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.

Lisinopril tablets

What is this medicine?

LISINOPRIL (lyse IN oh pril) is an ACE inhibitor. This medicine is used to treat high blood pressure and heart failure. It is also used to protect the heart immediately after a heart attack.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

COMMON BRAND NAME(S): Prinivil, Zestril

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• diabetes
• heart or blood vessel disease
• kidney disease
• low blood pressure
• previous swelling of the tongue, face, or lips with difficulty breathing, difficulty swallowing, hoarseness, or tightening of the throat
• an unusual or allergic reaction to lisinopril, other ACE inhibitors, insect venom, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on your prescription label. You may take this medicine with or without food. If it upsets your stomach, take it with food. Take your medicine at regular intervals. Do not take it more often than directed. Do not stop taking except on your doctor’s advice.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed. While this drug may be prescribed for children as young as 6 years of age for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What may interact with this medicine?

Do not take this medicine with any of the following medications:

• hymenoptera venom
• sacubitril; valsartan

This medicines may also interact with the following medications:

• aliskiren
• angiotensin receptor blockers, like losartan or valsartan
• certain medicines for diabetes
• diuretics
• everolimus
• gold compounds
• lithium
• NSAIDs, medicines for pain and inflammation, like ibuprofen or naproxen
• potassium salts or supplements
• salt substitutes
• sirolimus
• temsirolimus

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular check ups. Check your blood pressure as directed. Ask your doctor what your blood pressure should be, and when you should contact him or her.

Do not treat yourself for coughs, colds, or pain while you are using this medicine without asking your doctor or health care professional for advice. Some ingredients may increase your blood pressure.

Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information.

Check with your doctor or health care professional if you get an attack of severe diarrhea, nausea and vomiting, or if you sweat a lot. The loss of too much body fluid can make it dangerous for you to take this medicine.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this drug affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol can make you more drowsy and dizzy. Avoid alcoholic drinks.

Avoid salt substitutes unless you are told otherwise by your doctor or health care professional.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the hands, feet, face, lips, throat, or tongue
• breathing problems
• signs and symptoms of kidney injury like trouble passing urine or change in the amount of urine
• signs and symptoms of increased potassium like muscle weakness; chest pain; or fast, irregular heartbeat
• signs and symptoms of liver injury like dark yellow or brown urine; general ill feeling or flu-like symptoms; light-colored stools; loss of appetite; nausea; right upper belly pain; unusually weak or tired; yellowing of the eyes or skin
• signs and symptoms of low blood pressure like dizziness; feeling faint or lightheaded, falls; unusually weak or tired
• stomach pain with or without nausea and vomiting

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• changes in taste
• cough
• dizziness
• fever
• headache
• sensitivity to light

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from moisture. Keep container tightly closed. Throw away any unused medicine after the expiration date.

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

Prinivil, Zestril (lisinopril) dosing, indications, interactions, adverse effects, and more

7 Lisinopril Side Effects To Know If You Have High Blood Pressure

When you get stuck behind a driver who forgot green means go, when your friend cancels dinner plans after you’re already at the restaurant, when the person in front of you scores the last chocolate chip muffin you totally had your eye on—all legit reasons for your blood pressure to skyrocket.

Hopefully these are just short-term elevations, but if not, you’re not alone. Chronic high blood pressure affects about one in five women under 32, according to the National Institutes of Health.

If you have high blood pressure, first, kudos for actually knowing it. It’s often called “the silent killer” because on its own, high blood pressure doesn’t show any symptoms and yet can lead to serious problems, including death.

From there, treating high blood pressure, especially in young women, is normally a combination of lifestyle changes—namely diet, exercise, sleep, and stress management, says Adam Splaver, M. D., a cardiologist with NanoHealth Associates in South Florida.

But, if your lifestyle choices are already pretty optimal and you’re still struggling with high blood pressure, your doctor may prescribe you lisinopril—an angiotensin-converting enzyme (ACE) inhibitor—an one of the most common medications used to manage high blood pressure.

The drug works by helping decrease tightness in blood vessels, allowing blood to flow more smoothy and the heart to pump blood more efficiently. Though the drug is super helpful in controlling high blood pressure, there are still some strange side effects to watch out for.

1. You’re not sick, but you’ve got a cough that just won’t quit.

A “non-productive” cough (i.e., a cough that doesn’t bring anything up, like mucous or blood) is one of the most common side effects of lisinopril, says Splaver. It’s weird and annoying, but it’s not dangerous, he adds. However, if it’s really bothering you, definitely bring it up with your doctor, as there are other meds you can try.

2. You feel exhausted and, weirdly enough, kind of tingly.

Lisinopril can cause your potassium levels to skyrocket, a potentially dangerous side effect, says Splaver. That’s because you won’t necessarily know your potassium levels are rising at first, but if they get high enough, they can make you feel exhausted, numb, or tingly.

Splaver says your doctor should do a routine blood test to check your levels one to two weeks after starting the drug to make sure your body is handling it well. If your doctor hasn’t recommended blood tests yet, or if you start to feel strange, call and get a test scheduled asap.

3. Your head is literally always pounding.

Headaches can happen for a myriad of reasons, but if you develop an unrelenting headache, it may be due to the lisinopril. Headaches are the most commonly reported side effect of the drug, according to the NIH. If they’re mild or go away on their own, don’t worry about it. But if they persist, it’s time to give your doctor a call, says Splaver.

4. You know (and use) every bathroom in a 2-mile radius.

Lisinopril dilates your arteries—that’s how it works to lower high blood pressure—but this can affect other parts of your body besides your heart, especially your kidneys. If you already have kidney problems or are prone to getting them, this drug can make them worse, says Splaver.

At first, you likely won’t feel any symptoms, but if you notice changes in how frequently you have to pee or what your pee looks like, along with pain when using the bathroom, lower back pain, or other signs of kidney problems, call your doctor right away, he says.

5. You’re having trouble orgasming.

A decrease in sexual ability is one of the top five most commonly reported side effect of lisinopril, according to the NIH. That’s because your sexual response depends a lot on blood flow to your genitals, so anything that messes with your arteries and blood flow can mess up your orgasms, says Splaver. Call your doctor if you feel like the drug is hurting your sex life, as there are other medical options you can try.

6. You feel really dizzy whenever you go from sitting to standing.

You know that feeling when you stand up quickly and the room starts spinning? That’s actually caused by a rapid drop in blood pressure upon standing (a.k.a orthostatic hypotension) and can cause cause you to feel dizzy, nauseous, or even black out.

Lisinopril can bring this on or make it worse if you are already prone to it, says Splaver. If you’re just dizzy, practice standing up really slowly until you regain your equilibrium—and make sure you’re staying hydrated. If you’re actually fainting, however, it’s time to go back in and see your doctor, he adds.

7. Your face swells up unexpectedly.

Swelling around your face and lips (a.k.a. angioedema) is a rare but potentially serious side effect of lisinopril. If the swelling gets bad enough, it can cause your throat or tongue to block you airway, according to the Mayo Clinic.

If you’re going to get angioedema from lisinopril, it’ll most likely happen shortly after taking the first dose. However, it can occur even after weeks of being on the medication, says Splaver. If you experience swelling and difficulty breathing, call 911 immediately.

This content is created and maintained by a third party, and imported onto this page to help users provide their email addresses. You may be able to find more information about this and similar content at piano.io

Lisinopril Blood Pressure Medicine Side Effects

Lisinopril is an ACE inhibitor used to treat high blood pressure. It may also be used to treat heart failure in combination with other drugs. This drug may cause side effects that are bothersome or persistent. In some cases, these side effects may be severe enough to require a dosage adjustment or replacement of lisinopril with an alternate drug.

Skin Changes

Lisinopril may cause itching or a mild rash on the skin. This is usually a minor side effect that will clear up on its own. However, a rash can also indicate an allergic reaction. If the rash is accompanied by redness, swelling of the face or difficulty breathing, seek immediate medical attention. One of the more serious side effects of lisinopril is yellowing of the eyes and skin. If this occurs, seek the advice of a medical professional.

General Side Effects

There are several general side effects of lisinopril that affect the entire body. They include weakness, light-headedness and dizziness. If light-headedness is persistent or fainting occurs, seek medical attention; these are serious side effects that could indicate a serious medical condition.

Urinary System

Lisinopril can affect the urinary system in several ways. Protein in the urine and worsening of kidney disease have been reported. Lisinopril can also cause the levels of blood urea nitrogen and creatinine to increase. Painful urination, reduced frequency of urination, urinary tract infection and inability to urinate may occur.

While metabolic side effects of lisinopril are rare, they can occur in some patients. The levels of potassium and serum aldosterone may increase with lisinopril therapy. People who take lisinopril with diabetic medications may experience low blood sugar levels. This medication may also lead to weight gain, weight loss, gout and fluid overload.

Nervous System

Some side affects of lisinopril affect the nervous system and how it interprets sensations. This drug can cause tremors, nerve pain, tingling sensations and spasms. Lisinopril has also been linked to memory impairment.

Cardiovascular System

Lisinopril has a number of side effects that affect the cardiovascular system. It can cause orthostatic hypotension, low blood pressure, edema and inflammation of the blood vessels. Lisinopril has also been linked to heart attack, cardiac arrest, pulmonary embolism, heart arrhythmia and stroke.

Respiratory System

The respiratory system can be affected by treatment with lisinopril. The drug has been associated with bronchitis, nosebleed, laryngitis, wheezing, pharyngitis, pleural effusion, rhinitis and coughing up blood.

Digestive System

Digestive system side effects are common with lisinopril treatment. The drug can cause gastrointestinal cramping, flatulence, constipation, heartburn, dry mouth, indigestion, vomiting and stomach inflammation. It has also been linked with hepatitis and pancreatitis.

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

North Harrow

Middlesex HA1 4HF

United Kingdom

Lisinopril instructions for use: indications, contraindications, side effects – description Lisinopril tab. 10 mg: 20 pcs. (37444)

Most often, a pronounced decrease in blood pressure occurs with a decrease in BCC caused by diuretic therapy, a decrease in salt intake, dialysis, diarrhea or vomiting. In patients with CHF with or without concurrent renal failure, a pronounced decrease in blood pressure is possible.

Patients with coronary artery disease, cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke, lisinopril should be prescribed only under the strict supervision of a physician.Transient arterial hypotension is not a contraindication for taking the next dose of lisinopril.

When using lisinopril, some patients with CHF, but with normal or low blood pressure, may experience a decrease in blood pressure, which is usually not a reason for discontinuing treatment.

In CHF, the resulting severe arterial hypotension can lead to a deterioration in renal function. In some cases, in the presence of CHF with normal or low blood pressure, lisinopril can also cause an additional decrease in blood pressure.This effect is not a contraindication for further administration of lisinopril.

In patients with bilateral renal artery stenosis or stenosis of an artery of a solitary kidney, during treatment with ACE inhibitors, in some cases, an increase in the concentration of urea nitrogen in the blood plasma and serum creatinine was observed. These changes were almost always reversible and disappeared after the withdrawal of the ACE inhibitor. These complications are especially common in patients with pre-existing renal impairment.If the patient has renovascular hypertension, the risk of severe arterial hypotension and renal failure is increased. In this category of patients, treatment should be started with lower doses of lisinopril under medical supervision.

Since the simultaneous use of diuretics is an additional risk factor for the development of arterial hypotension, they should be canceled and kidney function should be monitored during the first week.

