Lisinopril/hydrochlorothiazide: Side Effects and More

Highlights for hydrochlorothiazide-lisinopril

1. Lisinopril/hydrochlorothiazide oral tablet is available as a brand-name drug and a generic drug. Brand name: Zestoretic.
2. Lisinopril/hydrochlorothiazide only comes as a tablet you take by mouth.
3. Lisinopril/hydrochlorothiazide oral tablet is used to treat hypertension (high blood pressure).

FDA warning: Use during pregnancy

• This drug has a black box warning. This is the most serious warning from the Food and Drug Administration (FDA). A black box warning alerts doctors and patients about drug effects that may be dangerous.
• You shouldn’t take this drug during pregnancy. This drug can harm or end your pregnancy. If you become pregnant, call your doctor and stop taking this drug right away.

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Other warnings

• Allergic reaction warning: This drug can cause allergic reactions. Some of these reactions can be severe. These include head and neck swelling, trouble breathing, and severe stomach pain.
• Low blood pressure warning: This drug can cause very low blood pressure. Tell your doctor if you have signs of low blood pressure, such as dizziness or feeling like you might faint.
• Liver failure warning: This drug can rarely cause a syndrome that starts as jaundice (yellowing of your skin or the whites of your eyes) and progresses to severe liver damage. If you develop jaundice or have tests that show that your liver enzymes have increased, your doctor will tell you to stop taking this drug.

Lisinopril/hydrochlorothiazide is a prescription drug. It comes as an oral tablet.

Lisinopril/hydrochlorothiazide is available as the brand-name drug Zestoretic. It’s also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in every strength or form as the brand-name drug.

Lisinopril/hydrochlorothiazide is a combination of two drugs in a single form. It’s important to know about all the drugs in the combination because each drug may affect you in a different way.

Lisinopril/hydrochlorothiazide may be taken in combination with beta-blockers, angiotensin receptor blockers, calcium channel blockers, and diuretics to treat high blood pressure. It’s usually given when one medication isn’t enough to control your blood pressure.

How it works

Lisinopril belongs to a class of drugs called angiotensin-converting enzyme (ACE) inhibitors. Hydrochlorothiazide belongs to a class of drugs called diuretics (water pills). A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

It’s thought that hydrochlorothiazide works to remove excess salt and water from your body. This keeps your heart from working as hard to pump blood. This lowers your blood pressure.

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

Hydrochlorothiazide-lisinopril oral tablet doesn’t cause drowsiness, but it can cause other side effects.

More common side effects

The more common side effects that can occur with lisinopril/hydrochlorothiazide include:

• dizziness
• headache
• persistent cough
• fatigue
• low blood pressure, especially when you stand up after sitting or lying down

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

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Serious allergic reactions. Symptoms can include:
• swelling of your head, neck, or lips
• stomach pain
• Low blood pressure. Symptoms can include:
• dizziness
• fainting
• Liver failure. Symptoms can include:
• yellowing of your skin or the whites of your eyes
• increased liver enzymes (shown in a test your doctor will do)
• fatigue
• stomach pain
• nausea and vomiting

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

Lisinopril/hydrochlorothiazide oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

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

Barbiturates and narcotics

Taking certain barbiturates and narcotics with lisinopril/hydrochlorothiazide may increase your risk of low blood pressure when standing up after sitting or lying down. Examples of these drugs include:

• phenobarbital
• morphine
• fentanyl
• hydrocodone

Blood pressure drugs

Taking other drugs that reduce blood pressure with lisinopril/hydrochlorothiazide may cause your blood pressure to drop too low. This can cause dizziness, headache, or fatigue. Examples of these drugs include:

• angiotensin receptor blockers (ARBs), such as:
• losartan
• valsartan
• olmesartan
• candesartan
• angiotensin-converting enzyme (ACE) inhibitors, such as:
• benazepril
• captopril
• enalapril
• lisinopril
• direct renin inhibitors, such as:
• aliskiren. Don’t take aliskiren with this drug if you have diabetes or kidney problems.

In addition, lisinopril/hydrochlorothiazide interacts with other blood pressure drugs that increase your potassium levels. Your doctor may check your potassium level with blood tests. Examples of these drugs include:

• potassium-sparing diuretics, such as:
• spironolactone
• amiloride
• triamterene

Cholesterol drugs

Taking lisinopril/hydrochlorothiazide with certain drugs used to lower cholesterol levels can reduce the amount of lisinopril/hydrochlorothiazide that your body absorbs. This means that it may not work as well to treat your blood pressure.

Examples of these drugs include:

• cholestyramine
• colestipol

Corticosteroids and adrenocorticotropic hormones

Taking these drugs with lisinopril/hydrochlorothiazide may cause low levels of electrolytes.

Diabetes drugs

Taking certain diabetes drugs with lisinopril/hydrochlorothiazide may affect your blood sugar levels. If you take lisinopril/hydrochlorothiazide with one of these drugs, your doctor may change the dosage of that diabetes drug.

Examples of these drugs include:

• metformin
• glyburide
• glipizide
• insulin

Injectable gold

Taking lisinopril/hydrochlorothiazide with injectable gold may cause flushing (reddening and warming of your face), stomach problems, low blood pressure, dizziness, and a fast heart rate.

Lithium

Taking lisinopril/hydrochlorothiazide with lithium can cause lithium toxicity. This may cause confusion, increased urination, thirst, or an irregular heart rate.

Pain drugs

Taking certain pain drugs with lisinopril/hydrochlorothiazide may decrease your kidney function. This can cause swelling in your legs or problems with urination. Examples of these drugs include:

• diclofenac
• indomethacin
• ketoprofen
• ketorolac
• sulindac
• flurbiprofen

Sacubitril

You should not use lisinopril/hydrochlorothiazide within 36 hours of using sacubitril. Sacubitril is used with valsartan to treat high blood pressure and heart failure. Taking sacubitril with lisinopril/hydrochlorothiazide raises your risk of angioedema (serious swelling).

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

This drug comes with several warnings.

Allergy warning

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

• trouble breathing
• swelling of your throat or tongue
• hives
• severe stomach pain

If you develop these symptoms, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it or any angiotensin-converting enzyme inhibitors, diuretics, or sulfonamide drugs. Taking it again could be fatal (cause death).

Alcohol interaction warning

The use of drinks that contain alcohol can increase your risk of a side effect from lisinopril/hydrochlorothiazide. This side effect is low blood pressure when you stand up after sitting or lying down, which can cause dizziness. If you drink alcohol, talk to your doctor.

