12 months. The effectiveness of therapy was assessed according to the data of daily monitoring of blood pressure. The study included 75 patients with hypertension and diabetes with systolic blood pressure 120-160 mm Hg. Art against the background of treatment with lisinopril at a dose of 20 mg for at least a month. In general, there were no significant differences between combination therapy and lisinopril therapy in terms of the effect on blood pressure.The combination of lisinopril and candesartan significantly improved daytime BP reduction. BP at night and average BP values ​​per day did not differ [Andersen NH, Poulsen PL, Knudsen ST et.al. Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes: the CALM II study. Diabetes Care. 2005 Feb; 28 (2): 273-7].
Side effects
The most common side effect of lisinopril treatment is dry cough. The frequency of this side effect, according to various sources, ranges from 4 to 18%.In this case, the risk of developing this undesirable phenomenon depends on the duration of the use of ACE inhibitors [34]. In a large post-marketing study in a cohort of 10,289 patients, it was shown that, in addition to dry cough, the most common side effects were dizziness (2.3%), headache (2.1%), weakness (1.7%), and nausea ( 1.0%) [35].
In a large population-based observational study, the ability of lisinopril to increase blood creatinine levels was analyzed. We analyzed the data of 18,977 patients who were prescribed lisinopril for 6 months.13,166 of them had data on the level of creatinine before the start of treatment and after 6 months of therapy. A significant increase in creatinine was considered to be an increase from normal values ​​(less than 1.2 mg / dL) to 2.5 mg / dL and above. Such a significant increase in the level of creatinine was noted in 31 patients from the examined group. None of these patients had end-stage renal failure, although three patients died during the follow-up period. A significant increase in creatinine levels, as a rule, was associated with severe heart failure, dehydration, or the presence of competing diseases [36].
Study ALLHAT: the Antihypertensive and Lipid-Lowering Treatment to vent Heart Attack Trial
The largest study investigating the effectiveness of lisinopril in patients with hypertension was the ALLHAT study, the results of which were discussed in detail earlier [37, 38].
In total, in the ALLHAT study, 15,255 patients received chlorthalidone at a dose of 12.5-25 mg, 9048 patients received amlodipine at a dose of 2.5-10 mg, and 9054 patients received lisinopril at a dose of 10-40 mg per day.If the target blood pressure level could not be reached, then at the next stage a second drug was added (atenolol – 25-100 mg, reserpine – 0.05-0.2 mg once a day or clonidine – 0.1-0.3 twice a day ). If there was no effect at the third stage, hydralazine was added – 25-100 mg twice a day.
Neither of these three drugs has been shown to be beneficial in preventing the so-called primary combined endpoint (myocardial infarction and death from cardiovascular causes).Analysis of all-cause mortality also did not reveal any benefits of any drug. Lisinopril was somewhat inferior to chlorthalidone in its ability to prevent strokes, hospitalizations for angina pectoris and worsening of the course of heart failure. Perhaps this is due to the fact that lisinopril in general reduced blood pressure somewhat worse than chlorthalidone (SBP – by 4 mm Hg and DBP – by 2 mm Hg). The differences were especially large in individuals of the Negroid race, characterized by low sensitivity to ACE inhibitors.Overall, treatment with lisinopril in white patients in the ALLHAT study was more successful. Thus, lisinopril significantly exceeded amlodipine in preventing the decompensation of heart failure in whites; in patients of the Negro race, the effectiveness of lisinopril and amlodipine did not differ significantly.
The most interesting results of the study include data on the reduction in the risk of developing new cases of diabetes mellitus in patients who received lisinopril, compared with patients who received chlorthalidone [39].The incidence of new cases of diabetes detected after two years of treatment was almost twice as high in patients treated with chlorthalidone compared with patients treated with lisinopril. The same trend persisted four years after the start of treatment. In patients taking lisinopril, the blood glucose level was lower. These differences became significant after two years of the study and remained statistically significant until the end of the study.
Similar results were found with the use of angiotensin receptor blockers.The valsartan group in the VALUE study had a lower risk of new cases of diabetes than the amlodipine group, and the losartan group in the LIFE study had fewer new cases of diabetes than the atenolol group [40, 41]. Similar results were obtained for ramipril versus placebo in the HOPE study [42] and for captopril versus diuretics and b-blockers in the CAPP study [43]. Thus, a similar effect of ACE inhibitors and BAR is manifested not only when compared with thiazide diuretics, known for their effect on carbohydrate metabolism, but also with drugs from other groups – calcium antagonists, b-blockers.Most often, this effect is associated with a blockade of the renin-angiotensin system, however, the mechanism of the effect of ACE inhibitors and BAR on the prevention of the development of insulin resistance is not completely clear.
As part of the ALLHAT study, a genetic sub-study GenHAT was conducted to determine whether genetic markers affect the effectiveness of antihypertensive therapy. The first results of the GenHAT study have already been published. The main candidate gene for the efficacy of lisinopril was the angiotensin converting enzyme (ACE) gene and its type I / D polymorphic marker.Earlier it was shown that carriers of the D allele have a higher level of expression of the ACE gene and a higher activity of the renin-angiotensin system. Carriage of the D allele is believed to predispose to the development of cardiovascular complications. In the GenHat study, no association of this allele with the effectiveness of lisinopril therapy was found [44].
Other indications for the appointment of lisinopril
In addition to arterial hypertension, indications for the appointment of lisinopril may be myocardial infarction (MI) and heart failure.
Study GISSI-3 (Gruppo Italiano per lo Studio della Sopravvivenzanell’Infarto miocardico) was devoted to the study of the effectiveness of lisinopril, nitrates and their combination in patients with acute myocardial infarction. IV therapy with nitroglycerin or lisinopril was started no later than 24 hours after the onset of myocardial infarction symptoms. The dose of lisinopril was 5 mg per day. It turned out that only in the group of patients receiving lisinopril there was a significant decrease in mortality and, in addition, in the lisinopril group, the risk of developing severe left ventricular dysfunction decreases, and its remodeling improves [45].
One study that directly compared two ACE inhibitors in MI was the SMILE-2 (Survival of Myocardial Infarction) study, which compared the efficacy of zofenopril 30-60 mg versus lisinopril 5-10 mg per day. Both drugs were prescribed to patients receiving thrombolytic therapy for acute myocardial infarction. Therapy with ACE inhibitors began no later than 12 hours after the end of thrombolysis and lasted 42 days. A total of 1024 patients were included in the study.There were no significant differences in the risk of cardiovascular complications in both treatment groups [46].
The ATLAS (Assessment of Treatment with Lisinopril And Survival) study compared the efficacy of high and low doses of lisinopril in the treatment of heart failure. The greatest decrease in the risk of new hospitalizations due to worsening of heart failure – by 24% in the group of patients receiving high doses of the drug [47, 48].
Thus, lisinopril is one of the reference ACE inhibitors.It has been proven to be highly effective in patients with arterial hypertension, diabetes mellitus, and target organ damage. This gives grounds for wider use of the drug in the treatment of these diseases.

