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

The choice of a fixed combination of lisinopril and hydrochlorothiazide in the treatment of arterial hypertension | Savenkov M.P., Ivanov S.N., Solomonova L.A., Savenkova A.M., Ivanov S.V.

Currently, due to the active introduction into the practice of treating arterial hypertension (AH) of a wide range of drug combinations fixed in one tablet, the practitioner is increasingly faced with the problem of their choice. In accordance with modern recommendations, the reasons for the combined use of drugs are the presence of different and complementary mechanisms of action, evidence of greater effectiveness of the combination, as well as good tolerability of treatment and a lower risk of side effects [1]. The most common fixed combination for the treatment of hypertension is the combination of an ACE inhibitor with a thiazide diuretic [2]. However, the combination of an ACE inhibitor with a calcium channel blocker (CCB), a CCB with a b-blocker (BAB), a BAB with a diuretic, and others are beginning to compete with this combination. The evidence base is accumulating, indicating the effectiveness of the listed antihypertensive combinations, which makes it difficult to differentiate them based on traditional criteria that take into account the age of patients, their race, the presence of target organ damage and associated clinical conditions. Along with the choice of drugs, their correct dosing plays an important role. The latter presents certain difficulties associated with the need to titrate the therapeutic effect with a subordinate change in the dosages of the combination components. The available clinical experience with the use of fixed drugs indicates that the treatment of patients with hypertension should be carried out according to certain indications and with the help of control methods that take into account the mechanisms and specifics of the action of the drug combination.