Warnings for people with certain health conditions

For people with diabetes: This drug can affect your blood sugar levels. Your doctor may need to change your dosage of your diabetes medications.

For people with certain heart problems: This drug may lower your blood pressure too much if you have aortic stenosis or hypertrophic cardiomyopathy.

For people with poor kidney function: This drug can further reduce your kidney function. Talk to your doctor about whether this drug is safe for you.

For people with high potassium levels: This drug may increase your potassium levels more. This is often temporary, but may lead to serious heart rate problems.

For people with a cough: This drug may cause a persistent cough or make your cough worse. This cough usually goes away when you stop taking this drug.

Warnings for other groups

For pregnant women: During the first trimester, this drug is a category C pregnancy drug. That means two things:

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

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

If you become pregnant while taking this drug, call your doctor right away.

For women who are breastfeeding: This drug may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

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

For children: This drug hasn’t been studied in children. It shouldn’t be used in children under the age of 18 years.

All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:

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

Drug forms and strengths

Generic: Lisinopril/hydrochlorothiazide

• Form: oral tablet
• Strengths:
• 10 mg lisinopril/12. 5 mg hydrochlorothiazide
• 20 mg lisinopril/12.5 mg hydrochlorothiazide
• 20 mg lisinopril/25 mg hydrochlorothiazide

Brand: Zestoretic

• Form: oral tablet
• Strengths:
• 10 mg lisinopril/12.5 mg hydrochlorothiazide
• 20 mg lisinopril/12.5 mg hydrochlorothiazide
• 20 mg lisinopril/25 mg hydrochlorothiazide

Dosage for hypertension (high blood pressure)

Adult dosage (ages 18–64 years)

• Typical starting dosage: 10–20 mg lisinopril/12.5 mg hydrochlorothiazide taken once per day.
• Dosage increases: Your doctor will increase your dosage as needed. They may increase your dosage after 2–3 weeks of treatment.

Child dosage (ages 0–17 years)

This drug hasn’t been studied in children. It shouldn’t be used in children under the age of 18 years.

Senior dosage (ages 65 years and older)

• There are no specific recommendations for senior dosing. Older adults may process drugs more slowly. A typical adult dosage may cause levels of this drug to be higher than normal in your body. If you’re a senior, you may need a lower dosage or a different dosing schedule.
• Your doctor may increase your dosage after 2–3 weeks of treatment.

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

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

If you don’t take it at all: Your blood pressure may increase. This can lead to a heart attack or a stroke.

If you stop taking it suddenly: Your blood pressure may increase.

If you don’t take it on schedule: You may still have high blood pressure. Or you may have more side effects because a consistent level of the drug isn’t in your body. This drug may stop working for you and you may need to use another blood pressure medication.

What to do if you miss a dose: If you forget to take your dose, take it as soon as you remember. If it’s just a few hours until the time for your next dose, then wait and only take one dose at that time.

Never try to catch up by taking two doses at once. This could result in dangerous side effects.

If you take too much: You may have some of the side effects of this drug. These include:

• low blood pressure
• dizziness
• fainting

If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or go to the nearest emergency room right away.

How to tell if the drug is working: Your doctor will check your blood pressure to tell if this drug is working for you. Your doctor may also ask you to check your blood pressure at home.

Keep these considerations in mind if your doctor prescribes hydrochlorothiazide-lisinopril for you.

General

• This drug can be taken with or without food.
• Take this drug at the same time each day.
• Don’t crush or cut the tablet.

Storage

• Store this drug at a temperature between 68°F and 77°F (20°C and 25°C).
• Keep this drug away from light.
• Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

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

Travel

When traveling with your medication:

• Always carry your medication with you, such as in your carry-on bag.
• Don’t worry about airport X-ray machines. They can’t harm your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled container with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Self-management

You may need to check your blood pressure at home. You should keep a log with the date, time of day, and your blood pressure readings. Bring this diary with you to your doctor appointments.

To check your blood pressure, you may need to buy a blood pressure monitor. These are available at most pharmacies.

Clinical monitoring

While you’re being treated with this drug, your doctor may check your:

• blood pressure
• kidney function
• electrolyte levels

Your diet

Your diet may affect how well your high blood pressure is controlled. Ask your doctor if you should make changes to your diet.

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

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

Mylan-Lisinopril HCTZ – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

This is a combination product containing 2 medications: lisinopril and hydrochlorothiazide. It is used to treat high blood pressure.

Lisinopril belongs to a class of medications called ACE inhibitors and helps to lower blood pressure by relaxing blood vessels and reducing the workload of the heart. Hydrochlorothiazide belongs to a class of medications called diuretics or “water pills” that help control blood pressure by getting rid of excess salt and water.

It may take up to 2 to 4 weeks to see the full benefits of the medication.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor.  Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

Mylan-Lisinopril HCTZ is no longer being manufactured for sale in Canada. For brands that may still be available, search under lisinopril – hydrochlorothiazide. This article is being kept available for reference purposes only. If you are using this medication, speak with your doctor or pharmacist for information about your treatment options.

How should I use this medication?

Lisinopril – hydrochlorothiazide is not intended to be used to start treatment of high blood pressure. Each medication should be taken as a separate tablet until the appropriate dose of each medication is determined. Once the dose of each medication (lisinopril and hydrochlorothiazide) that best controls your blood pressure has been determined, the combination tablets can be started.

The recommended dose ranges are:

• lisinopril 10 mg – hydrochlorothiazide 12.5 mg, 1 tablet once daily
• lisinopril 20 mg – hydrochlorothiazide 12.5 mg, 1 or 2 tablets once daily
• lisinopril 20 mg – hydrochlorothiazide 25 mg, 1 or 2 tablets once daily

This medication can be taken with or without food. Swallow the tablet with water. Try to take your tablet at the same time each day, preferably in the morning.

Lower doses may be used for people who take other medications that lower blood pressure or for people who have kidney disease.

Do not stop taking your tablets unless your doctor recommends it.

Many things can affect the dose of medication that a person needs, such as their body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones given here, do not change the way that you are taking the medication without consulting your doctor.