An increase in the concentration of urea nitrogen in blood plasma and serum creatinine was also observed in patients with arterial hypertension without concomitant renal dysfunction, especially with the simultaneous use of lisinopril and diuretics.These changes were mild, and the indicators returned to normal after discontinuation of lisinopril or a diuretic.

In patients with acute myocardial infarction, therapy with lisinopril should not be started if there are signs of impaired renal function, expressed in an increase in blood plasma CC above 177 μmol / l and / or proteinuria above 500 mg / day. If impaired renal function develops while taking lisinopril (CC in the blood plasma is higher than 265 μmol / l or doubles relative to the values ​​before the start of therapy), then it is necessary to consider the possibility of canceling lisinopril.Treatment with lisinopril for acute myocardial infarction is carried out against the background of standard therapy (thrombolytics, acetylsalicylic acid (as an antiplatelet agent), beta-blockers). Lisinopril can be used with a solution of nitroglycerin for intravenous administration or with the use of nitroglycerin sublingually.

It is not recommended to use lisinopril in patients after acute myocardial infarction if systolic blood pressure does not exceed 100 mm Hg.

When using drugs that lower blood pressure in patients with major surgery or during general anesthesia, lisinopril can block the formation of angiotensin II, secondary to compensatory renin release.Before surgery (including dental surgery), you should stop taking lisinopril 24 hours before and inform the surgeon / anesthetist about the use of an ACE inhibitor.

It is assumed that the simultaneous administration of ACE inhibitors and insulin, as well as hypoglycemic drugs for oral administration, may lead to the development of hypoglycemia. The greatest risk of development is observed during the first weeks of combination therapy, as well as in patients with impaired renal function.Patients with diabetes mellitus require careful glycemic control, especially during the first month of ACE inhibitor therapy.

Before starting treatment, it is necessary to compensate for the loss of fluid and salts. In patients with risk factors for the development of symptomatic arterial hypertension (patients on a diet with limited salt intake with or without hyponatremia, patients with hypovolemia or receiving diuretic therapy), these conditions should be corrected, if possible, before starting treatment with lisinopril.Risk factors for the development of hyperkalemia include chronic renal failure, diabetes mellitus and concomitant use of potassium-sparing diuretics (spironolactone, eplerenone, triamterene, or amiloride), potassium preparations or salt substitutes containing potassium ions, and the use of drugs that are associated with an increase in potassium in blood plasma (for example, heparin). Periodic monitoring of plasma potassium is recommended.

Angioneurotic edema of the face, limbs, lips, tongue, mucous membranes, epiglottis and / or larynx was observed with the use of ACE inhibitors, incl.including preparations containing lisinopril. This side effect can occur at any stage of therapy. In such cases, it is necessary to urgently cancel the use of lisinopril and prescribe adequate therapy. The patient should be under medical supervision until the symptoms of edema completely regress. It should be borne in mind that even in cases where only swelling of the tongue is noted, the patient should be under medical supervision, since therapy with antihistamines and corticosteroid drugs may be insufficient.

Patients who have previously undergone respiratory surgery have a higher risk of developing angioedema of the larynx or tongue.

Patients who have had angioedema not associated with taking an ACE inhibitor are at greater risk of developing this complication when taking an ACE inhibitor. It should be borne in mind that the use of ACE inhibitors in patients of the Negroid race entails a higher risk of developing angioedema. The effectiveness of ACE inhibitors in reducing blood pressure in patients of the black race is lower than in representatives of other races.This effect is possibly associated with a pronounced predominance of low-rootin status in patients of the Negroid race with arterial hypertension.

Patients taking ACE inhibitors during hymenoptera venom desensitization rarely develop life-threatening anaphylactoid reactions. This can be avoided by temporarily stopping treatment with an ACE inhibitor before each desensitization procedure.

Dry cough that occurs with the use of ACE inhibitors is unproductive, persistent and resolves after stopping treatment.In the differential diagnosis of cough, its possible relationship with ACE inhibitors should be taken into account.

Very rarely, there have been cases of the development of a syndrome that began with the development of cholestatic jaundice, progressed to fulminant necrosis and, in some cases, was fatal. The mechanism for the development of this syndrome is not clear. The use of lisinopril in patients with signs of jaundice or a significant increase in the activity of hepatic transaminases should be discontinued and appropriate monitoring of laboratory parameters and the patient’s condition should be carried out.

There have been cases of neutropenia / agranulocytosis, thrombocytopenia and anemia while taking ACE inhibitors. Such cases are quite rare in patients with normal renal function. Neutropenia and agranulocytosis disappear after discontinuation of ACE inhibitors. Lisinopril should be used with extreme caution in patients with systemic connective tissue diseases receiving immunosuppressive therapy, treatment with allopurinol or procainamide, or these risk factors are present simultaneously, especially in patients with impaired renal function.In some cases, such patients may develop infectious diseases that are resistant to antibacterial therapy. In the case of using the drug in such patients, regular monitoring of blood leukocytes should be carried out.

If any symptoms of infection (eg, sore throat, fever) appear, the patient should see a doctor immediately, as they may be a manifestation of neutropenia.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors.At the same time, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and at a normal level of C1-esterase. Diagnosis is by abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when conducting differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Influence on the ability to drive vehicles and mechanisms

During the period of treatment, one should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions, since weakness or dizziness may develop, especially at the beginning course of treatment.

90,000 Lisinopril and carvedilol reduce the likelihood of discontinuing chemotherapy with trastuzumab in breast cancer patients

One of the most aggressive forms of breast cancer, HER2-positive, is most responsive to treatment with chemotherapy drugs such as trastuzumab and anthracyclines.Unfortunately, these drugs often have a pronounced toxic effect on cardiomyocytes. Cardiotoxicity may warrant the withdrawal of chemotherapy, which is effective from the point of view of cancer treatment.

The JACC journal published the results of a multicenter, randomized, double-blind, placebo-controlled study examining the effect of lisinopril or carvedilol on the development of cardiotoxicity during trastuzumab therapy for 12 months.The observation period was 2 years. The likelihood of stopping chemotherapy due to cardiotoxicity was also assessed. The criterion for cardiotoxicity is a decrease in LVEF by 10% (or by 5%, if initially this indicator is reduced by less than 50%).

The study included 468 women, whose average age was 51 ± 10.7 years. In the entire cohort of patients, the incidence of cardiotoxicity did not differ in the subgroups of lisinopril, carvedilol, or placebo. But if patients had previously received anthracyclines, therapy with carvedilol or lisinopril reduced the likelihood of developing cardiotoxicity (the incidence of this complication was 47% in the placebo group, 37% in the lisinopril group, 31% in the carvedilol group).In addition, against the background of the use of both lisinopril and carvedilol, cardiotoxicity developed later (respectively, OR 0.53 (95% CI 0.30 – 0.94; p = 0.015) and 0.49 (95% CI 0.27 – 0.89; p = 0.009)). While taking both lisinopril and carvedilol, trastuzumab was withdrawn significantly less frequently.

Thus, lisinopril and carvedilol reduce the likelihood of developing cardiotoxicity in the presence of trastuzumab in patients with HER2-positive breast cancer who were previously treated with anthracyclines.Preventive administration of such therapy may be considered with the aim of prolonging trastuzumab treatment.

Based on materials:

Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer. Maya Guglin, Jeffrey Krischer, Roy Tamura, et al. Journal of the American College of Cardiology Jun 2019, 73 (22) 2859-2868; DOI: 10.1016 / j.jacc.2019.03.495

http://www.onlinejacc.org/

Text: Ph.D. Shakhmatova O.O.

Arpimed

Interaction with other medicinal products

Amlodipine

Contraindicated drug combinations

Dantrolene (intravenous)

Cases of lethal ventricular fibrillation and collapse were observed in laboratory animals with the use of verapamil and intravenous dantrolene, accompanied by hyperkalemia.Due to the risk of developing hyperkalemia, concomitant administration of blockers of “slow” calcium channels, including amlodipine, should be excluded in patients prone to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

Combinations of drugs not recommended

Grapefruit juice

Taking amlodipine with grapefruit or grapefruit juice is not recommended, since in some patients the bioavailability of amlodipine may increase, which leads to increased blood pressure lowering effects.

Combinations of drugs requiring special care when using

Isoenzyme inductors SURZA4

There are no data on the effect of CYPZA4 isoenzyme inducers on the pharmacokinetics of amlodipine. The simultaneous administration of inducers of the CYPZA4 isoenzyme (for example, rifampicin, St. John’s wort preparations) and amlodipine can lead to a decrease in the plasma concentration of amlodipine. Care should be taken with the simultaneous use of the drug Gipomed and inducers of the isoenzyme SURZA4. Inhibitors of the isoenzyme SURZA4

Simultaneous administration of amlodipine and strong or moderate CYPZA4 inhibitors (protease inhibitors, for example, ritonavir, antifungal agents of the azole group, macrolides, for example, erythromycin or clarithromycin, verapamil or diltiazem) can lead to a significant increase in the concentration of amlodipine. The clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. In this regard, it may be necessary to monitor the clinical condition and adjust the dose of the drug Gipomed.

Combinations of drugs requiring caution when using

Simvastatin

Multiple administration of amlodipine at a dose of 10 mg in combination with simvastatin at a dose of 80 mg led to an increase in simvastatin exposure by 77% compared with simvastatin monotherapy. Thus, patients receiving amlodipine should take simvastatin in a daily dose not exceeding 20 mg.

Calcium preparations

May reduce the effect of BMCC.

Lithium preparations

With the combined use of BMCC with lithium preparations (there are no data for amlodipine), the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor or tinnitus) may increase.

Baclofen

Strengthening the antihypertensive effect. Blood pressure and renal function should be monitored, if necessary, the dose of amlodipine should be adjusted.

Amifostine

Possible enhancement of the antihypertensive effect of amlodipine.

Glucocorticosteroids

Decrease in antihypertensive action (retention of fluid and sodium ions as a result of the action of corticosteroids).

Tricyclic antidepressants, antipsychotics

There is an increased risk of orthostatic hypotension and increased antihypertensive effect (additive effect).

Tacrolimus

With simultaneous use with amlodipine, there is a risk of increasing the concentration of tacrolimus in blood plasma.In order to avoid the toxicity of tacrolimus when used simultaneously with amlodipine, the concentration of tacrolimus in the blood plasma of patients should be monitored and the dose of tacrolimus should be adjusted if necessary.

Tasonermin: with the simultaneous use of amlodipine can increase the systemic exposure of tasonermin in blood plasma. In such cases, regular monitoring of tasonermin in the blood and dose adjustment if necessary is necessary.

Other interactions with amlodipine

For the treatment of arterial hypertension, amlodipine can be safely used with thiazide diuretics, alpha-blockers, beta-blockers and ACE inhibitors .In patients with stable angina pectoris, it is possible to simultaneously use amlodipine with other antianginal drugs, such as long-acting and short-acting nitrates, beta-blockers .

Probably, an increase in the antianginal and antihypertensive effect of BMCC when used simultaneously with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as an increase in their antihypertensive effect when administered with alpha-1-blockers and antipsychotics.

Amlodipine does not cause a negative inotropic effect. However, some BMCCs can increase the severity of the negative inotropic effect of antiarrhythmic drugs that cause prolongation of the QT interval (eg, amiodarone and quinidine).

Unlike other BMCCs, there was no significant interaction between amlodipine (3rd generation BMCC) and NSAIDs, including indomethacin.

It is safe to prescribe amlodipine with oral hypoglycemic drugs. A single dose of sildenafil 100 mg in patients with essential arterial hypertension did not affect the pharmacokinetics of amlodipine.