The use of a fixed combination of an ACE inhibitor and a diuretic suggests that the patient has hypertension with fluid and electrolyte disturbances. In accordance with the modern concept of cardiorenal relationships, renal mechanisms are age dependent and are observed in all patients with AH at a certain stage of the disease [3]. For this reason, ACE inhibitors, which have a triple (vasodilating, diuretic and sympatholytic) effect due to a decrease in the formation of angiotensin II, are most widely used in practice to reduce elevated blood pressure. Limitations in the use of these drugs are associated with the possible development of cough (1-3%), pregnancy and renal artery stenosis. The leading position among the numerous representatives of ACE inhibitors is lisinopril, an active hydrophilic drug with a long (more than 24 hours) action that does not require primary metabolic activation in the liver and does not accumulate in adipose tissue [3,4,5]. These properties provided the benefits of the drug in the morning hours, in obese patients, when combined with other drugs, as well as in various comorbid conditions [6-8]. Conducted multicenter studies have confirmed the ability of lisinopril to improve the prognosis of patients with cardiovascular disease and their quality of life [5]. Lisinopril is taken once a day, and with fluctuations in daily dosage from 5 to 20 mg, effective control of blood pressure can be achieved in 60% of cases or more.
In the Russian Federation, the first representative of lisinopril was Diroton® by Gedeon Richter, Hungary. Our many years of experience in the use of lisinopril (Diroton) indicates that monotherapy can effectively control blood pressure, mainly at the initial stages of the formation of hypertension, in patients with low and moderate risk of developing cardiovascular complications (CVD), as well as in relatively stable meteorological conditions. The antihypertensive effect of lisinopril is reduced in patients with a long history of hypertension and a high risk of cardiovascular events, especially in active smokers with signs of nephropathy. The effectiveness of the drug also decreases during weather-unstable (winter-spring) seasonal periods against the background of sharp fluctuations in atmospheric pressure, humidity and air temperature [9]. Due to the risk of increased side effects, increasing the daily dose of lisinopril by more than 20 mg is not advisable. In case of insufficient effectiveness of treatment, it is necessary to transfer the patient to the combined use of lisinopril with an antihypertensive drug of a different mechanism of action, in particular, a thiazide diuretic or CCB amlodipine.
The use of a thiazide diuretic in combination with lisinopril leads to an increase in the antihypertensive effect and a decrease in the risk of adverse reactions. It is believed that the decrease in elevated blood pressure when using a diuretic occurs as a result of the removal of water and sodium chloride, which leads to a decrease in circulating blood volume and cardiac output, as well as a decrease in vascular tone, total peripheral resistance as a result of a decrease in the response of the vascular wall to catecholamines and angiotensin II .
More than half a century of experience in clinical use has made it possible to formulate two basic rules for the use of diuretics: these drugs should be prescribed only in the presence of water and electrolyte disorders and in the minimum effective doses. The last provision is extremely important, because. can significantly reduce the risk of side effects with long-term (actually lifelong) use of diuretics in the treatment of hypertension. A large number of multicenter studies have shown that long-term use of thiazide (hydrochlorothiazide) and thiazide-like (indapamide) diuretics in low doses, respectively, in the ranges of 6.25-25 mg and 0.625-2.5 mg is safe [10]. At the same time, it should be noted that, in fact, a four-fold range of diuretic dosage fluctuations is quite wide, and therefore the problem of choosing the minimum effective antihypertensive dose remains relevant, especially considering that the diabetogenic effect with very long-term use of tazide diuretics is not completely excluded, as there is a corresponding warning in the recommendations of the European Society of Cardiology [1]. Diuretics remain the treatment of choice in the treatment of isolated systolic hypertension in elderly patients; they are widely used in practice to enhance the antihypertensive effect of other drugs, primarily ACE inhibitors. The feasibility and necessity of using a combination of an ACE inhibitor with a thiazide diuretic for more effective control of blood pressure and the prevention of vascular complications (in particular, stroke) has been convincingly proven by multicenter studies [11].
For more convenient administration and increased adherence of patients to treatment, ACE inhibitors and diuretics are increasingly being used in one tablet in fixed therapeutic doses. Currently, a large group of such combined drugs has been replenished with another representative – a combination of an ACE inhibitor lisinopril with hydrochlorothiazide. The effectiveness of this combination was confirmed at the end of the last century, when during the examination and treatment of more than 800 patients with hypertension, it was shown that when hydrochlorothiazide, inferior in its antihypertensive activity, is added to lisinopril, a significantly greater decrease in elevated blood pressure occurs, while the risk of developing hypokalemia decreases. It was also found that the use of lisinopril at a dose of 10 mg with hydrochlorothiazide 12.5 mg is optimal. This combination is especially effective in elderly patients [12-14].
In the Russian Federation, a fixed combination of lisinopril with hydrochlorothiazide in doses of 10/12.5 and 20/12.5 mg is registered under the trade name Co-Diroton® (Gedeon Richter, Hungary). The accumulating, including our own, experience with the use of Co-Diroton indicates the prospects of its use for the treatment of hypertension. Taking into account the complex cardiorenal mechanism of action of Co-Diroton, its effectiveness was studied using the method of combined 24-hour monitoring of blood pressure and diuresis (CSMAD) developed by us [15].
KSMADD includes simultaneous monitoring of blood pressure according to the generally accepted method and diuresis in the form of a percentage of the volume of urine excreted and fluid consumed for the morning, noon, evening and night periods of time [15]. The main indicator of KSMADD is the tensiodiuretic ratio (TDS) – a complex indicator that reflects the average value of systolic blood pressure for a given period of time (t), and diuresis as a percentage of the ratio of excreted urine to fluid consumed over the same period (TDSt = sred.AP syst. mm Hg / diuresis %). In healthy individuals, normal TDS values ​​range from 120–135 mm Hg / 75–100%. TDS allows you to determine the relationship between blood pressure and diuresis at different times of the day.
The experience of using KSMAD in more than 200 patients with cardiovascular pathology suggests that the magnitude of TDS can be used to evaluate the effectiveness of treatment for hypertension, including a thiazide diuretic in the dynamics of diuresis (Fig. 1). The study during the QSMAD diuresis revealed the presence of daytime fluid retention in patients with AH, followed by its more intense release at night (Fig. 1). Activation of nocturnal diuresis in patients occurred against the background of elevated blood pressure.
The revealed relationships between diuresis and blood pressure make it possible to understand the reason for the absence of a nocturnal decrease in blood pressure in hypertensive patients and to evaluate daytime fluid retention as a manifestation of water imbalance, justifying the need to prescribe a thiazide diuretic for antihypertensive purposes. The appointment of the latter leads to a decrease in blood pressure due to the activation of daytime diuresis and a decrease in night diuresis (Fig. 1). The use of KSMADD allows you to justify the choice and evaluate the effectiveness of the fixed combination of lisinopril with hydrochlorothiazide.
This combination (Ko-Diroton®, Gedeon Richter, Hungary) was used in 15 patients (11 men and 4 women) aged 56–75 years with hypertension of II–III degree, with a high gradation of risk, in whom preliminary treatment was carried out for 3–4 weeks of monotherapy with lisinopril (Diroton®, Gedeon Richter, Hungary) at a daily dose of 10–20 mg, was not effective enough, according to the KSMADD. Of the 15 patients, 9 were long-term smokers, 8 patients were overweight. All patients led a sedentary lifestyle. 5 patients had stable exertional angina I-II functional class. The study was conducted in the autumn-winter period against the background of unstable weather conditions in the form of periodic fluctuations in atmospheric pressure at a rate of > 0.5 mm.h, changes in outdoor air temperature (from +15 to -20°C) and air humidity from 55 to 98%. Existing risk factors in patients and changes in weather conditions were possible reasons for the insufficient effectiveness of lisinopril monotherapy. Co-Diroton was prescribed in fixed doses: lisinopril – 10 mg, hydrochlorothiazide – 12.5 mg. The effectiveness of treatment was assessed at 3-4 weeks of treatment. In the absence of a targeted reduction in blood pressure, the dose of lisinopril was doubled, i.e., Co-Diroton was prescribed in the ratio of dosages of lisinopril and hydrochlorothiazide – 20/12.5 mg. The effectiveness of treatment was assessed using QSMADD according to the dynamics of TDS.
Figure 2 shows the dynamics of TDS indicators during monotherapy with lisinopril and the use of a fixed combination of lisinopril with hydrochlorothiazide. As a result of monotherapy with lisinopril, there was a slight decrease in blood pressure, but it was insufficient and was accompanied by a decrease in diuresis in the morning and evening.
Against the background of the use of a fixed combination of lisinopril with hydrochlorothiazide, there was an additional decrease in blood pressure, an increase in daytime diuresis and a decrease in nighttime diuresis (Fig. 2). The revealed dynamics of blood pressure and diuresis makes it possible to explain the achieved antihypertensive effect by restoring the circadian water and electrolyte balance. The target reduction in blood pressure was achieved in 12 out of 15 patients, and in 3 cases it was required to use Co-Diroton with a fixed dose of lisinopril 20 mg, in 3 cases – a calcium channel blocker – amlodipine at a dose of 2.5 mg. The treatment was well tolerated by patients, and only in one case was a transient appearance of coughing, which passed on its own without discontinuation of the drug. Our study allowed us to give a positive assessment of the therapeutic efficacy of the fixed combination of lisinopril with hydrochlorothiazide (Co-Diroton), to determine the list of clinical situations in which the use of this drug will have certain advantages. The latter include:
• advanced age of patients;
• smoking, physical inactivity, overweight and other risk factors that contribute to fluid retention in the body;
• insufficient effect of monotherapy with an ACE inhibitor;
• increase in blood pressure against the background of a decrease in daily diuresis;
• lack of nightly decrease in blood pressure;
• the presence of microalbuminuria and other signs of nephropathy;
• the presence of heart failure;
• meteorological instability with sharp fluctuations in atmospheric pressure.
The use of the fixed combination of lisinopril with hydrochlorothiazide should be limited during periods of extremely hot weather and in other cases, accompanied by a significant loss of fluid and electrolytes. In these situations, the significance of diuresis testing is greatly reduced, and measurement of the patient’s weight should be used to assess fluid balance.
The antihypertensive effect of the fixed combination of lisinopril with hydrochlorothiazide can be enhanced by the additional administration of the calcium channel blocker amlodipine.