It is important that this medication be taken exactly as prescribed by your doctor. If you miss a dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take this medication if you:

• are allergic to lisinopril, hydrochlorothiazide, or any ingredients of this medication
• are allergic to other angiotensin-converting enzyme inhibitors
• are allergic to sulfa (sulfonamide) medications
• are pregnant or intend to become pregnant
• are breast-feeding
• have difficulty producing urine or are unable to urinate
• have a history of angioedema after taking any ACE inhibitors (e. g., captopril, enalapril, fosinopril, lisinopril, ramipril)
• are taking aliskiren and have congestive heart failure with low blood pressure
• have hereditary angioedema (a serious allergic reaction which causes swelling of the hands, feet, ankles, face, lips, tongue, or throat) or have angioedema with no known cause
• have diabetes, kidney disease, congestive heart failure with low blood pressure, or high levels of potassium in the blood and are taking aliskiren
• are taking sacubitril/valsartan
• are taking other angiotensin converting enzyme inhibitors or angiotensin receptor blockers and have advanced diabetes, kidney disease, congestive heart failure with low blood pressure or high levels of potassium in the blood

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal pain
• cold or flu-like symptoms (e.g., runny or stuffy nose, sore throat, headache)
• constipation
• cough
• decreased appetite
• decreased interest in sexual activity
• decreased sexual ability
• diarrhea
• dizziness
• drowsiness
• fatigue
• headache
• indigestion
• nausea
• sensitivity to the sun
• skin rash
• upset stomach
• vomiting
• weakness (loss of strength)

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• discoloured patches or lumps on the skin that change slowly over time
• dizziness when rising from a sitting or lying position, lightheadedness, or fainting (signs of low blood pressure)
• joint pain (e.g., toe pain may be a sign of gout)
• muscle cramps
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of bleeding (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• signs of kidney problems (e.g., decreased urination, nausea, vomiting, swelling of legs or hands, fatigue)
• signs of liver problems such as abdominal pain, nausea or vomiting, itching of skin, yellow eyes or skin
• signs of pancreatitis (e. g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen)
• signs of too much or too little potassium in the body
• dry mouth
• increased thirst
• irregular heartbeat
• mood or mental changes
• muscle cramps or pain
• numbness or tingling in hands, feet, or lips
• weak pulse
• weakness or heaviness of legs
• symptoms of lupus (e.g., skin rash (with or without itching), fever, or joint pain)
• swelling of hands, ankles or feet
• symptoms of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odour)
• symptoms of fast heartbeat (e.g., dizziness, lightheadedness, shortness of breath, racing heartbeat)

Stop taking the medication and seek immediate medical attention if any of the following occur:

• chest pain
• severe skin rash, including skin blistering and peeling (possibly with headache, fever, coughing, or aching before the rash begins)
• symptoms of a serious allergic reaction, including angioedema (e. g., hives; swelling of the face, mouth, hands, or feet; and difficulty breathing)
• symptoms of increased pressure in the eyes or other eye problems (e.g., blind spots, decreased or blurred vision, eye pain, sudden near sightedness, red eye, swelling of the eye)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin taking a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should take this medication.

Allergic reaction: Some people who are allergic to sulfonamide medications also experience allergic reactions to hydrochlorothiazide. Before you take this medication, inform your doctor about any previous adverse reactions you have had to medications, especially to sulfonamide antibiotics or diabetes medications. Contact your doctor at once if you experience signs of an allergic reaction, such as skin rash, itching, difficulty breathing, or swelling of the face and throat.

Allergy desensitization treatment: Tell your doctor if you are undergoing or will undergo desensitization treatment for an allergy. Desensitization treatment reduces the effects of the allergy (e.g., the reaction to bee or wasp stings), but it can sometimes cause a more severe allergic reaction if you are taking ACE inhibitors during the desensitization treatment.

Angioedema: Angioedema is a serious allergic reaction that causes swelling of the hands, feet, ankles, face, lips, tongue, or throat. If you experience any of these when you take lisinopril – hydrochlorothiazide, stop taking the medication at once and get immediate medical attention.

You should avoid taking any other medications in the ACE inhibitors class of medications. People who have had angioedema caused by other substances may be at increased risk of angioedema when they take an ACE inhibitor.

Cholesterol: Increases in cholesterol and triglyceride levels may occur when taking hydrochlorothiazide. At the doses used in lisinopril – hydrochlorothiazide, this rarely causes problems. However, if you have high cholesterol, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Cough: People taking lisinopril may develop a dry, persistent cough that usually disappears only after stopping or lowering the lisinopril dose of this medication. Inform your doctor of any cough that does not seem to be related to a usual cause.

Diabetes: Hydrochlorothiazide may make it more difficult for people who have diabetes to control their blood sugar. High blood sugar may occur, glucose tolerance may change, and diabetes may worsen. A dose adjustment of diabetes medications, including insulin, may be required. If you have diabetes, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.  An adjustment to doses of antidiabetic medications may be required.

Drowsiness/reduced alertness: Lisinopril – hydrochlorothiazide can cause dizziness or tiredness and you should not perform tasks such as driving or using machines that require special attention until you know how the medication will affect you.

Fluid and electrolyte balance: Increases in blood levels of potassium may occur for some people who take lisinopril. The levels of electrolytes such as calcium, potassium, sodium, magnesium, and chloride can be affected by treatment with hydrochlorothiazide. Your doctor will periodically check to see if these are in balance by requesting blood tests. Warning signs of fluid and electrolyte imbalance include:

• confusion
• drowsiness
• dryness of mouth
• lethargy
• low blood pressure
• muscle pains or cramps
• muscular fatigue
• nausea
• racing heartbeat
• restlessness
• seizures
• thirst
• vomiting
• weakness

Glaucoma: This medication may cause the symptoms of glaucoma (increased pressure in the eye) to become worse. Report any changes in vision to your doctor as soon as possible while you are taking this medication.

Gout: Hydrochlorothiazide may increase the level of uric acid in the body, which may result in an attack of gout. If you have a history of gout, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you develop painful, warm, and swollen joints, contact your doctor.

Heart or blood vessel disease: If you have a narrowing of the aorta (aortic stenosis) or the kidney artery (renal artery stenosis), or increased thickness of the heart muscle (hypertrophic cardiomyopathy), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Kidney function: Decreased kidney function or kidney disease can cause this medication to build up in the body, causing side effects. Lisinopril may cause decreased kidney function. Certain people, such as those with narrowed blood vessels in their kidneys, or those with severe congestive heart failure may be more likely to experience this complication. The use of other diuretics (water pills), nonsteroidal anti-inflammatory drugs (NSAIDs), or aliskiren, may further increase risk of kidney trouble for people already at risk for this problem. If you have reduced kidney function, renal artery stenosis (narrowing of blood vessels in the kidneys), or congestive heart failure, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you have reduced kidney function, you may require lower doses of this medication.

If you experience symptoms of decreased kidney function, such as puffy hands, face, or feet; high blood pressure; unusual muscle cramping; or darkened urine, this medication may be affecting how well your kidneys are working. If you notice any of these symptoms, contact your doctor as soon as possible.