Joint repeated administration of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg led to an insignificant change in the pharmacokinetic parameters of atorvastatin in a state of equilibrium concentration.

Ethanol (drinks containing alcohol): amlodipine has no significant effect on the pharmacokinetics of ethanol with single and repeated use at a dose of 10 mg.Interaction studies of cyclosporine and amlodipine in healthy volunteers and in special patient groups have not been conducted, with the exception of patients after kidney transplantation. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect, or increase the minimum concentration of cyclosporine to varying degrees up to 40%. The concentration of cyclosporine should be monitored in patients after kidney transplantation.

With the simultaneous use of amlodipine and digoxin, renal clearance and the concentration of digoxin in the blood serum do not change.

With the simultaneous use of warfarin with amlodipine, the prothrombin time does not change.

With the simultaneous use of with cimetidine , the pharmacokinetics of amlodipine does not change.

Amlodipine does not affect the degree of binding of digoxin, phenytoin, warfarin and indomethacin with blood plasma proteins in vitro .

Aluminum and magnesium-containing antacids: a single dose of such antacids together with amlodipine does not significantly affect the pharmacokinetics of amlodipine.

Lisinopril

Contraindicated drug combinations

Aliskiren

The simultaneous administration of ACE inhibitors with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and / or moderate or severe renal impairment (GFR less than 60 ml / min / 1.73 m ² body surface area) is contraindicated.

The administration of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy.

Combinations of drugs not recommended

Angiotensin 11 receptor antagonists (ARA II)

It has been reported in the literature that in patients with established atherosclerotic disease, chronic heart failure or diabetes mellitus with target organ damage, concomitant therapy with an ACE inhibitor and ARA II is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure) compared with the use of only one drug that affects RA AS.Double blockade (for example, when combined with an ACE inhibitor with ARA II) should be limited to individual cases with careful monitoring of renal function, potassium and blood pressure.

Potassium preparations, potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) or potassium-containing salt substitutes

The development of hyperkalemia (with a possible fatal outcome) is possible, especially with impaired renal function (additional effects associated with hyperkalemia). ACE inhibitors should not be used concomitantly with substances that increase the level of potassium in the blood plasma, except in cases of hypokalemia.The combination of lisinopril and the above agents is not recommended. If, nevertheless, the simultaneous use is shown, they should be used, observing precautions and regularly monitoring the content of potassium in the blood serum.

Lithium preparations

With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the concentration of lithium in the blood serum and associated toxic effects may be observed. The simultaneous use of lisinopril and lithium preparations is not recommended.If it is necessary to carry out such therapy, regular monitoring of the concentration of lithium in the blood serum should be carried out.

Combinations of drugs requiring special care when using

Insulin and oral hypoglycemic agents

Epidemiological studies have shown that the combined use of ACE inhibitors and hypoglycemic agents (insulins, hypoglycemic agents for oral administration) can enhance their hypoglycemic effect up to the development of hypoglycemia.This effect is most likely to be observed during the first weeks of simultaneous therapy, as well as in patients with impaired renal function.

Baclofen

Strengthens the antihypertensive effect of ACE inhibitors. You should carefully monitor the level of blood pressure and, if necessary, adjust the dose of antihypertensive drugs.

Diuretics

In patients taking diuretics, especially those that excrete fluids and / or salts, at the beginning of therapy with an ACE inhibitor, a significant decrease in blood pressure may be observed.The risk of developing antihypertensive effects can be reduced by discontinuing the diuretic, replenishing the loss of fluid or salts before starting therapy with ACE inhibitors. In case of arterial hypertension in patients with previous diuretic therapy, which could lead to excessive excretion of fluid and / or salts, diuretics should be canceled before using the drug Gipomed ^® .

Renal function (creatinine concentration) should be monitored in the first weeks of using the drug Gipomed ^® .

Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of ≥ 3 g / day

The simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, inhibitors of cyclooxygenase-2 (COX-2) and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors. The simultaneous use of drugs of ACE inhibitors and NSAIDs can lead to deterioration of renal function, including the development of acute renal failure and an increase in serum potassium, especially in patients with reduced renal function.Caution should be exercised when prescribing this combination, especially in elderly patients. Patients need to compensate for fluid loss and carefully monitor renal function, both at the beginning of treatment and during treatment.

Estramustine inhibitors mTOR (sirolimus, everolimus, temsirolimus), neutral endopeptidase inhibitors (omapatrilat, ipepatril, daglutril, sacubitril)

Concomitant use with ACE inhibitors is accompanied by an increased risk of angioedema.

DPP-4 inhibitors (glyptia)

Linagliptin, saxagliptin, sitagliptin, vildagliptin: when used together with ACE inhibitors, the risk of angioedema increases due to suppression of dipeptidyl peptidase-4 (DPP-1V) activity by gliptin.

Racecadotril (enkephalinase inhibitor used to treat acute diarrhea)

With simultaneous use with ACE inhibitors, the risk of developing angioedema may increase.

Combinations of drugs requiring caution when using

Other antihypertensive drugs (eg beta-blockers, slow calcium channel blockers, diuretics) and vasodilators

Possible enhancement of the antihypertensive effect of the drug. Caution should be exercised when administered concomitantly with nitroglycerin, other nitrates or other vasodilators, since this may further reduce blood pressure.

Antacids and cholestyramine

Concomitant use with antacids and cholestyramine leads to suppression of gastrointestinal absorption.

Tricyclic antidepressants, antipsychotics, general anesthetics, barbiturates, phenothiazine, ethanol

When taken together, it is possible to enhance the action of lisinopril.

Sympathomimetics

Sympathomimetics can weaken the antihypertensive effect of ACE inhibitors. Muscle relaxants

The simultaneous use of muscle relaxants with ACE inhibitors can lead to a marked decrease in blood pressure.

Gold preparations

When using ACE inhibitors, including lisinopril, by patients receiving intravenous gold (sodium aurothiomalate), rare cases of nitritoid reactions have been described (symptom complex, including facial flushing, nausea, vomiting and arterial hypotension).

Co-trimoxazole (sulfomethoxazole and trimethoprim)

Increased risk of developing hyperkalemia.

Selective serotonin reuptake inhibitors (escitalopram, paroxetine, fluoxetine, sertraline)

With simultaneous use with SSRIs, severe hyponatremia may develop.

Allopurinol, procainamide, cytostatics (5-fluorouracil, vincristine, docetaxel)

Development of leukopenia is possible.

Tissue plasminogen activators (alteplase, reteplase, tenecteplase)

Increased risk of angioedema when used simultaneously with ACE inhibitors.

Special instructions

On admission to the hospital, tell your doctor that you are taking Hypomed. When using the drug Gipomed, you should take into account the warnings regarding its individual components, given below.

Associated with amlodipine

Maintenance of dental hygiene and observation by the dentist is necessary (to prevent soreness, bleeding and gingival hyperplasia).

In elderly patients, T _1/2 may increase and the clearance of the drug may decrease. Dose changes are not required, but more careful monitoring of patients in this category is necessary.

The efficacy and safety of the drug Gipomed in hypertensive crisis have not been established.

Despite the absence of a “withdrawal” syndrome in BMCC, it is advisable to discontinue treatment with amlodipine by gradually decreasing the dose of the drug. Against the background of the use of amlodipine in patients with chronic heart failure, NYHA class III and IV of non-ischemic genesis, there was an increase in the incidence of pulmonary edema, despite the absence of signs of worsening heart failure.

Effects on fertility

In some patients receiving blockers of “slow” calcium channels, reversible biochemical changes in the sperm head were found, which may be clinically significant during IVF. However, there is currently no sufficient clinical data regarding the potential effect of amlodipine on fertility. A preclinical study identified undesirable effects on fertility in males.

Associated with lisinopripe

Symptomatic arterial hypotension

Most often, a significant decrease in blood pressure occurs with a decrease in circulating blood volume caused by the use of diuretics, a decrease in the amount of salt in food, dialysis, diarrhea or vomiting (see “Interaction with other drugs”, “Side effects”). In patients with chronic heart failure, in combination with or without renal failure, symptomatic hypotension may develop.It develops more often in patients with severe heart failure, which is associated with the use of high doses of diuretics, hyponatremia, or impaired renal function. Such patients require careful medical supervision (with careful selection of doses of lisinopril and diuretics). The same recommendations apply to patients with ischemic heart disease and cerebrovascular insufficiency, when a rapid decrease in blood pressure can lead to the development of myocardial infarction or stroke.

Patients with a pronounced decrease in blood pressure should be given a horizontal position; if necessary, an infusion of 0.9% sodium chloride solution is performed.Transient hypotension is not a contraindication to taking the next dose of lisinopril.

In patients with chronic heart failure with normal or low blood pressure, the use of lisinopril can lead to a decrease in blood pressure; as a rule, this does not require discontinuation of treatment. If arterial hypotension becomes symptomatic, the indications for a reduction in the dose of lisinopril or its cancellation should be evaluated.

In patients at risk of developing symptomatic arterial hypotension (patients on a salt-free or low-salt diet) with or without hyponatremia, as well as in patients receiving high doses of diuretics, these deviations (loss of water and salts) must be compensated before starting treatment …

It is necessary to control the effect of the starting dose of lisinopril on blood pressure.

Acute myocardial infarction

Standard treatment is recommended (thrombolytics, acetylsalicylic acid, beta-blockers).

Simultaneous use of lisinopril with intravenous administration of nitroglycerin or the use of transdermal nitroglycerin is possible.

In patients with acute myocardial infarction and the risk of further hemodynamic disturbances, deterioration after the administration of vasodilators, therapy with lisinopril should not be started.These patients include those with systolic blood pressure ≤ 100 mm Hg. Art. or cardiogenic shock. In patients with systolic blood pressure ≤ 120 mm Hg. Art. it is necessary to reduce the dose during the first 3 days after myocardial infarction. In patients with systolic blood pressure ≤ 100 mm Hg. Art. the maintenance dose should be reduced by up to 5 mg (or temporarily to 2.5 mg). In patients with persistent arterial hypotension (systolic blood pressure <90 mm Hg for 1 hour or longer), lisinopril should be discontinued.

Renal impairment

In patients with chronic heart failure, a significant decrease in blood pressure that occurs after the initiation of therapy with ACE inhibitors can lead to an aggravation of renal dysfunction.Cases of acute renal failure have been reported.

In patients with bilateral stenosis of the renal arteries or stenosis of the renal artery of a single kidney, cases of an increase in the concentration of urea and creatinine in serum associated with the use of ACE inhibitors have been reported; as a rule, these violations were transient and stopped after discontinuation of lisinopril. They were more common in patients with renal impairment.

Patients with acute myocardial infarction and significant renal impairment (serum creatinine concentration> 177 μmol / L and / or proteinuria> 500 mg / day) should not be prescribed lisinopril.With the development of impaired renal function during treatment with lisinopril (serum creatinine clearance> 265 μmol / l or its double increase compared to the baseline), the possibility of discontinuation of lisinopril should be considered.

Hypersensitivity, angioedema

In patients receiving ACE inhibitors, including lisinopril, rare cases of angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx were recorded, which could occur during any period of treatment.In such cases, it is necessary to immediately cancel lisinopril; observation of patients should be carried out until the symptoms disappear completely. Usually, cases of angioedema of the face and lips are temporary and do not require any treatment; possibly the appointment of antihistamines.