Literature
1. 2007 recommendations for the treatment of arterial hypertension. Rational Pharmacotherapy in Cardiology 2008;(1–2):2–76
2. Mukhin N.A., Moiseev B.C., Kobalava Zh.D. Cardiorenal interactions: clinical significance and role in the pathogenesis of diseases of the cardiovascular system and kidneys. Ter archive 2004; 6:39–46
3. Opie LH. Angiotensin–converting enzyme inhibitors: scientific basis for clinical use. John Wiley & Sons: New York, 1992.
4. Jaiani N.A. Cardioprotective and nephroprotective effects of angiotensin-converting enzyme inhibitors. Russian medical journal. 2005; 27: 1858–1863
5. Kutishenko N.P., Martsevich S.Yu. Angiotensin-converting enzyme inhibitor lisinopril: features of use in cardiology. Atmosphere 2007;(2):2–5.
6. Savenkov M.P., Ivanov S.N., Botsoeva M.A., Mikhailusova M.P. Correction of high blood pressure in the morning with ACE inhibitors. Gedeon Richter in the CIS 2001;4(8):27–30.
7. Kislyak O.A. ACE inhibitor lisinopril in the treatment of elderly patients with isolated systolic and systolic-diastolic arterial hypertension. Medical business 2007;(2):2–7.
8. Oshchepkova E.V. Possibilities of the angiotensin-converting enzyme inhibitor lisinopril (Diroton) in the treatment of patients with arterial hypertension with concomitant liver pathology. Atmosfera.Kardiology 2007;(3):1–4.
9. Savenkov M.P., Kirichenko A.V., Ivanov S.N. , et al. Seasonal adjustment of antihypertensive therapy. Consilium Medicum.2008, v.10, no.5 p.17–20
10. Kobalava, Zh. D. Treatment of arterial hypertension: diuretics. Russian medical journal. 2000; Volume 8, No. 4, p. 15–18.
11. Kobalava Zh.D., Villevalde S.V. Diuretics are the cornerstone of modern antihypertensive therapy. Consilim medicum. v. 11 Vol. No. 4, p. 24–27
12. 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 349patients with mild to moderate tssential hypertension. J. Cardiovasc. Pharmacol. 1987 9(suppl.3) S 36–54
13. Leduc J.J., Madonna O., Grossin V. Evaluation of lisinopril–hydrochlorthizide combination in mild to moderate hypertension. Therapie 1994 49(1) 17–22
14. 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
15. Savenkov M.P., Kirichenko A.V., Borshchevskaya M.V., Ivanov S.N. Individual selection of diuretic therapy using combined monitoring of diuresis and blood pressure in patients with arterial hypertension and heart failure. Russian journal of cardiology. 2009; No. 6, pp. 19–24.