Liver function: Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects. This medication can also worsen liver function. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication. If you notice any signs of liver problems (e.g., abdominal pain, itching of skin, or yellow eyes or skin, loss of appetite, vomiting), contact your doctor immediately.

Low blood pressure: Occasionally, blood pressure drops too low after taking lisinopril – hydrochlorothiazide. This usually happens after the first or second dose or when the dose is increased. It is more likely to occur for people who take water pills, have a salt-restricted diet, are on dialysis, are taking the medication aliskiren, are suffering from diarrhea or vomiting, or have been sweating excessively and not drinking enough liquids. If low blood pressure causes you to faint or feel lightheaded, contact your doctor.

Low white blood cell count: This medication can decrease the number of white blood cells, which help the body to fight infection. Your doctor may periodically request blood tests to monitor your levels of white blood cells. If you notice more frequent signs of infection (e.g., fever, chills, or sore throat), contact your doctor immediately.

Lupus: There have been reports of a worsening or activation of lupus for people taking hydrochlorothiazide. If you have lupus, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Sensitivity to sunlight: This medication may increase the sensitivity of the skin to sunlight, increasing the risk of sunburn. Avoid exposure to sunlight for long periods of time, particularly between the hours of 10 am and 2 pm, while you are taking this medication. Wear a broad-spectrum sunscreen and lip balm with an SPF of 30 or greater. If you notice any unusual skin rash or peeling, contact your doctor immediately.

Skin cancer: Recent reviews of hydrochlorothiazide have connected long term use of the medication with an increased risk of developing non-melanoma skin cancer. This often appears as a lump or discoloured patch of skin that slowly changes appearance or size. Check your skin regularly for unusual growths or discolouration and report any changes to your doctor as soon as possible. Talk to your doctor about any concerns you may have.

Surgery or anesthesia: Tell your doctor or dentist that you are taking lisinopril – hydrochlorothiazide before you are given a local or general anaesthetic. When combined with some anesthetics, this medication may cause a short-term drop in blood pressure.

Pregnancy: Pregnant women should not take this medication. When used during pregnancy, lisinopril can cause injury or death to the developing baby. If you become pregnant, stop taking this medication and contact your doctor immediately.

Breast-feeding: Medications similar to lisinopril pass into breast milk and hydrochlorothiazide passes into breast milk. If you are breast-feeding and are taking lisinopril – hydrochlorothiazide, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of this medication have not been established for children. It is not recommended for children to use this medication.

Seniors: Seniors have an increased risk of experiencing side effects when taking quinapril lisinopril – hydrochlorothiazide due to reduced kidney function. Lower doses may be necessary to minimize side effects.

What other drugs could interact with this medication?

There may be an interaction between lisinopril – hydrochlorothiazide and any of the following:

• acetylsalicylic acid (ASA)
• aclidinium
• alcohol
• aldesleukin
• aliskiren
• allopurinol
• alpha-adrenergic blocking agents (e.g., alfuzosin, doxazosin, prazosin, terazosin)
• alpha-agonists (e.g., clonidine, methyldopa)
• angiotensin converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
• amiodarone
• amphetamines (e. g., dextroamphetamine, lisdexamfetamine)
• angiotensin receptor blockers (ARBs; losartan, valsartan, candesartan)
• antacids (e.g., aluminum hydroxide, calcium carbonate, magnesium hydroxide)
• antihistamines (e.g., azelastine, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
• antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
• apomorphine
• atropine
• azathioprine
• azelastine
• barbiturates (e.g., butalbital, phenobarbital)
• belladonna
• benztropine
• beta-blockers (e.g., atenolol, carvedilol, propranolol)
• beta-2 agonists (e.g., salbutamol, formoterol, terbutaline)
• brimonidine
• calcitriol
• calcium carbonate, calcium citrate
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• carbamazepine
• cholestyramine
• colestipol
• conivaptan
• oral corticosteroids (e. g., dexamethasone, hydrocortisone, prednisone)
• cyclobenzaprine
• cyclophosphamide
• cyclosporine
• desmopressin
• dexmethylphenidate
• diabetes medications (e.g., acarbose, canagliflozin, glyburide, lixisenatide, insulin, metformin, rosiglitazone, saxagliptin)
• diazoxide
• digoxin
• disopyramide
• domperidone
• drospirenone
• duloxetine
• eplerenone
• everolimus
• flavoxate
• ginger
• ginseng
• glycopyrrolate
• grass pollen extract
• guanfacine
• heparin
• hydralazine
• inhaled corticosteroids (e.g., budesonide, ciclesonide, fluticasone)
• ipratropium
• iron dextran complex
• iron supplements
• ivabradine
• lanthanum
• levodopa
• licorice
• lithium
• low molecular weight heparins (LMWHs; e.g., dalteparin, enoxaparin, tinzaparin)
• medications that increase blood levels of potassium (e. g., potassium chloride, salt substitutes containing potassium)
• methylphenidate
• monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
• multivitamins/minerals with ADE
• nabilone
• narcotic pain relievers (e.g., codeine, fentanyl, morphine, tramadol)
• nitroglycerin
• nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen)
• obinutuzumab
• octreotide
• orphenadrine
• other diuretics (water pills; e.g., furosemide, triamterene)
• oxcarbazepine
• oxybutynin
• pentoxifylline
• phenytoin
• phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• porfimer
• pramipexole
• pregabalin
• riociguat
• ropinirole
• sacubitril
• scopolamine
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline)
• sirolimus
• sodium phosphates
• temsirolimus
• tiotropium
• tizanidine
• tolterodine
• tolvaptan
• topiramate
• tretinoin
• tricyclic antidepressants (e. g., amitriptyline, clomipramine, desipramine, trimipramine)
• trimethoprim
• umeclidinium
• vitamin D
• yohimbine

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2023. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Mylan-Lisinopril-HCTZ

Fixed combination of lisinopril and hydrochlorothiazide in the treatment of arterial hypertension | Dobrovolsky A.V.