Angioedema of the larynx can be fatal. Angioedema of the tongue, epiglottis or larynx can lead to secondary obstruction of the airways, therefore it is necessary to immediately initiate appropriate therapy (0.3-0.5 ml of epinephrine (adrenaline) solution at a concentration of 1: 1000 subcutaneously) and / or take measures to ensure patency respiratory tract.

In rare cases, angioedema of the intestine developed during therapy with ACE inhibitors. At the same time, the patients had abdominal pain as an isolated symptom or in combination with nausea or vomiting, in some cases, without previous angioedema of the face and at a normal level of C1-esterase. The diagnosis was established by computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms disappeared after discontinuation of ACE inhibitors.Therefore, in patients with abdominal pain receiving ACE inhibitors, when conducting differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

In patients with a history of angioedema not associated with the use of ACE inhibitors, the use of ACE inhibitors may be associated with a higher risk of developing angioedema (see “Contraindications”).

Anaphylactic reactions associated with desensitization of hymenoptera venom

There are reports of very rare cases of life-threatening anaphylactic reactions that developed in patients taking ACE inhibitors during desensitization with hymenoptera venom.To prevent such cases, ACE inhibitors should be temporarily discontinued before desensitization.

Hemodialysis

Anaphylactic reactions have also been reported in patients undergoing hemodialysis using high permeability membranes (eg AM69) and concomitant administration of ACE inhibitors. In this group of patients, the use of other dialysis membranes or other antihypertensive drugs should be considered.

Cough

The use of ACE inhibitors may be associated with coughing. A dry cough that lasts for a long time, as a rule, disappears after the withdrawal of the ACE inhibitor. When carrying out a differential diagnosis, one should take into account the possibility of a cough associated with the use of ACE inhibitors.

Surgery / general anesthesia

The use of drugs that lower blood pressure during major surgery or general anesthesia may suppress the formation of angiotensin II in response to compensatory renin secretion.A significant decrease in blood pressure, which is considered as a result of this effect, can be controlled by reducing the volume of circulating blood.

Patients taking ACE inhibitors should inform their surgeon / anesthetist before undergoing surgery (including dental procedures).

Serum potassium

Cases of hyperkalemia have been reported.

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

If necessary, the simultaneous use of lisinopril and the above-mentioned drugs, care should be taken and the serum potassium content should be regularly monitored.

Double blockade RAAS

It has been proven that the simultaneous administration of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure).Thus, it is not recommended to prescribe ACE inhibitors, angiotensin II receptor blockers or aliskiren for double blockade of the RAAS.

If there are absolute indications for a double blockade of the RAAS, then it should be carried out under the close supervision of a specialist with frequent monitoring of blood pressure, renal function and electrolyte content.

The simultaneous use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and / or with moderate or severe renal failure (GFR less than 60 ml / min / 1.73 m2 of body surface area) and is not recommended in other patients.

The simultaneous use of ACE inhibitors with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

While taking ACE inhibitors, neutropenia / agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops.With extreme caution, the drug Gipomed should be prescribed to patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, or a combination of these risk factors, especially in patients with impaired renal function. Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing the drug Gipomed, such patients are recommended to periodically monitor the number of leukocytes in the blood plasma.Patients should inform their doctor about any sign of infectious disease (eg, sore throat, fever).

Mitral stenosis / aortic stenosis / hypertrophic cardiomyopathy

ACE inhibitors should be used with caution in patients with mitral stenosis, as well as in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic cardiomyopathy).

Liver failure

Very rarely, while taking ACE inhibitors, cholestatic jaundice occurs.With the progression of this syndrome, fulminant necrosis of the liver develops, sometimes with a fatal outcome. The mechanism for the development of this syndrome is unclear. If jaundice or a significant increase in the activity of “liver” enzymes occurs while taking ACE inhibitors, the drug Gipomed should be discontinued and the patient should be carefully monitored.

Ethnic differences

In patients of the Negroid race, angioedema develops more often than in representatives of other races while taking ACE inhibitors.ACE inhibitors may have a less pronounced antihypertensive effect in black patients than in other races. Perhaps this difference is due to the fact that in patients with arterial hypertension of the Negroid race, low renin activity is more often observed.

Influence on the ability to drive vehicles and work with mechanisms

There are no data on the effect on the ability to drive vehicles and mechanisms.Due to the possibility of an excessive decrease in blood pressure, the development of dizziness, drowsiness and other side effects at the beginning of treatment, patients should refrain from driving a car and driving other vehicles, work with mechanisms and perform other work that requires concentration.

Reporting side effects

Report side effects of the company “Arpimed” by going to the website www.arpimed.com and fill out the appropriate form “Report side effects or drug ineffectiveness” and to the Scientific Center for the Expertise of Drugs and Medical Technologies named afterAcademician E. Gabrielyan by going to the website www.pharm.am in the section “Report side effects of the drug” and fill out the form “Card of messages about side effects of the drug”. Scientific center hotline: +37410200505; +37496220505

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25 90 257 0 90 258 C in its original packaging.

Shelf life

Shelf life – 3 years.Do not use after the expiration date.

Vacation conditions

Available by prescription.

Form of issue and packaging

Cardboard package containing 40 tablets (1 blister of 40 tablets).

90,000 Arterial hypertension in hemodialysis patients receiving atenolol or lisinopril: a randomized controlled trial

A study from the United States was conducted to compare the regression of left ventricular hypertrophy during antihypertensive therapy with β-blockers and angiotensin-converting enzyme inhibitors in patients receiving an enzyme with arterial hypertension and echocardiographic signs of left ventricular hypertrophy.

Patients were randomly assigned to open-label study groups who received lisinopril (n = 100) and atenolol n = 100) 3 times a week after dialysis. Blood pressure was monitored monthly at home, so that when taking medications, the values ​​did not exceed 140/90 mm Hg, adjust the “dry weight” and limit the intake of sodium chloride. The main criterion of effectiveness: change in the left ventricular mass index (LVMI) from the initial value within 12 months.

Baseline data on blood pressure in an outpatient setting for 44 hours in the groups taking atenolol (151.5 / 87.1 mm Hg.Art.) and lisinopril were similar and improved equally over time in both groups. However, when measured monthly at home, blood pressure values ​​in the lisinopril group were significantly higher, despite taking several antihypertensive drugs and a greater decrease in dry weight in both groups. The Independent Safety Review Board recommended that the study be discontinued for cardiovascular safety reasons. Serious cardiovascular complications occurred in 16 people taking atenolol (20 complications) and 28 people taking lisinopril (43 complications) (disease rate (IRR) 2.36 (95% confidence interval [95% CI] 1.36 -4.23, p = 0.001)).Combined cardiovascular complications such as myocardial infarction, stroke and hospitalization due to heart failure or death from cardiovascular causes occurred in 10 patients taking atenolol (11 complications) and 17 patients taking lisinopril (23 complications) (IRR 2, 29, p = 0.021). In the lisinopril group, there were more hospitalizations for heart failure (IRR 3.13, p = 0.021). In the group taking lisinopril, the number of hospitalizations for all reasons exceeded that in the other group (disease incidence rate 1.61 [95% CI 1.18-2.19, p = 0.002]).Left ventricular mass index improved over time, with no difference in efficacy between the drugs.

The authors conclude that in dialysis patients with arterial hypertension and left ventricular hypertrophy, atenolol-based antihypertensive therapy is better at preventing cardiovascular complications and hospitalization for other reasons than lisinopril-based therapy. (Supported by the National Institute of Diabetes, GI and Kidney Diseases; clinical trial state number NCT00582114).

Modern possibilities of a fixed combination of an ACE inhibitor and a diuretic in the treatment of arterial hypertension

Journal “Medical Council” No. 16, 2019

DOI: https://doi.org/10.21518/2079-701X-2019-16-10-18

Gorokhovskaya G.N. ¹ , Yun V.L. ¹ , Martynov A.I. ¹ ., Vasyuk Yu.A. ¹ , Moiseenko S.V . ²

¹ Moscow State University of Medicine and Dentistry named after A.I. Evdokimova; ² Central Clinical Hospital with Polyclinic

Despite the advances in modern medicine, arterial hypertension (AH) still remains one of the main causes of fatal complications, such as myocardial infarction and acute cerebrovascular accident, leading to disability and death of patients, including those of working age.The prevalence of hypertension is significantly higher in elderly and senile people, however, in young and middle-aged people, it has recently acquired a tendency to increase. Thus, according to the Russian epidemiological study ESSE-RF, which studied representative samples of the Russian population aged 25-64, the prevalence of hypertension in this age group was 44%. By 2025, an increase in the number of patients with hypertension is predicted by 15-20%, thus it will amount to about 1.5 million people in the world.Due to the frequent occurrence and associated complications, the further study of pathogenetic mechanisms, the development of diagnostic methods of examination, the implementation of preventive measures and the search for new treatment options with fixed combination drugs is an urgent area of ​​modern medicine. This article analyzes a review of clinical studies of the components (lisinopril and indapamide) of a rational combination of an ACE inhibitor + a diuretic with a clinical example.

For citation: Gorokhovskaya G.N., Yun V.L., Martynov A.I., Vasyuk Yu.A., Moiseenko S.V. Modern possibilities of a fixed combination of an ACE inhibitor and a diuretic in the treatment of arterial hypertension. Medical Advice 2019; (16):

Conflict of interest: the authors declare that they have no conflicts of interest.

Current perspectives on fixed-dose ACE inhibitordiuretic combination therapy in the management of arterial hypertension

Galina N.Gorokhovskaya ¹ , Viktoriya L. Yun ¹ , Anatoliy I. Martynov ¹ , Yuriy A. Vasyuk ¹ , Svetlana V. Moiseenko ²

¹ A.I. Yevdokimov Moscow State University of Medicine and Dentistry, ² Central Clinical Hospital of the Presidential Administration of the Russian Federation; Moscow

Introduction

In the Russian Federation, arterial hypertension (AH) remains one of the most pressing medical and social problems.According to the epidemiological study of the ESSE RF, which was carried out in 9 regions in 2012-2013. and included data from 5 563 men and 9 737 women aged 25–64 years [1], the prevalence of hypertension was 44% (48.2% in men and 40.8% in women). At the same time, the number of patients who effectively control blood pressure is about 6-7%. The high significance of this disease is due not only to its widespread prevalence, but also to the fact that hypertension is the most important risk factor for major cardiovascular diseases (CVD) – myocardial infarction (MI) and cerebral stroke, which determine the high mortality rate of the working-age population [1-4].With a decrease in blood pressure by only 13/6 mm Hg. Art. the risk of developing cerebral stroke decreases by an average of 40% and the risk of MI – by 16%. Among people with hypertension, mortality is almost 2 times higher compared with people with normal blood pressure. In this connection, the strategic goal of the treatment of hypertension is to minimize the risk of developing cardiovascular complications (CVC) and death from them. To achieve this, not only a decrease in blood pressure to the target level is required, but also the correction of all modifiable risk factors (smoking, dyslipidemia, hyperglycemia, obesity), prevention, slowing down the rate of progression and / or reduction of target organ damage, as well as treatment of associated and concomitant diseases. (ischemic heart disease (IHD), diabetes mellitus (DM) and others) [5].

Thus, the urgency of studying the foundations of pathogenesis and possible ways of pharmacotherapy of this pathology is explained, which ultimately should provide an improvement in the prognosis in patients with their long-term use [6].