Literature

Lisinopril: instructions for use against pressure, analogs

What is the pressure to take Lisinopril? What does it help from? What dosage should be followed? Are Lisinopril pressure pills effective for hypertension? Similar questions are asked by people who have encountered arterial hypertension.

Today we will talk about a drug that belongs to the group of ACE inhibitors. Since taking medication leads to the expansion of blood vessels, Lisinopril for hypertension will become indispensable helpers in the fight against the disease.

The drug does not affect the heart rate, effectively reduces systolic and diastolic pressure.

Pharmaceutical companies produce Lisinopril in the form of tablets with different dosages: 5 mg, 10 mg and 20 mg. One package can contain 20, 30, 50 or 60 tablets.

The active substance is lisinopril dihydrate, and the auxiliary components are milk sugar, pregelatinized starch, talc, magnesium stearate and colloidal silicon dioxide (aerosil).

This drug, as already mentioned, belongs to a group of drugs whose work is aimed at inhibiting the action of the angiotensin-converting enzyme (ACE). The main effect of Lisinopril, which has hypotensive, vasodilatory, cardioprotective and natriuretic effects, is to reduce the transformation of angiotensin-1 into angiotensin-2.

Lisinopril stimulates the formation of prostaglandins, reduces the degradation of bradycardin and reduces the amount of released aldosterone.As a result of these pharmacological properties, the drug reduces blood pressure to acceptable values, increases the volume of blood pumped by the heart per minute, reduces the strength of the peripheral resistance of blood vessels, and increases the resistance of the heart muscle to functional loads.

Also, Lisinopril reduces the pressure in the capillaries of the lungs. With prolonged use, the hypertrophy of the walls of the arteries and myocardium decreases. It is worth paying attention to the fact that Lisinopril promotes the excretion of sodium salts from the body.

The maximum pharmacological effect of Lisinopril tablets is observed two weeks after the start of drug therapy. If the result is not observed in the treatment of hypertension, then the reception is combined with other antihypertensive drugs.

It is not recommended to use Lisinopril tablets if the systolic pressure is below 100 points.

Recall that high normal blood pressure is characterized by indicators 130-139 / 85-98, the first degree of hypertension – 140-159 / 90-99, the second – 160-179 / 100-109, and the third from 180/110 mm Hg.Art.

The antihypertensive effect is observed already after 1-3 hours from the moment of taking the pill, and the peak – after 6 hours. The duration of the hypotensive effect is recorded within a day. The stable effect of the drug is observed in the second or third week of treatment.

In the case of a sharp refusal from the drug Lisinopril, a sudden increase in pressure is not observed, as well as an excess of the values ​​that were before the start of therapy.

Dilatation of arterioles and veins can reduce blood pressure by Lisinopril by 15%The bioavailability of the drug after oral administration reaches 29%. This indicator is not affected by the functional state of the liver. Food intake does not correct drug absorption. The active substance of Lisinopril, being in the human body, is not metabolized. It is excreted unchanged in the urine.