The results of pharmacoepidemiological studies conducted in recent years indicate that patients with arterial hypertension (AH) in most cases have to simultaneously take two or more antihypertensive drugs to achieve optimal control of blood pressure (BP) levels. Thus, according to the PIFAGORE II study, 82% of patients take more than one drug that reduces blood pressure [1]. Significant advantages of combination therapy are the enhancement of the antihypertensive effect due to the multidirectional action of different components on the pathogenetic mechanisms of the development of hypertension, a decrease in the incidence of side effects, both due to lower doses of combined antihypertensive drugs, and due to the mutual neutralization of these effects; providing the most effective organoprotection (better protection of the so-called target organs) and reducing the risk and number of cardiovascular complications [4]. However, not every combination of antihypertensive drugs can be considered justified. In accordance with the Russian National Guidelines for the Treatment of Arterial Hypertension [6] and the recommendations of the European Society of Cardiology [8], a rational combination of antihypertensive drugs must meet the following requirements: the presence of different and complementary mechanisms of action, evidence of greater effectiveness of the combined drug compared to the use of each of the components separately, as well as good tolerability of treatment confirmed by controlled studies.

It should be remembered that with the simultaneous appointment of several antihypertensive drugs, the likelihood of non-compliance with the drug regimen increases (especially in the elderly and in patients suffering from several chronic diseases requiring drug therapy). An alternative to complex therapeutic regimens are fixed combinations of drugs. The use of such combined drugs significantly increases adherence to treatment and, as a result, increases the effectiveness of antihypertensive therapy [4].
Among the combined antihypertensive drugs, one of the most common are tablet preparations containing an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic (most often hydrochlorothiazide). The components of this combination affect different links in the pathogenesis of hypertension. Thus, the antihypertensive effect of ACE inhibitors is based on their ability to suppress the activity of angiotensinogen-I-converting enzyme, thus reducing the activity of the renin-angiotensin-aldosterone system. ACE inhibitors reduce the formation of circulating and tissue angiotensin II, thereby weakening its vasoconstrictor and proaggregant action (reducing the release of endothelin from the endothelium and increasing the blood levels of vasodilating agents – bradykinin and prostacyclin), and also reduces the secretion of aldosterone. Thus, the antihypertensive effect of ACE inhibitors is based not only on their direct effect on the regulation of vascular tone and circulating blood volume, but also indirectly through the improvement of the rheological parameters of the latter, such as viscosity, aggregation activity of platelets and erythrocytes. Thiazide diuretics reduce the reabsorption of sodium, potassium, chlorine, magnesium ions, as well as water molecules in the distal nephron (at the same time, the excretion of calcium and uric acid ions is delayed), thus increasing the amount of urine excreted. It is believed that increased natriuresis leads to a decrease in circulating plasma volume, reduces venous return to the heart, and also reduces cardiac output and peripheral vascular resistance. In addition, the hypotensive effect of thiazide diuretics may be associated with a decrease in the reactivity of the cardiovascular system to the effects of circulating catecholamines [2].
Among the numerous representatives of ACE inhibitors, lisinopril, a lysine analog of enalaprylic acid, occupies a leading position [7]. Unlike most other representatives of the considered pharmacological group, lisinopril is not a prodrug, does not undergo biotransformation in the liver and is excreted unchanged by the kidneys. The drug has a fairly variable bioavailability – from 6 to 60% (on average – about 25%). In elderly patients, an increase (approximately 2 times) in the concentration of lisinopril in the blood and AUC is noted compared with younger patients. Complete absorption of the drug does not depend on food intake. Lisinopril is not lipophilic, practically does not bind to plasma proteins, penetrates the blood-brain barrier to a small extent and does not accumulate in tissues (primarily in adipose tissue). The maximum serum concentration is reached after about 6-7 hours and persists for 24 hours. The half-life is 12 hours. A decrease in kidney function slows down elimination, but the slowdown becomes clinically significant only when the glomerular filtration rate drops below 30 ml / min. [5]. The hypotensive effect begins an hour after ingestion, the peak of the effect develops after 4-6 hours, and the duration of action reaches 24 hours, which provides a convenient regimen of administration – once a day.
Hydrochlorothiazide is also currently one of the most widely used thiazide diuretics. The drug is quite quickly, but not completely absorbed from the gastrointestinal tract, in the blood by 40-60% binds to proteins. Penetrates through the hematoplacental barrier and into breast milk. Excreted by the kidneys. The diuretic effect of the drug develops after 30-60 minutes, reaches a maximum after 4-6 hours and persists for 6-12 hours [3]. The hypothetical effect of hypothiazide becomes noticeable after 3-4 days of therapy, and the optimal antihypertensive effect in most cases develops after 3-4 weeks. regular intake of the drug.
The high efficacy of lisinopril in hypertension has been proven in a number of controlled studies. It has been established that, in its hypotensive effect, lisinopril is not inferior or superior to other ACE inhibitors (captopril, enalapril, quinapril) [13,15,40], calcium antagonists (nifedipine, felodipine, isradipine) [16,21,34], b-blockers (atenolol, metoprolol, nebivolol) [10,35,39] and angiotensin II receptor blockers (candesartan, valsartan) [25,31]. It should be noted that the vast majority of the above studies indicate the good tolerability of lisinopril and the rarity of its withdrawal due to adverse events.
It is now considered proven that lisinopril not only effectively lowers blood pressure, but also has a protective effect on the target organs of arterial hypertension. In particular, in the multicenter study SAMPLE (Study on Ambulatory Monitoring of blood Pressure and Lisinopril Evaluation), it was found that the use of lisinopril leads to a regression of left ventricular hypertrophy [27,33]. Similarly, the comparative randomized controlled trial ELVERA (Effects of amlodipine and lisinopril on Left Ventricular mass) demonstrated a significant reduction in left ventricular mass and improvement in diastolic function during long-term (median follow-up, 2 years) lisinopril therapy [42]. Finally, in the randomized CALM study (Candesartan And Lisinopril Microalbuminuria study), it was found that lisinopril reduces urinary albumin excretion in patients with arterial hypertension and diabetes mellitus [31].
A modern antihypertensive drug should not only effectively reduce blood pressure, but also have a positive effect on long-term prognosis, reducing the risk of cardiovascular events and reducing mortality. So, a multicenter randomized open masked study STOP-hypertension 2 (Swedish Trial in Old Patients with Hypertension 2) showed no difference between ACE inhibitors (lisinopril, enalapril), b-blockers (atenolol, metoprolol CR, pindolol), diuretics (hydrochlorothiazide, amiloride ) and calcium antagonists (felodipine, isradipine) by their effect on reducing the risk of myocardial infarction, stroke and overall mortality in elderly patients with arterial hypertension [19]. The results of the well-known large-scale controlled study ALLHAT (Antihypertensive and Lipid-Lowering Treatment to prevent Heart Attack Trial) show no significant differences in the ability to prevent the primary combined endpoint (myocardial infarction and death from cardiovascular causes) and the effect on overall mortality between lisinopril, amlodipine, chlorthalidone and doxazosin [9].
The hypotensive effect of hydrochlorothiazide and its effectiveness in preventing cardiovascular events have also been confirmed by the results of many controlled clinical trials. In one of the earliest placebo-controlled studies MRFIT (Multiple Risk Factor Intervention Trial) found that long-term therapy with hydrochlorothiazide significantly reduces the incidence of myocardial infarction in patients with hypertension [32]. Placebo-controlled study STOP-Hypertension (Swedish Trial in Old Patients with Hypertension) showed that hydrochlorothiazide therapy effectively lowers blood pressure in elderly patients, and also reduces the risk of cardiovascular, cerebrovascular and overall mortality [12]. In a randomized clinical trial HAPPHY (Heart Attack Primary Prevention in Hypertension trial) it was found that hydrochlorothiazide is comparable to b-adrenergic blockers (atenolol, metoprolol) in hypotensive effect, as well as in a favorable effect on overall mortality, the frequency of coronary and cerebrovascular events [44] . It has also been established that hydrochlorothiazide is equally effective in lowering blood pressure as modern drugs from the group of angiotensin II receptor blockers candesartan (ALPINE study [24]) and telmisartan (ARAMIS study [28]).
The combined use of lisinopril and hydrochlorothiazide (in the form of separate tablet dosage forms) for the correction of arterial hypertension is highly effective [11,37]. However, of particular interest are studies that have studied the effect of a fixed combination of these pharmacological agents. It should be noted that this combination is very favorable from the point of view of clinical pharmacology. Studies conducted on healthy volunteers [41] and in elderly patients with hypertension and impaired renal function [22] showed that lisinopril and hydrochlorothiazide contained in one tablet do not enter into drug interactions with each other and do not change the pharmacokinetic characteristics of each other. .
The results of the studies carried out testify to the high efficiency of such drugs [26]. In particular, Gerc V. et al. it was found that tablet preparations containing lisinopril and hydrochlorothiazide normalize blood pressure in 81.5% of patients with mild to moderate arterial hypertension [18]. According to Vegazo Garcia O. et al., the fixed combination of lisinopril and hydrochlorothiazide in more than half of the cases allows to steadily reduce blood pressure to normal levels in patients with high arterial hypertension, poorly controlled by other drugs [43].
It has been established that the considered combination has a protective effect on the target organs of arterial hypertension. Already after 12 weeks. taking a fixed combination of lisinopril and hydrochlorothiazide decreases left ventricular hypertrophy [17]. In addition, against the background of this therapy, there is a normalization of lipid and carbohydrate metabolism [43].
The fixed combination of lisinopril and hydrochlorothiazide has a more pronounced hypotensive effect than each of the components separately [20,23,36]. Several studies have compared the effectiveness of the fixed combination of lisinopril and hydrochlorothiazide with other combination drugs. It has been established that preparations containing 10 mg of lisinopril and 12.5 mg of hydrochlorothiazide are comparable in their hypotensive effect with dosage forms containing 8 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide [29]. According to other studies, the combination of 20 mg of lisinopril and 12.5 mg of hydrochlorothiazide provides more stable control of blood pressure during the day than the combination of 50 mg of captopril and 25 mg of hydrochlorothiazide [30,38], and has a comparable hypotensive effect with fixed combinations of atenolol 100 mg + chlorthalidone 25 mg” and “verapamil 180 mg (sustained release formulation) + trandolapril 2 mg” [de Leeuw PW, 1997]. In all studies described, the tolerability of the combination of lisinopril with hydrochlorothiazide was comparable to that of other combinations of antihypertensive agents.
Thus, a fixed combination of lisinopril and hydrochlorothiazide (on the domestic market, this combination is represented by Co-Diroton® (Gedeon Richter company)) can be used as initial therapy in patients with mild and moderate arterial hypertension [6], in individuals with severe left ventricular hypertrophy, overweight and carbohydrate metabolism disorders [4]. In addition, the considered combined drug can be successfully used in high arterial hypertension, refractory to other antihypertensive drugs. Favorable tolerability profile and the possibility of prescribing 1 time / day. make the fixed combination of lisinopril and hydrochlorothiazide a very valuable tool in the hands of a practicing cardiologist.