Choice of fixed combination of angiotensin-converting enzyme inhibitor and diuretic

The choice of the optimal therapy is not an easy task, especially given the expansion of the pharmaceutical market and the emergence of a large number of new drugs (drugs), as well as due to the increase in the prevalence of comorbid conditions, which greatly complicate the conduct of drug therapy and require special individual attention to monitoring the effectiveness. and drug safety [7].

According to current recommendations for the treatment of hypertension, 5 main classes of antihypertensive drugs (AGP) are recommended: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (angiotensin II receptor blockers – ARBs), calcium channel blockers (CCBs), diuretics and beta-adrenergic BB) [8-11]. The ability to prevent the development of CVO for them has been proven in numerous randomized clinical trials (RCTs) and is mainly due to a direct decrease in blood pressure.All of these drug classes are suitable for initiation and maintenance therapy. Imidazoline receptor agonists, alpha-blockers, and direct renin inhibitors (DIRs) can be used as additional classes of antihistamines for combination therapy [12].

Starting with the 2007 ESH / ESC recommendations, the lack of effectiveness of monotherapy with any antihypertensive drug, regardless of its class, is emphasized, especially in patients with hypertension of the 2nd and 3rd degree. In this connection, at the start of treatment for most hypertensive patients, low-dose combination therapy can be successfully prescribed, which is invariably more effective in lowering blood pressure than monotherapy, even low-dose combination therapy is usually more effective than monotherapy at the maximum dose [13].In addition, the combination of drugs aimed at several mechanisms of increasing blood pressure, such as blocking the renin-angiotensin-aldosterone system (RAAS), vasoconstriction, stimulation of diuresis, allows you to suppress the counter-regulatory mechanisms of increasing blood pressure [14]. A meta-analysis of more than 40 studies [15] showed that the combination of two drugs from any 2 classes of antihypertensive drugs increases the degree of blood pressure reduction much more than increasing the dose of 1 drug. Finally, combinations of the two drugs have been shown to be safe and well tolerated as initial therapy, without any risk of episodes of hypotension, even when given to patients with grade 1 hypertension [16].Adverse events leading to treatment discontinuation are infrequent in this category of patients [17]. The combination of two antihistamines in fixed doses in one tablet is recommended for all patients with hypertension, since a decrease in the number of pills taken daily improves adherence to treatment [12].

One of the rational combinations of antihistamines for the treatment of patients with hypertension is a combination therapy with an ACE inhibitor + a diuretic. Possessing a diuretic and vasodilating effect, diuretics promote the activation of the RAAS, the antihypertensive effect of an ACE inhibitor is realized by reducing the formation of angiotensin II.The combination of an ACE inhibitor + a diuretic due to the potentiation of the antihypertensive effect can significantly increase the number of patients “responding” to therapy, incl. with normo- and low-root forms of hypertension. Combined therapy with an ACE inhibitor + a diuretic prevents possible hypokalemia that develops during monotherapy with a diuretic. ACE inhibitors have a neutral effect on lipid, carbohydrate, and purine metabolism, which weakens the adverse effect of a diuretic on them [18].

Currently, there are a large number of fixed drug combinations, and of course they have a number of advantages over arbitrary combination therapy with two or more antihistamines [19]: ease of administration and dose titration process, increasing patient adherence to treatment; potentiation of the antihypertensive effect of the drugs included in this combination tablet; an increase in the percentage of patients “responding” to the appointment of a dosage form due to the multidirectional antihypertensive effect of its constituent components; reducing the frequency of side effects due to a small dose of the drugs included in the tablet, their mutual neutralization; reduction in the cost of treatment, i.e.because the price of combination drugs is less than the cost of the individual components.

Analyzing each of these components (ACE inhibitors, diuretics), it is necessary to evaluate the evidence base based on RCTs.

One of the most common and frequently prescribed ACE inhibitors is lisinopril. The advantages of lisinopril over other ACE inhibitors are that it is an initially active dosage form with a long period of action and practically does not bind to blood proteins.The absence of biotransformation in the liver allows effective and safe use of lisinopril in patients with various dysfunctions of this organ [20]. It is excreted by the kidneys unchanged. The half-life is 12 hours. Its effectiveness and safety is not influenced by the simultaneous administration of other drugs, including anticoagulants, cardiac glycosides, antiarrhythmics.

The effect of the drug manifests itself in about 60 minutes, increases for 6-7 hours and continues throughout the day, which provides a convenient prescription regimen – once a day [21].

Unlike most other ACE inhibitors, lisinopril does not contain a sulfhydryl group, which is the cause of a number of side effects (neutropenia and proteinuria) [22].

Lisinopril dilates mainly arterioles, leading to a decrease in total peripheral vascular resistance (OPSS) and a decrease in blood pressure. The ability to reduce venous tone leads to a decrease in venous return of blood to the heart and a reflex decrease in cardiac output. A decrease in the concentration of angiotensin II naturally decreases the production of aldosterone, which contributes to an increase in urine output and a decrease in circulating blood volume (BCC) [23].

Numerous clinical and experimental studies have shown that ACE inhibitors, including lisinopril, not only effectively reduce and control blood pressure, but also have a beneficial effect on the state of target organs in hypertension – myocardium, blood vessels, kidneys (suppressing the activity of both plasma and tissue links of the RAAS, ACE inhibitors can prevent and even cause the reverse development of changes occurring in target organs in hypertension). The state of target organs in hypertension has an important prognostic value and determines the tactics of managing patients with hypertension.The presence of signs of target organ damage determines the patients’ belonging to the high-risk group, the incidence of CVC in which is 20-30% over the next 10 years [12].

The earliest echocardiographic sign of the formation of a hypertensive heart is a violation of the diastolic function of the left ventricular myocardium. Under the action of angiotensin II and aldosterone, the synthetic function of fibroblasts increases, which leads to the accumulation of collagen fibers in the myocardium, an increase in its rigidity and a decrease in the compliance of the heart walls.Subsequently, there is an increase in the mass of the left ventricular myocardium. The development of myocardial hypertrophy in hypertensive patients has an unfavorable prognostic value, since it is associated with a 2–6-fold increase in the risk of CV development [24]. In addition, further progression of hypotrophic and fibrotic changes in the myocardium can lead to a decrease in myocardial contractility and the development of systolic heart failure. Data were obtained indicating regression of left ventricular myocardial hypertrophy during treatment with lisinopril, as well as improved endothelial function.The mechanism of regression of left ventricular myocardial hypertrophy when using lisinopril is due to both hemodynamic and metabolic effects of the drug: inhibition of the formation of angiotensin, which has a negative effect on pressure in the left ventricle and coronary blood flow, and prevention of the breakdown of bradykinin, which, on the contrary, increases pressure in the left ventricle, promotes increased coronary blood flow and myocardial contractility. Thus, against the background of long-term therapy with ACE inhibitors, in particular lisinopril, there is a reverse development of myocardial hypertrophy and an improvement in the functional state of the left ventricle [25].

The largest study examining the effectiveness of lisinopril in patients with hypertension was the ALLHAT (The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study. This study compared the effects of four different drug groups on hypertension outcomes: diuretics (chlorthalidone), ACE inhibitors (lisinopril), calcium antagonists (amlodipine), and alpha-blockers (doxazosin). Lisinopril was prescribed in doses of 10-40 mg / day. In this study, which involved 15,255 hypertensive patients, there was no difference between a diuretic, an ACE inhibitor, and a calcium antagonist in terms of the effect on the primary endpoint – fatal coronary heart disease and nonfatal MI.It was also concluded that blood pressure with the used drug lisinopril can be controlled in 2/3 of patients, and that in order to achieve target blood pressure values ​​(less than 140/90 mm Hg), as a rule, it is necessary to use a combination of drugs. The most interesting results of this study include data on a decrease in the risk of developing new cases of diabetes mellitus (DM) in patients who received lisinopril, compared with patients who received chlorthalidone. The incidence of new cases of diabetes detected after 2 years of treatment was almost twice as high in patients treated with chlorthalidone compared with patients treated with lisinopril.The same trend persisted after 4 years from the start of treatment. In patients taking lisinopril, the blood glucose level was lower. These differences reached significance after 2 years and remained significant until its end [26].

In a study by G. S. Stergiou and co-authors with 32 patients who received 80 mg of telmisartan or 20 mg of lisinopril, results were obtained that did not differ in blood pressure values ​​both in office measurements and in the data of daily blood pressure monitoring.Thus, in this comparative clinical study, it was revealed that the antihypertensive activity of lisinopril is not inferior to the effectiveness of telmisartan, one of the most common representatives of angiotensin II receptor blockers [27].

In the studies of M. Diamant and K. Landmark et al, a direct comparison of the antihypertensive efficacy of enalapril and lisinopril was carried out, according to the results of which the superiority of lisinopril was proved with comparable tolerability of both drugs [23].

In a Norwegian multicenter study, the hypotensive efficacy, tolerance and effect of lisinopril (mean dose 18.8 mg) and nifedipine (mean dose 37.4 mg) on ​​quality of life were studied in 828 patients with mild to moderate hypertension. Lisinopril was more effective in lowering blood pressure, better tolerated by patients. Both drugs had an equally good effect on the quality of life of patients [26].

In a multicenter, double-blind, randomized, placebo-controlled study TROPHY, a comparative study of the effectiveness of 12-week therapy of 232 obese patients with hypertension with lisinopril and hydrochlorothiazide (HCT) was carried out.The ABPM data showed that lisinopril and HCT effectively reduced blood pressure throughout the day compared with placebo (p <0.001). However, a decrease in DBP below 90 mm Hg. observed in 60% of patients treated with lisinopril, and only in 43% of patients treated with hydrochlorothiazide (p <0.05). It is important that the majority of patients (57%) who took lisinopril remained at a dose of 10 mg during the entire treatment period, while the majority of patients receiving HCT (71%) needed an increase in the dose to 25–50 mg per day. , which is associated with extremely unfavorable metabolic effects.Both drugs did not significantly affect insulin levels and lipid profiles, but plasma glucose levels after 12 weeks differed significantly (p <0.001) between the lisinopril (–0.21 mmol / L) and hydrochlorothiazide (+0.31 mmol / L) groups [22].

The two-year study ELVERA (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 hypertension who did not receive antihypertensive therapy.The study included 166 hypertensive patients (DBP 95-115 mm Hg and SBP 160-220 mm Hg) aged 60 to 75 years: 81 patients received amlodipine at a dose of 2-10 mg / day, 85 patients received lisinopril at a dose of 10–20 mg / day. The left ventricular myocardial mass index (LVMI) decreased by 25.7 g / m ² in the amlodipine group and by 27 g / m ² in the lisinopril group [28].

The SAMPLE study involved 206 patients with hypertension and left ventricular hypertrophy. Against the background of lisinopril therapy at a dose of 20 mg / day in combination with HCT (12.5–25 mg / day) and without it, an adequate decrease in blood pressure and a decrease in LVMI by 15.8% were observed [22].

Thus, ACE inhibitors play an important role among antihypertensive drugs, however, according to the available evidence-based medicine base, other classes of antihypertensive drugs, including the class of diuretics, are not inferior in effectiveness and are equivalent in terms of and influence on the prognosis of hypertension.

Of all the classes of drugs used in the long-term treatment of hypertension, diuretics are one of the longest used. Potentiating the effect of other drug groups, they are an integral part of combined antihypertensive therapy, the effect of which can be manifested at the initial stages of treatment of patients with hypertension.In the European and American cardiac guidelines, thiazide-like diuretics are also recommended for use in the treatment of hypertension in a combination therapy regimen [29].