Lisinopril is recommended to be taken if the patient has encountered:

Since the persistent therapeutic effect of the drug Lisinopril occurs after 2-4 weeks of administration, it is not used for hypertensive crisis in order to quickly bring down the pressure.Since the drug has a prolonged effect, it is enough to take a pill once a day. It is better to do this in the morning with a sufficient amount of liquid (100 ml). The treatment regimen should be prescribed by a doctor, taking into account the patient’s age and the presence of various chronic diseases.

In arterial hypertension, if the patient is not taking other antihypertensive drugs, Lisinopril is prescribed 5 mg once a day. In the absence of side effects, the dosage is increased by 5 mg over the next three days.A dosage of 20 mg is able to support drug therapy for hypertension. The maximum permissible daily dose of the active substance is 40 mg. If the patient is taking diuretic pills, then they should be discarded, and taking Lisinopril begins only three days later (initial dosage of 5 mg). During the first hours after taking the drug, it is recommended to observe the attending physician.

Lisinopril with renovascular hypertension is taken at 2.5-5 mg at a time in 24 hours. Regular monitoring of blood pressure indicators, potassium concentration in the blood, and kidney function is carried out.In the case of long-term therapy, the dosage is assigned individually. Patients in the elderly are prescribed a dose of 2.5 mg.

In renal failure, if creatine clearance rates reach 30-70 ml per minute, Lisinopril is taken at 5-10 mg. When the CC is 10-30, then the remedy for pressure is taken at 2.5-5 mg per knock.

In the case of diabetic nephropathy, with constant intake of insulin, Lisinopril is prescribed 10 mg per day, and in case of complications – up to 20 mg.

In the treatment of myocardial infarction, Lisinopril is used in complex therapy. Reception starts with 5 mg, then 10 mg per day is respected.

Lisinopril under reduced pressure is prescribed at 2.5 mg. In consultation with a doctor, the dosage can be increased to 5 mg, gradually lowering it to minimum values.

The drug Lisinopril is contraindicated in cases where the patient has encountered:

In the latter case, if taking Lisinopril is necessary, the child is transferred to artificial feeding.

Precautions include:

Before starting drug therapy, you should consult with your doctor to find out at what pressure to take Lisinopril and what dosage to follow.

Subject to the dosage and the correct treatment regimen, the negative consequences after taking Lisinopril, as a rule, disappear within a few days. However, it is important to know what side effects the patient may be experiencing. It is about:

During the period of the medication course, the intake of drinks and preparations containing ethanol is excluded.The fact is that Lisinopril enhances the negative effects of alcohol on the body. Ignoring this recommendation can lead to violations of the liver function.

How does Lisinopril interact with other drugs? To exclude undesirable consequences, the drug is not taken simultaneously with potassium-sparing diuretics, antacids, sympathomimetics, adrenostimulants, Indomethacin, antipsychotics, quinine.

In case of excessive intake of lisinopril dihydrate, the patient runs the risk of tachycardia, a sharp decrease in pressure, relaxation of vascular smooth muscles (peripheral).To provide first aid to the victim, the stomach is washed, given activated charcoal, placed on the back so that the legs are above the level of the head.

With a sharp decrease in blood pressure, Dopamil is used. It is important to pay attention to the fact that hemodialysis in the described situation is ineffective. In case of an overdose of Lisinopril, it is necessary to seek medical help from a specialist as soon as possible.

Like the first generation inhibitor Captopril, the drug Lisinopril is a group of direct-acting drugs.The rest of the antihypertensive drugs become active as a result of metabolism. Therefore, as an analogue of Lisinopril, it is impractical to consider them in view of other pharmacodynamics.

Medicines of similar action should include:

Tatiana, 42 years old

My father is hypertensive. Arterial hypertension has not escaped me either. Recently, the pressure began to rise to 160/100. I consulted with a local therapist.The doctor said that it is better not to waste time and start treatment. To control the disease in the early stages, I selected an effective treatment. Prescribed to take Lisinopril pressure pills daily at a dosage of 5 mg (once a day). For a beginner with hypertension, such an amount, as noted by the doctor, will be enough. The first few days did not feel any special effect. After a week, the pressure did not rise above 135/90. To be honest, it is not difficult to take one pill every day to live a normal life.I do not observe any side effects. I made sure that Lisinopril reduces blood pressure.

Larisa, 38 years old

At the age of 29, I found out that I have grade 3 hypertension. I was in the hospital, blood pressure was knocked down with injections and drugs. At times it rose to 240/160. I tried different pills, but nothing really helped. A woman pharmacist advised me to use Lisinopril for blood pressure. The first three days I took 10 mg 3 times a day. BP dropped to 160/120. After a month of use, I reduced the daily dose to 10 mg.My blood pressure became stable, staying at the level of 140/100. The work of the heart has improved. I have been taking the drug for 7 years. Everything is completely satisfactory. The only negative is the appearance of depression.

Maria, 53 years old

She took blood pressure pills (ACE inhibitor group) for a long time.