Literature
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2 Galyavich A.S. Fixed combinations of antihypertensive drugs. Сonsilium Medicum 2011 13; 1:24–27.
3 Hydrochlorothiazide: instructions and use. http://www.rlsnet.ru/mnn_index_id_89.htm
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15 Diamant M., Vincent H.H. Lisinopril versus enalapril: evaluation of trough:peak ratio by ambulatory blood pressure monitoring. J Hum Hypertens 1999;13(6):405–12.
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18 Gerc V., Begovic B., Vehabovic M., et al. Fixed combination lisinopril plus hydro-chlorothiazide in the treatment of essential arterial hypertension: an opened, multi-centre, prospective clinical trial. Bosn J Basic Med Sci. 2007;7(4):377–82.
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20 Hart W. Lisinopril–hydrochlorothiazide combination compared with the monocomponents inelderly hypertensive patients. J Hum Hypertens. 1991;5 Suppl 2:85–9.
21 Jensen H.A. Efficacy and tolerability of lisinopril compared with extended release felodipine in patients with essential hypertension. Danish Cooperative Study Group. Clin Exp Hypertens 1992;14(6):1095–110;
22 Laher M.S., Mulkerrins E., Hosie J., et al. The effects of age and renal impairment on the pharmacokinetics of co-administered lisinopril and hydrochlorothiazide. J Hum Hypertens. 1991;5 Suppl 2:77–84.
23 Lang H. The results of a large multicentre study comparing low–dose lisinopril–hydrochlorothiazide with the monocomponents. J Hum Hypertens. 1991;5 Suppl 2:73–6.
24 Lindholm L.H., Persson M., Alaupovic P., et al. Antihypertensive treatment and Lipid Profile In a North of Sweden Efficacy evaluation. J Hypertens 2003;21:1563–74
25 Malacco E., Santonastaso M., Vari N.A., et al. Comparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in combination with a diuretic, for the treatment of hypertension: the Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril (PREVAIL) study. Clin Ther 2004;26:855–65
26 Mancia G., Grassi G. Antihypertensive effects of combined lisinopril and hydrochlortiazide in elderly patients with systolic hypertension: results of a multicenter trial. J. Cardivasc. Pharmacol. 1997, 30(5) 548–553.
27 Mancia G., Zanchetti A., Agabiti-Rosei E., et al. Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment–induced regression of left ventricular hypertrophy. Circulation 1997;95:1464–70.
28 Manolis A. J., Reid J.L., de Zeeuw D., et al. Angiotensin II receptor antagonist telmisartan in isolated systolic hypertension (ARAMIS) study: efficacy and safety of telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or placebo. J Hypertens 2004;22:1–5.
29 McInnes G.T., O’Kane K.P., Istad H, et al. Comparison of the AT1–receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients. J Hum Hypertens. 2000 Apr;14(4):263–9.
30 Milon H., Baleydier A. [Comparison of antihypertensive and metabolic effects of lisinopril 20 mg/hydrochlorothiazide 12.5 mg fixed combination and captopril 50 mg/hydrochlorothiazide 25 mg fixed combination]. therapy. 1997; 52(3):195–205.
31 Mogensen C.E., Neldan S., Tikkanen I., et al. Randomized controlled trial of dual blockade of renin–angiotensin system in patients with hypertension, microalbuminuria, and non–insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study BMJ 2000;321:1440–4.
32 MRFIT research group. Multiple Risk Factor Intervention Trial. Risk factor changes and mortality results. JAMA 1982;248:1465–77.
33 Omboni S., Fogari R., Palatini P., et al. Reproducibility and clinical value of the trough-to-peak ratio of the antihypertensive effect. Evidence from the Sample study Hypertension 1998;32:424–9.
34 Os I., Bratland B., Dahlof B. at al. Lisinopril or nifedipine in essential hypertension? A Norwegian multicenter study on efficacy, tolerability and quality of life in 828 patients. J Hypertens 1991; 9(12): 1097–104
35 Pannier B.E., Garabedian V.G., Madonna O., et al. Lisinopril versus atenolol: decrease in systolic versus diastolic blood pressure with converting enzyme inhibition. Cardiovasc Drugs Ther. 1991; 5(4):775–81.
36 Pathe M. Lisinopril–hydrochlorothiazide combination vs lisinopril for the treatment of hypertension. J Hum Hypertens. 1991 Dec;5 Suppl 2:53–4.
37 Pool J.L., Gennari J., Goldstein R. e.a. Controlled multicenter study of the antihypertensive effects of lisinopril, hydrochlorthiazide and lisinopril plus hydrochlorthiazide in the treatment of 349 patients with mild to moderate tssential hypertension. J. Cardiovasc. Pharmacol. 1987 9(suppl.3) S 36–54.
38 Rappelli A. Controlling hypertension: lisinopril–hydrochlorothiazide vs captopril–hydrochlorothiazide. An Italian multicentre study. J Hum Hypertens. 1991 Dec;5 Suppl 2:55–7; discussion 57–8.
39 Rosei E.A., Rizzoni D., Comini S. et al. Evaluation of the efficacy and tolerability of nebivolol versus lisinopril in the treatment of essential arterial hypertension: a randomized, multicentre, double-blind study. Blood Press Suppl. 2003; 1:30–5.
40 Rumboldt Z., Simunic M., Bagatin J., et al. Controlled multicentre comparison of captopril versus lisinopril in the treatment of mild–to–moderate arterial hypertension. Int J Clin Pharmacol Res. 1993;13(1):35–41.
41 Swaisland A.J. The pharmacokinetics of co-administered lisinopril and hydrochlorothiazide. J Hum Hypertens. 1991;5 Suppl 2:69–71.
42 Terpstra W.F., May J.F., Smit A.J. Long-term effects of amlodipine and lisinopril on left ventricular mass and diastolic function in elderly, previously untreated hypertensive patients: the ELVERA trial J Hypertens 2001;19:303–9
43 Vegazo Garcia O. , Llisterri Caro J.L., Jimenez Jimenez F.J., et al.. [Effectiveness of combined therapy at set doses in a cohort of hypertense patients not controlled by single therapy]. Aten Primaria. 2003 28;31(3):163–9.
44 Wilhelmsen L., Berglund G., Elmfeldt D. et al Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial J Hypertens 1987;5:561-72.