One of the worthy representatives of the new generation of thiazide-like diuretics is indapamide, which has a clinical history as an effective antihypertensive drug with good tolerance. Its short-term effect is mediated by the effect on the proximal part of the distal tubules of the nephron, which causes the presence of a natriuretic effect characteristic of representatives of the class of diuretics.However, this representative of the family of diuretics also has additional antihypertensive activity, which is manifested primarily by a vasodilating effect [31].

The antihypertensive effect of indapamide was compared in a multicenter, double-blind, randomized study with the effect of amlodipine (5 mg / day) and HCT (25 mg / day). The study included 605 hypertensive patients (mean age 72.4 years) who received therapy for 3 months. As a result of the study, there was a decrease in blood pressure in all treatment groups, the number of patients who responded to monotherapy was higher in the group using indapamide (75.3%) in comparison with the groups where amlodipine (66.9%) and HCT (67.3%) were used. %).In the subgroup of patients with isolated systolic hypertension, a similar trend was observed: the number of responders to therapy with indapamide was 84.2%, amlodipine – 80%, and HCT – 71.4% [31].

In a multicenter study LIVE (Left ventricle hypertrophy: Indapamide Versus Enalapril), the organoprotective properties of indapamide were shown. In this study, a comparative study of the effect of therapy with indapamide and enalapril on the regression of the mass of the left ventricular myocardium (LVMM) was carried out.The study included 505 patients (255 in the indapamide group and 250 in the enalapril group) with mild to moderate hypertension and an increase in LVMM (> 120 g / m2 in men and> 100 g / m2 in women). For 1 year, patients were prescribed indapamide retard 1.5 mg / day or enalapril at a dose of 20 mg / day in one dose. As a result, it was shown that treatment with indapamide retard led to a significant decrease in LVMM (p <0.001) when compared with the results of treatment with enalapril. Indapamide retard also led to a greater degree of regression of left ventricular hypertrophy compared with enalapril (p <0.049) [32].

During the NESTOR study, the nephroprotective effect of indapamide was proven. In 570 included patients with hypertension and type 2 diabetes mellitus, a comparative study of the effect of indapamide retard (1.5 mg) and enalapril (10 mg) on ​​the severity of microalbuminuria was carried out during the year. As a result of the study, there were no differences in the severity of the antihypertensive effect, but there was a decrease in the rate of albumin secretion in the enalapril group by 37%, and in the indapamide retard group by 45%.The nephroprotective effect of indapamide retard (1.5 mg) was comparable to that of enalapril [30].

Thus, to date, a large evidence base has been accumulated in the world to study the efficacy, tolerability, benefits in terms of the effect on the state of target organs and indicators of cardiovascular risk of ACE inhibitors and diuretics, as strong antihypertensive drugs.

However, in the treatment of patients with hypertension, both at the initial stages of the disease and at the stage of progressive damage to target organs, it is often necessary to use fixed combinations of drugs in order to achieve additional effects.

One of the new combined drugs is a fixed combination of an ACE inhibitor (lisinopril 5 mg) and a diuretic (indapamide 1.5 mg). Each of these drugs has a large evidence base and is widely used in clinical practice in the treatment of patients with hypertension.

Both components have the properties of peripheral vasodilators, enhance the antihypertensive effects of each other, while they differ in metabolic neutrality, do not cause disorders of carbohydrate and lipid metabolism, which is especially important given the high prevalence of metabolic disorders in the population of patients with hypertension [23].

Thus, while retaining all the advantages of individual monocomponents that are familiar to doctors and patients, which are part of a fixed combination, the drug opens up new modern possibilities of fixed combinations in the treatment of hypertension.

Clinical case

Patient M., 56 years old, was admitted to the cardiology department of City Clinical Hospital N with complaints of dizziness, headaches, tinnitus, discomfort behind the breastbone, shortness of breath during exercise.

Anamnesis morbi

According to the patient, he has been suffering from hypertension for a long time (about 10 years). The maximum pressure is 200/110 mm Hg. Art. with adapted 140/90 mm Hg. Art. She took drug therapy irregularly (aspirin, egilok, enalapril), if necessary, due to an increase in blood pressure against a background of worsening health. About a year ago, she began to notice the appearance of pain behind the sternum of a aching nature, discomfort behind the sternum with moderate physical exertion, which was stopped at rest.

About 2 years ago, due to headaches and dizziness, she was hospitalized at City Clinical Hospital N, where CVD was diagnosed.

The present deterioration of the condition is noted for about a month, when, along with the destabilization of blood pressure, the above complaints intensified.

The patient was hospitalized routinely for the selection of antihypertensive therapy.

Anamnesis vitae

Born in Moscow 11.10.1963. She is married and has three children. Children were born on time, full-term, childbirth without features. Menarche at the age of 14, then menstruation took place regularly, without complications. Menopause without complications. Menopause from 55 years of age was uneventful.

Work: accountant, no harm, retired from 55 years.

Food: irregular, unbalanced.

Bad habits : alcohol abuse on holidays.

Past diseases: In 2017, hospitalization at City Clinical Hospital N, where CVD, chronic cerebral ischemia was diagnosed.

Denies allergies to drugs, denies seasonal allergies.

Heredity: Mother suffered from hypertension, died at the age of 83 from myocardial infarction. The father died of ischemic stroke at the age of 49.

Status praesens

General examination: Consciousness is clear.A condition of moderate severity. Active position.

The skin and visible mucous membranes are pink, the skin is dry. There is a pasty shins and feet.

The thyroid gland is not enlarged.

Lymph nodes: cervical, supraclavicular, submandibular, axillary, inguinal lymph nodes are not enlarged, painless on palpation.

The calf muscles are painless, the veins are not dilated.

The bones are painless when tapping, the joints are not changed.

Body temperature 36.6 ^o C.

Height 165 cm, weight 110 kg, BMI = 40.4. Abdominal circumference 121 cm.

Respiratory system : Chest of the correct form, NPV 16 per min. The rhythm of breathing is correct.

Clear pulmonary percussion sound over the entire surface of the lungs. Auscultatory vesicular breathing over the entire surface of the lungs. Wheezing is not heard.

The cardiovascular system

The cervical veins are not changed.The apical impulse is palpable in the VI intercostal space along the midclavicular line, enhanced, not diffuse.

Borders of relative cardiac dullness:

right – VI intercostal space along the right edge of the sternum,

left – III intercostal space along the midclavicular line,

upper – III intercostal space.

Auscultation of the heart: 1st and 2nd sounds are muffled.

The rhythm is correct, 88 beats / min, pulse of moderate filling of moderate tension,

BP 160/100 mm Hg.Art.

Digestive system

The tongue is moist, not coated.

The abdomen is enlarged due to subcutaneous fat, painless on palpation, participates in the act of breathing.

The liver on palpation is soft, painless, the lower edge of the liver does not protrude from under the costal arch. The gallbladder is not palpable, Ortner’s symptom is negative.

urinary system

The kidneys are not palpable, Pasternatsky’s symptom is negative.Urination is painless, regular.

Mental health and sensory organs

Consciousness is clear . Contact. Hearing and vision are preserved. Paralysis, paresis are absent. Sensitivity is normal.

Data of laboratory, instrumental research methods and specialist consultations (conclusions):

Complete blood count is within normal limits.

General urine analysis within normal limits.

ECG: Signs of left ventricular hypertrophy with impaired depolarization (ST segment in V5-V6).

Echo-KG : Consolidation of the walls of the aorta, the cusps of the aortic, mitral valves. Left ventricular hypertrophy. The cavities of the heart are not expanded. LV contractility is satisfactory. Violation of LV diastolic function. Insufficiency of the mitral valve 1 tbsp. Insufficiency of the tricuspid valve 1 tbsp. The type of LV geometry corresponds to concentric hypertrophy.EF = 46.0%.

Biochemical blood test: An increase in LDH, ALT, ALP is a consequence of the patient’s abuse of alcohol on the eve of hospitalization.

Elevated cholesterol levels are indicative of dyslipidemia and require further research.

Biochemical blood test (lipid spectrum): Type IIb dyslipidemia (increased cholesterol and triglyceride levels) was revealed.

Endocrinologist’s consultation: Obesity III degree of alimentary-constitutional genesis, stable course.

Ophthalmologist’s consultation : Hypertensive sclerotic retinal angiopathy. Moderate hyperopia

Clinical diagnosis of the underlying disease: Hypertension stage III, stage 3, IV risk of CVC.

Ischemic heart disease, angina pectoris II FC.

Complication: Insufficiency of blood circulation I st. (HSN II FC)

Diagnosis of a concomitant disease

Obesity of the III degree of alimentary-constitutional genesis.

Dyslipidemia IIb.

Cerebrovascular disease, chronic cerebral ischemia.

Risk factors: IHD, prolonged arterial hypertension, dyslipidemia with an atherogenic index of 7.0, old age.

The patient underwent hypotensive (lisinopril 5 mg + indapamide 1.5 mg once a day), cardioprotective (bisoprolol 5 mg 1 tablet once a day), antiplatelet (acetylsalicylic acid 100 mg 1 tablet once a day), metabolic with antihypoxic , angioprotective action (solution of meldonium 10% – 5 ml i.v., 10 ml once a day), nootropic (solution of piracetam 20% – 10 ml i.v., 10 ml once a day), hypolipidemic ( simvastatin 5 mg 1 tablet once a day), against the background of which there was a positive trend: health improved, exercise tolerance increased, headaches, dizziness, “tinnitus”, attacks of shortness of breath, discomfort in the precordial region ceased to bother.The pastiness of the lower extremities disappeared. The blood pressure level has reached the target figures.

Forecast : with regard to recovery – unfavorable, in view of the fact that the disease is incurable and has a chronic progressive course. With regard to working capacity – the working capacity is temporarily lost. With regard to life, it is doubtful, since it is impossible to exclude the possibility of developing life-threatening complications (it is included in the group of high risk of cardiovascular events), in connection with which, for the purpose of primary and secondary prevention of CVD, it is recommended to follow a diet, refuse alcoholic beverages, control routinely biochemical blood test, lipid spectrum, daily, while measuring blood pressure, continue taking antihypertensive, antiplatelet, cardioprotective therapy, be monitored by a cardiologist at the place of residence.

During the entire treatment, while taking the fixed combination, the patient had no episodes of CVC and side effects of the drug.

Thus, individually tailored treatment, taking into account all the features of the patient’s clinical profile and the possibilities of modern pharmacological drugs and their combinations, allows achieving the main goal – reducing the risk of CVD due to maintaining blood pressure at the target level, reverse remodeling of target organs and a positive effect on other risk factors (lipid spectrum) [33].

Conclusion

The advantages of fixed combinations include their ability to simultaneously affect different links in the pathogenesis of hypertension, as a result of which it becomes possible to achieve a more pronounced hypotensive effect in comparison with the use of monotherapy drugs that are part of the combined drug, especially in cases where one of them is sufficiently complete blocks the activation of counter-regulatory mechanisms due to the action of another component.In this case, the need to use high doses of individual drugs often disappears [34].

In addition to the latter, an important advantage of the use of fixed-dose combined antihypertensive drugs is an improvement in patient compliance with the prescribed therapy regimen, thereby increasing patient adherence to treatment, and consequently, the likelihood of a favorable outcome of the disease.

The high efficacy of lisinopril and indapamide, proven in a number of large RCTs, allows the combination of these drugs to be considered the optimal clinical choice in the treatment of patients with hypertension and diabetes mellitus, chronic heart failure, previous MI, chronic renal failure and gives rise to wider use in patients with high cardiovascular risk. and concomitant pathology.

Literature / References

1. Boytsov S.A., Balanova Yu.A., Shalnova S.A., Deev A.D., Artamonova G.V., Gatagonova T.M., Duplyakov D.V., Efanov A.Yu., Zhernakova Yu.V., Konradi A.O., Libis R.A., Minakov A.V., Nedogoda S.V., Oshchepkova E.V., Romanchuk S.A., Rotar O. P., Trubacheva I .A., Chazova I.E., Shlyakhto E.V., Muromtseva G.A., Evstifeeva S.E., Kapustina A.V., Konstantinov V.V., Oganov R.G., Mamedov M.N. ., Baranova E.I., Nazarova O. A., Shutemova O. A., Furmenko G. I., Babenko N. I., Azarin O. G., Bondartsov L. V., Khvostikova A. E., Ledyaeva A. A., Chumachek E. V., Isaeva E. N., Basyrova I. R., Kondratenko V. Yu., Lopina E. A., Safonova D. V., Skripchenko A. E., Indukaeva E. V., Cherkass N. V., Maksimov S.A., Danilchenko Ya.V., Mulerova T.A., Shalaev S.V., Medvedeva I.V., Shava V.P., Storozhok M.A., Tolparov G.V. , Astakhova ZT, Toguzova ZA, Kaveshnikov VS, Karpov RS, Serebryakova VN Arterial hypertension among people aged 25–64 years: prevalence, awareness, treatment and control.Based on research materials ESSE. Cardiovascular therapy and prevention. 2014; 13 (4): 4-14. doi: 10.15829 / 1728-8800-2014-4-4-14.
2. Klimov A.V., Denisov E.N., Ivanova O.V. Arterial hypertension and its prevalence among the population. Young scientist. 2018; 50 (236): 86-90. Access mode: https://moluch.ru/archive/236/54737/
3. Drapkina O.M. Isolated systolic hypertension is the lot of elderly hypertensive patients. Difficult patient. 2012; 10 (12): 10-13. Access mode: http: // t-pacient.ru / articles / 197/
4. Parfenov V.A., Ostroumova T.M., Ostroumova O.D. Arterial hypertension and dizziness: is there a relationship? Rational pharmacotherapy in cardiology. 2019; 15 (1): 125-129. doi: 10.20996 / 1819-6446-2019-15-1-125-129.
5. E.P. Panchenko, Yu.N. Belenkov Characteristics and outcomes of atherothrombosis in outpatients in the Russian Federation (based on the materials of the international register REACH). Cardiology. 2008; (2): 17-24. doi: 10.20996 / 1819-6446-2013-9-5-494-499.
6. Karpov Yu.A. Angiotensin-converting enzyme inhibitors in mono- and combined therapy of arterial hypertension. Breast cancer. 2009; 17 (18): 1122-1126. Access mode: https://www.rmj.ru/articles/kardiologiya/Ingibitory_angiotenzinprevraschayuschego__fermenta_v_mono_i
7. Yudina I.Yu., Morozova T.E. Clinical use of fixed combinations of antihypertensive drugs. Therapist. 2015; (2): 8. Access mode: https://www.lvrach.ru/2015/02/15436155/
8. Brunstrom M., Carlberg B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA Internal Medicine. 2018; 178: 28–36. doi: 10.1001 / jamainternmed.2017.6015.
9. Ettehad D., Emdin CA, Kiran A., Anderson SG, Callender T., Emberson J., Chalmers J., Rodgers A., Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta -analysis. Lancet. 2016; 387: 957-967.doi: 10.1016 / S0140-6736 (15) 01225-8.
10. Thomopoulos C., Parati G., Zanchetti A. Effects of blood pressure-lowering on outcome incidence in hypertension: Head-to-head comparisons of various classes of antihypertensive drugs – overview and meta-analyzes. Journal of Hypertension. 2015; 33: 1321-1341. doi: 10.1097 / HJH.0000000000000447.
11. Rutten F.H., Zuithoff N.P., Halk F., Grobbee D.E., Hoes A.W. Beta-Blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease.Archives of Internal Medicine. 2010; 170: 880–887. doi: 10.1001 / archinternmed.2010.112
12. Chazova I.E. Clinical guidelines. Diagnostics and treatment of arterial hypertension. Systemic hypertension. 2019; 16 (1): 6-31. doi: 10.26442 / 2075082X.2019.1.1

    .

13. Wald D.S., Law M., Morris J.K., Bestwick J.P., Wald N.J. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. American Journal of Medicine. 2009; 122: 290-300.doi: 10.1016 / j.amjmed.2008.09.038.
14. MacDonald TM, Williams B., Webb DJ, Morant S., Caulfield M., Cruickshank JK, Ford I., Sever P., Mackenzie IS, Padmanabhan S., McCann GP, ​​Salsbury J., McInnes G. Combination therapy is superior to sequential monotherapy for the initial treatment of hypertension: a double-blind randomized controlled trial. Journal of the American Heart Association. 2017; 6: e006986. doi: 10.1161 / JAHA.117.006986.
15. Thomopoulos C., Parati G., Zanchetti A .. Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyzes of randomized trials. Journal of Hypertension. 2016; 34: 1921-1932. doi: 10.1097 / HJH.0000000000001052.
16. Yusuf S., Lonn E., Pais P., Bosch J., López-Jaramillo P., Zhu J., Xavier D., Avezum A., Leiter LA, Piegas LS, Parkhomenko A., Keltai M., Keltai K., Sliwa K., Chazova I., Peters RJ, Held C., Yusoff K., Lewis BS, Jansky P., Khunti K., Toff WD, Reid CM, Varigos. J, Accini JL, McKelvie R., Pogue J., Jung H., Liu L., Diaz R., Dans A., Dagenais G. HOPE-3 Investigators. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. New England Journal of Medicine. 2016; 374: 2032–2043. doi: 10.1056 / NEJMoa1600177.
17. Corrao G., Zambon A., Parodi A., Poluzzi E., Baldi I., Merlino L., Cesana G., Mancia G. Discontinuation of and changes in drug therapy for hypertension among newly-treated patients: a population- based study in Italy.Journal of Hypertens. 2008; 26: 819-824. doi: 10.1097 / HJH.0b013e3282f4edd7.
18. Britov A.N. Angiotensin-converting enzyme inhibitors in the treatment and prevention of arterial hypertension and metabolic syndrome, the place of lisinopril. Difficult patient. 2009; 7 (10): 35-39. Access mode: http://t-pacient.ru/articles/6482/
19. Chazova I.E. Arterial hypertension in the light of current recommendations. Therapeutic archive. 2018; 90 (9): 4-7. doi: 10.26442 / terarkh30189094-7.
20. Minushkina L.O. Lisinopril in the treatment of arterial hypertension in patients with concomitant liver pathology. Pharmateca. 2010; (5): 39-44. Access mode: https://pharmateca.ru/ru/archive/article/7768.
21. Podzolkov V.I., Osadchiy K.K. ACE inhibitors in the treatment of hypertension: a focus on lisinopril. Rational pharmacotherapy in cardiology. 2009; 5 (1): 57-62. doi: 10.20996 / 1819-6446-2009-5-1-57-62.
22. Volkov A.V. Lisinopril: a universal drug in the arsenal of a cardiologist. Breast cancer.2010; 18 (3): 145-148. Access mode: https://www.rmj.ru/articles/kardiologiya/Lizinopril_universalynyy_preparat__v_arsenale_vracha_kardio
23. Podzolkov V.I., Dragomiretskaya N.A. The use of a fixed combination of lisinopril and indapamide for optimal cardioprotection in hypertensive patients. Arterial hypertension. 2018; 24 (4): 459-468. doi: 10.18705 / 1607-419X-2018-24-4-459-468.
24. Barsukov A.V., Glukhovskoy D.V., Talantseva M.S., Bagaeva Z.V., Pronina E.V., Zobnina M.P., Sveklina T.S., Korovin A.E. Left ventricular hypertrophy and the renin-angiotensin-aldosterone system: AT1-angiotensin receptor blockers in focus. Systemic hypertension. 2013; (1): 88-96. Access mode: https://con-med.ru/magazines/hypertension/hypertension-01-2013/gipertrofiya_levogo_zheludochka_i_ren
25. Evdokimova A.G., Evdokimov V.V., Smetanin A.V., Yunko S.A. Arterial hypertension and high risk of cardiovascular complications: focus on lisinopril. Difficult patient.2010; 8 (11): 9-13. Access mode: http://t-pacient.ru/articles/6598/
26. Jaiani N.A. Some aspects of the use of lisinopril in arterial hypertension. Rational pharmacotherapy in cardiology. 2010; 6 (1): 95-102. doi: 10.20996 / 1819-6446-2010-6-1-95-102.
27. Baryshnikova G.A., Stepanova I.I., Chuprova N.V. The role of angiotensin-converting enzyme inhibitors in the treatment of hypertension: a focus on lisinopril. Therapist. 2013; (2): 13. Access mode: https: // www.lvrach.ru/2013/02/15435617/
28. Podzolkov V.I., Tarzimanova A.I. The value of lisinopril in clinical practice. Rational pharmacotherapy in cardiology. 2010; 6 (4): 565-568. doi: 10.20996 / 1819-6446-2010-6-4-21-25.
29. Williams B., Mancia G., Spiering W., Agabiti Rosei E., Azizi M., Burnier M., Clement DL, Coca A., de Simone G., Dominiczak A., Kahan T., Mahfoud F., Redon J., Ruilope L., Zanchetti A., Kerins M., Kjeldsen SE, Kreutz R., Laurent S., Lip GYH, McManus R., Narkiewicz K., Ruschitzka F., Schmieder R. E., Shlyakhto E., Tsioufis C., Aboyans V., Desormais I .; ESC Scientific Document Group. 2018 ESC / ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European Heart Journal. 2018; 39 (33): 3021-3104. doi: 10.1093 / eurheartj / ehy339.
30. Zagidullin N.Sh., Almukhametova G.M., Safina Yu.F., Nigmatullina K.F., Rakhmatullina V.T., Konovalov V.N., Rezbaeva A.G., Zagidullin Sh.Z. On the optimization of arterial hypertension therapy: a combination of an angiotensin-converting enzyme inhibitor and a diuretic. Outpatient doctor’s reference book. 2013; (11): 27-31. Access mode: https://con-med.ru/magazines/physician/physician-11-2013/k_voprosu_ob_optimizatsii_terapii_arterialn
31. Chukaeva I.I., Spiryakina Ya.G. Indapamide retard drug of choice in elderly patients with arterial hypertension. Russian journal of cardiology.2013; 18 (5): 56-60. doi: 10.15829 / 1560-4071-2013-5-56-60.
32. Ostroumova O.D., Dudaev V.A. Diuretics in the treatment of arterial hypertension: focus on long-acting indapamide. Outpatient doctor’s reference book. 2010; (10): 37-40. Access mode: https://con-med.ru/magazines/physician/physician-10-2010/diuretiki_v_lechenii_arterialnoy_gipertonii
33. Alekhina O.D., Burlachuk V.T. Clinical example: management of a patient with essential hypertension on an outpatient basis.Outpatient doctor’s reference book. 2013; (3): 18-20. Access mode: http://t-pacient.ru/articles/160/
34. Yudina I.Yu., Morozova T.E. Clinical use of fixed combinations of antihypertensive drugs. Therapist. 2015; (2): 8. Access mode: https://www.lvrach.ru/2015/02/15436155/

Relief of hypertensive crisis in Yekaterinburg

Hypertensive crisis (HA) is a sharp increase in blood pressure (BP) , accompanied by symptoms.A crisis is a life-threatening condition. Requires immediate action to lower blood pressure. A crisis should be distinguished from a simple short-term increase in blood pressure, which is asymptomatic and does not pose a threat to life.