Lisinopril / HCTZ – Instructions for use, dosage, composition, side, side effects / PilLintrip

Symptomatic hypotension

Symptomatic hypotension rarely occurs in uncomplicated patients with hypertension, but more often occurs when the patient is depleted in volume, for example ,. through diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting, or severe renin-dependent hypertension. In such patients, serum electrolytes should be measured regularly at appropriate intervals. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustments should be monitored under close medical supervision. Particular attention is given to patients with ischemic heart disease or cerebrovascular disease, since an excessive drop in blood pressure can lead to myocardial infarction or cerebrovascular accident.

If hypotension occurs, the patient should be placed on their back and, if necessary, an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication for further doses. After restoration of effective blood volume and pressure, it may be possible to restore therapy at a reduced dosage; or one of the components can be used separately.

Some patients with heart failure with normal or low blood pressure may experience an additional decrease in systemic blood pressure with lisinopril. This effect is expected and is not usually a reason to stop treatment. If hypotension becomes symptomatic, dose reduction or discontinuation of lisinopril hydrochlorothiazide may be required.

Aortic and mitral valves stenosis / Hypertrophic cardiomyopathy

As in the case of other ACE inhibitors, lysinopril should be prescribed with caution to patients with mitral valve stenosis and constituent of the left ventricle, such as aortic stenosis or hypertrophic cardiomiopathia.

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

There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS is not recommended with the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren.

If dual block therapy is considered absolutely necessary, this should only be done under professional supervision and with 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.

Renal insufficiency

Thiazides may not be suitable for diuretic use in patients with renal insufficiency and creatinine clearance values ​​of 30 ml/min or less (corresponding to moderate or severe renal insufficiency).

Lisinopril/hydrochlorothiazide should not be given to patients with renal insufficiency (creatinine clearance less than or equal to 80 ml/min) until titration of the individual components shows that the doses present in the combination tablet are required.

In patients with heart failure, hypotension after initiation of ACE inhibitor therapy may further impair renal function. Acute renal failure, usually reversible, has been reported in this situation.

Some patients with bilateral renal artery stenosis or arterial stenosis have an increase in blood urea and serum creatinine to a single kidney receiving ACE inhibitors, which is usually reversible upon discontinuation of therapy. This is especially likely in patients with renal insufficiency. If there is also renovascular hypertension, there is an increased risk of severe hypotension and renal failure. In these patients, treatment should be initiated under close medical supervision with low doses and careful dose titration. Since diuretic treatment may contribute to the above factors, renal function should be monitored during the first weeks of lisinopril/hydrochlorothiazide therapy.

Some hypertensive patients who do not have overt pre-existing kidney disease usually experience mild and transient increases in blood urea and serum creatinine when lisinopril is administered concomitantly with a diuretic.

This is more common in patients with pre-existing renal insufficiency. Dose reduction and/or discontinuation of the diuretic and/or lisinopril may be required.

Previous diuretic therapy

Diuretic therapy should be discontinued 2-3 days prior to starting treatment with lisinopril/hydrochlorothiazide. If this is not possible, treatment with lisinopril alone should be initiated at a dose of 5 mg.

Kidney transplant

Should not be used as there is no experience with patients who have recently had a kidney transplant.

anaphylactoid reactions in hemodialysis patients

Lisinopril/hydrochlorothiazide is not indicated in patients requiring dialysis for renal failure.

Anaphylactoid reactions have been reported in patients undergoing certain hemodialysis procedures (eg. with high flux AN 69 membranes and during low density lipoprotein (LDL) – dextran sulfate apheresis) and concomitantly with an ACE inhibitor. In these patients, consideration should be given to using a different type of dialysis membrane or class of antihypertensive agents.

Anaphylactoid reactions associated with low-density lipoprotein (LDL) apheresis

In rare cases, patients treated with dextran sulfate with ACE inhibitors during low-density lipoprotein (LDL) apheresis have shown life-threatening anaphylactic reactions. These symptoms can be avoided by temporarily stopping treatment with ACE inhibitors before any apheresis.

liver dysfunction

Thiazides should be used with caution in patients with hepatic impairment or advanced liver disease, as minor changes in fluid and electrolyte balance may cause hepatic coma. Rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving lisinopril/hydrochlorothiazide and developing jaundice or a significant increase in liver enzymes should discontinue lisinopril/hydrochlorothiazide and receive adequate medical supervision.

Surgery / Anesthesia

In patients who have undergone major surgery or received antihypertensive drugs during anesthesia, lisinopril may block the formation of angiotensin II as a result of compensatory renin release. If due to this mechanism, it is believed that the appearance of hypotension can be corrected by increasing the volume.

Metabolic and endocrine effects

ACE inhibitors and thiazide therapy may affect glucose tolerance. Dose adjustment of antidiabetic drugs, including insulin, may be required. In diabetics treated with an oral antidiabetic or insulin drug, glycemic levels should be closely monitored with an ACE inhibitor during the first month of treatment. Latent diabetes mellitus may occur during thiazide therapy.

Elevated cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.

Thiazide therapy may cause hyperuricemia and/or gout in some patients. However, lisinopril may increase uric acid and thus weaken the hyperuricemic effects of hydrochlorothiazide.

electrolyte imbalance

As with any patient receiving diuretic therapy, periodic serum electrolyte determination should be performed at appropriate intervals.

Thiazides, including hydrochlorothiazide, may cause fluid or electrolyte imbalances (hypokalemia, hyponatremia, and hypochloremic alkalosis). Warning signs of fluid or electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, muscle pain or spasm, muscle fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting. Dilution of hyponatremia may occur in edematous patients during hot weather. Deficiency is usually mild and does not require treatment. Thiazides have been shown to increase urinary magnesium excretion, which can lead to hypomagnesemia.

Thiazides may reduce urinary calcium excretion and cause intermittent and slight increases in serum calcium. Pronounced hypercalcemia may indicate latent hyperparathyroidism. Thiazides should be discontinued prior to testing for parathyroid function.

Hyperkalemia

An increase in serum potassium has been observed in some patients treated with ACE inhibitors, including lisinopril. Patients at risk of developing hyperkalemia include patients with renal insufficiency, diabetes mellitus, or patients taking potassium-sparing diuretics, potassium supplements, or salt substitutes, or patients taking other medications that increase serum potassium levels (eg, heparin, trimethoprim/sulfamethoxazole combination, also known as cotrimoxazole). If concomitant use of the above agents is deemed appropriate, regular monitoring of serum potassium levels is recommended.

Diabetic

In diabetics treated with an oral antidiabetic or insulin drug, glycemic control with an ACE inhibitor should be closely monitored during the first month of treatment.

Hypersensitivity/angioedema

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has rarely been reported in patients treated with ACE inhibitors, including lisinopril. This can happen at any time during therapy. In such cases, lisinopril should be discontinued immediately and appropriate treatment and monitoring initiated to ensure complete resolution of symptoms before the patient is discharged. Even in cases where there is only swelling of the tongue without difficulty breathing, patients may require long-term follow-up, as treatment with antihistamines and corticosteroids may not be sufficient.

Mortality from angioedema associated with laryngeal or tongue edema has been reported very rarely. Airway obstruction may occur in patients with involvement of the tongue, glottis, or larynx, especially in patients with a history of respiratory surgery. In such cases, emergency treatment should be carried out immediately. This may include administering epinephrine and/or maintaining a normal airway. The patient should be under strict medical supervision until complete and permanent resolution of symptoms occurs.

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

Patients with a history of angioedema who are not associated with ACE inhibitor therapy may have an increased risk of angioedema while taking an ACE inhibitor.

Patients who are taking mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) may have an increased risk of angioedema (eg, swelling of the airways or tongue with or without airway obstruction) concomitantly.

Patients receiving thiazides may have a history of hypersensitivity reactions with or without allergies or asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides.

Desensitization

Patients who received ACE inhibitors during desensitization treatment (eg. Hymenoptera venom) showed persistent anaphylactoid reactions. These reactions were prevented in the same patients when ACE inhibitors were temporarily hidden, but they reappeared in case of inadvertent replenishment.

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. Neutropenia is rare in patients with normal renal function and no other complicating factors. Neutropenia and agranulocytosis are reversible after stopping the ACE inhibitor. Lisinopril should be used with extreme caution in patients with collagen disorders, immunosuppressive therapy, allopurinol or procainamide treatment, or a combination of these complex factors, especially in renal insufficiency. Some of these patients developed severe infections, which in some cases did not respond to intensive antibiotic therapy. When lisinopril is used in such patients, regular monitoring of the white blood cell count is recommended and patients should be instructed to report signs of infection.

Race

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

As with other ACE inhibitors, lisinopril may be less effective in lowering blood pressure in black patients than in non-black patients, possibly due to the higher prevalence of low renin conditions in the black hypertensive population.

Cough

Cough has been reported with the use of ACE inhibitors. The cough is characteristic of unproductiveness, persistence, and resolves upon discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

Lithium

The combination of ACE inhibitors and lithium is not generally recommended.

Anti-doping test

The hydrochlorothiazide contained in this preparation may lead to a positive test leading to an anti-doping test.

Pregnancy

ACE inhibitors should not be started during pregnancy.