The main reasons for the development of a hypertensive crisis:

• lack of drug therapy GB, SAG
• Cancellation of drugs prescribed to lower blood pressure
• acute respiratory viral disease
• exacerbation of any concomitant pathology (bronchial asthma, diabetes mellitus, stomach ulcer, etc.)etc.)
• pain syndrome of any localization, especially of the musculoskeletal system (spine, joints)
• physiotherapy for any pathology, especially the musculoskeletal system
• taking painkillers, anti-inflammatory drugs (nise, diclofenac, celecoxib, etc.)
• injuries (especially craniocerebral)
• bleeding, severe blood loss
• surgical interventions (especially abdominal, i.e.i.e. carried out on the organs of the chest; abdominal cavity)
• alcohol abuse, especially strong alcoholic beverages in significant quantities
• coffee, strong tea in significant quantities
• heavy smoking
• drugs
• sleep disturbance, work without holidays, days off, especially in chronic mode
• night shift work
• Frequent flights, transfers
• strong psycho-emotional shocks
• increased salt content in food
• a combination of several factors (for example, pain in the spine, taking anti-inflammatory drugs, physiotherapy)

Main mechanisms of development of HA and SAG:

• increased release of adrenaline, adrenal hormones, leading to increased heart rate, increased vascular tone (spasm).More often this type of crises develops in men.
• Increased retention of salts and water in tissues, leading to edema of the vascular wall. This type of hypertension is more typical for women, they are more prone to fluid accumulation.

The main symptoms of a hypertensive crisis are those that reflect an increased load on the following organ systems:

• Central and peripheral nervous system:
• headache
• nausea
• vomiting
• visual impairment, hearing impairment
• photophobia
• convulsions
• loss of consciousness
• speech disorders, coordination
• numbness of a part of the face, tongue, part of the body, limbs (sided)
• paralysis of a part of the body, limbs (loss of motor function, side effects are also characteristic)
• feeling hot or chilly
• increased sweating
• fear of death

Cardiovascular system:

• arrhythmias (tachycardia, atrial fibrillation, extrasystole)
• chest pain
• shortness of breath
• myocardial infarction, angina attack
• acute heart failure (pulmonary edema)
• dissecting aortic aneurysm

Urinary system:

• acute kidney injury, acute renal failure
• frequent urination

Gastrointestinal tract:

• nausea
• vomiting
• urge to defecate

The degree of increase in blood pressure does not always determine the risk of developing symptoms.A patient with hypertension and arterial hypertension has its own “limit level” of blood pressure increase, even with low blood pressure values, any of the complications may develop.

If the crisis is tolerated by the patient relatively satisfactorily, without life-threatening, painful symptoms for him, then the patient can be left at home and continue treatment on an outpatient basis. Such crises are uncomplicated.

If the crisis is subjectively poorly tolerated by the patient, with symptoms painful for him, or posing a threat to his life, then the patient is immediately admitted to the hospital.The crisis is complicated, requires a call emergency medical service (EMS) ! The most frequent, life-threatening complications of such crises: pulmonary edema, an attack of angina pectoris or myocardial infarction, cardiac arrhythmias (atrial fibrillation), etc.

When complicated, a hypertensive crisis with repeated development may again be accompanied by the development of life-threatening conditions. In case of repeated development of HA in such patients, it is necessary to induce an EMS, WITHOUT WAITING FOR COMPLICATIONS!

Basic rules for the relief of hypertensive crisis:

• Keep Calm! The more nervous the patient himself, his relatives, the less chances of a quick, successful relief of HA.This is no coincidence. With any mechanism of HA development, the release of adrenaline “does its dirty work”, vasospasm inevitably develops (that is, a sharp increase in their tone), in this case, the load on the heart increases significantly, because it has to push blood through the resistance of the vascular wall.
• Contact the patient’s healthcare professional as soon as possible. Perhaps a simple dose adjustment of planned antihypertensive therapy will help prevent the development of a crisis, or ease its course
• Place the patient on a comfortable, level surface.In the horizontal position, the risk of an excessive decrease in blood pressure is minimal and the patient is insured against injuries associated with dizziness, loss of consciousness against the background of a sharp / excessive fall in blood pressure.

Eliminate patient irritants:

• open / remove tight clothing
• to mute the radio, or TV
• turn off bright lights, curtain windows
• talk softly
• isolate the patient from excessively noisy children, pets
• Give a sedative: Corvalol or Valoserdin 30-40 drops in warm water (in warm water, i.e.since those essential oils that are part of these drops dissolve in it better)

Analyze the cause of the development of the crisis, stop the effect of the provoking factor: if HA is associated, for example, with severe pain in the spine / joints, then it is necessary first of all to anesthetize the patient (intravenous or intramuscular ketonal 100 mg). If the cause of GC was a banal overwork, the patient should be given a rest, lovers of excesses (drinking alcohol, smoking intensively, consuming salty foods in increased quantities) should immediately give up their addictions, otherwise the crisis will take a protracted course, even doctors will not be able to cope with it!

• All drugs recommended for the relief of a crisis should be taken gradually, fractionally, since an excessive decrease in blood pressure can lead to a stroke, especially in the elderly!
• You should read the instructions for use of the medicinal product recommended for the relief of the crisis.In medicine, especially emergency medicine, there is no concept of “pill / half-tablet”, there is a concept of “dose” that must be observed!
• Taking medications that urgently lower blood pressure:

A) moxonidine (fiziotens, moxarel, moxonitex) is a centrally acting drug that acts on the receptors in the brain, which are responsible for vascular tone. It is an over-the-counter analogue of clonidine.

The drug is taken sublingually (under the tongue) at a dose of 0.2 mg, while maintaining elevated blood pressure values, you can repeat the dose at a dose of 0.2 mg also under the tongue, the maximum daily dose of the drug is 0.6 mg.

Can be used for any type of blood glucose, for patients with type 1 crisis (excessive anxiety, rapid pulse, rapid “jump” in blood pressure), as well as in cases of significant (over 160/90), a sharp increase in blood pressure.

For “novice” patients who first encountered GC, as well as with a moderate increase in blood pressure (up to 160/90), moxonidine is not the drug of choice, because due to a sufficiently powerful action, it can unnecessarily reduce blood pressure.

This drug can be used at any age in patients with any concomitant pathology (bronchial asthma, chronic kidney disease, heart failure, etc.)etc.).

The main side effects of moxonidine can be severe dry mouth and slow heart rate, so patients with bradycardia should take it with caution.

B). captopril (kapoten) is the “brother” of drugs such as enalapril, lisinopril, perindopril, ramipril, etc., belonging to the group of angiotensin-converting enzyme inhibitors (ACE inhibitors). These drugs block the work of an enzyme responsible for increasing vascular tone.

Captopril is the fastest-acting drug of all.It is preferable for women, as well as for people with the second type of HA, who are prone to a slow gradual increase in blood pressure against the background of fluid and salt retention.

The drug is taken sublingually at a dose of 12.5-25 mg, while maintaining elevated blood pressure after 30 minutes, you can repeat the drug in the same dose. The maximum effective dose of the drug for lowering blood pressure is 50 mg. You do not need to exceed it, but you need to take a drug of another group (for example, moxonidine, but with a minimum dose of 0.2 mg).

May cause dry persistent cough like other members of the ACE inhibitor group.This effect is not comfortable for the patient, but does not pose a threat to his life, it passes, since the drug has a short effect.

Captopril is preferable for patients taking an antihypertensive drug for the first time, as well as with a moderate increase in blood pressure (up to 160/90), because it has a rather mild effect.

The drug does not affect the pulse, it can be used in patients with bradycardia.

It is undesirable to take it in the presence of severe kidney disease (renal failure with high creatinine values, in patients on hemodialysis).

B) anaprilin (obzidan) is a fast-acting beta-blocker. This group includes bisoprolol, metoprolol, carvedilol, but their effect occurs gradually, they are drugs for planned therapy. The main mechanism of action is to protect the body from the release of adrenaline and its effects – panic, tachycardia, anxiety.

Anaprilin (NOT ENALAPRIL – DO NOT CONFUSE THE NAME) is indicated for patients with type 1 crisis, when anxiety, panic, increased sweating, rapid pulse come to the fore.

The drug is taken under the tongue at a dose of 5-10 mg, if there is no effect after 30 minutes, you can repeat it in the same dose. The maximum effective dose for the relief of GK is 20-30 mg.

Often causes a burning sensation under the tongue, but this effect does not pose a threat to the patient’s life, it may not be taken into account by him.

Reception of anaprilin is contraindicated in bronchial asthma, chronic obstructive pulmonary disease, bradycardia, severe heart failure.

Medicines (drugs) belong to different groups of hypotensive, can be combined with each other, it is also possible to switch from one drug to another. It is necessary to start with the minimum recommended doses, since the accumulation of drugs is possible, this will lead to an excessive decrease in blood pressure.

Only your attending physician can recommend an antihypertensive drug for the relief of a hypertensive crisis individually, because the mechanisms of increasing blood pressure are different. Sometimes it is enough to contact your doctor, adjust the doses of constantly taken antihypertensive drugs, this will prevent the development of HA.

If the recommended drugs do not work, the patient cannot cope with GC – call an EMP.

However, it should be remembered that calls from the emergency medical service regarding increased blood pressure continue to lead in the list of requests, sometimes creating an unreasonably high workload on specialists.

Hypertension, symptomatic arterial hypertension is an outpatient pathology that does not require hospitalization.

Outpatient therapy, strict adherence by the patient to the recommendations of his attending physician is the only reliable means of preventing HA. It is important to be constantly monitored by one doctor who knows the course of the disease of his ward, whom he trusts.

This opportunity is provided by the MO “New Hospital”. We offer dispensary observation programs specially designed by the doctors of our clinic for patients with arterial hypertension:

91 330 Service cost 91 333

Payment methods: cash payment; payment by plastic bank cards MIR, VISA, Mastercard Worldwide

instructions for use, indications, side effects

Pharmacodynamics
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, helps to reduce 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 situations
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 excretion of salt from the body and / or reduced volume of intercellular fluid, 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, 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 stop 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 to reveal 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).
Lisinopril treatment 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 starting dose for lisinopril is 5 mg orally, then 5 mg after 24 hours, 10 mg after 48 hours, and 10 mg daily. Patients with a 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), it is necessary to discontinue therapy with Lisinopril. Treatment is recommended for 6 weeks, then it is necessary to re-evaluate the patient’s condition.Patients with symptoms of heart failure need to continue their 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.
Nutrition 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 of 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 with 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 and 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 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 developing 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 (eg, 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.
Surgery / 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.Among patients at high risk of developing hyperkalemia, there are patients with renal failure, diabetes mellitus, or who are simultaneously using potassium supplements, potassium-sparing diuretics or salt substitutes with potassium content, or patients 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 patients with darker skin color 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, possibly in patients with chronic heart failure with intolerance to aldosterone antagonists (spironolactone), who have persistent symptoms of chronic heart failure, despite the other adequate therapy.

Symptoms : arterial hypotension, circulatory shock, bradycardia, water-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.Vital organs, electrolyte and serum creatinine levels should be checked frequently.
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.

.