Akrikhin – instructions for use, dosage, composition, analogs, side effects / Pillintrip

Symptomatic hypotension

Symptomatic hypotension is rarely observed in uncomplicated hypertensive patients, but is more likely to occur if the patient is debilitated, for example. diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting, or severe renin-dependent hypertension. Regular determination of serum electrolytes should be carried out at appropriate intervals in such patients. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustments should be monitored under close medical supervision. Particular attention is paid 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 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. After restoration of effective blood volume and pressure, it may be possible to restore therapy at a reduced dosage; or any of the components can be used properly separately.

In some patients with heart failure who have normal or low blood pressure, an additional reduction in systemic blood pressure may occur 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.

Stenosis of the aortic and mitral valves / Hypertrophic cardiomyopathy

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

Double 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, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.

If dual block therapy is considered absolutely necessary, this should only be done 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.

Renal function impairment

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

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

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

Some patients with bilateral renal artery stenosis or arterial stenosis in a solitary kidney treated with ACE inhibitors have experienced increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy. This is especially likely in patients with renal insufficiency. In the presence of 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 be a contributing factor to the above, renal function should be monitored during the first few 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 given concomitantly with a diuretic.

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

Diuretic pretreatment

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

Kidney transplantation

Should not be used as there is no experience with recent kidney transplant patients.

Anaphylactoid reactions in hemodialytic 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) apheresis with dextran sulfate) and treated concomitantly with an ACE inhibitor. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

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

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

Hepatic insufficiency

Thiazides should be used with caution in patients with impaired hepatic function or advanced liver disease, as minor changes in fluid and electrolyte balance may precipitate 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 who develop jaundice or a marked increase in liver enzymes should discontinue lisinopril/hydrochlorothiazide and receive appropriate medical supervision.

Surgery / Anesthesia

In patients undergoing major surgery or during anesthesia with drugs that cause hypotension, lisinopril may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is thought to be due to this mechanism, it can be corrected by volume expansion.

Metabolic and endocrine effects

ACE inhibitor and thiazide therapy may impair glucose tolerance. It may be necessary to adjust the dosage of antidiabetic agents, including insulin. In diabetic patients receiving oral antidiabetic agents or insulin, glycemic levels should be closely monitored during the first month of treatment with an ACE inhibitor. 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 uric acid and thus may weaken the hyperuricemic effect of hydrochlorothiazide.

Electrolyte imbalance

For any patient receiving diuretic therapy, periodic determination of serum electrolytes should be carried out at appropriate intervals.

Thiazides, including hydrochlorothiazide, may cause fluid or electrolyte imbalances (hypokalemia, hyponatremia, and hypochloremic alkalosis). Warning signs of fluid or electrolyte imbalance are dry mouth, thirst, weakness, lethargy, drowsiness, muscle pain or cramps, muscle fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting. Dilutional hyponatremia may occur in edematous patients during hot weather. Chloride 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 may cause intermittent and slight elevations in serum calcium levels. Marked hypercalcemia may be evidence of latent hyperparathyroidism. Thiazides should be discontinued prior to testing for parathyroid function.

Hyperkalemia

Increased serum potassium levels have 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 using concomitant potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes, or those taking other drugs associated with an increase in serum potassium levels (eg, heparin, trimethoprim/sulfamethoxazole combination, also known as cotrimoxazole). If the concomitant use of the above agents is considered appropriate, regular monitoring of serum potassium levels is recommended.

Patients with diabetes

In diabetic patients receiving oral antidiabetic agents or insulin, glycemic control should be closely monitored during the first month of treatment with an ACE inhibitor.

Hypersensitivity/angioedema

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely 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 should be carried out to ensure complete resolution of symptoms before the patient is discharged. Even in cases where only the tongue edema occurs, long-term follow-up may be required without respiratory distress, as treatment with antihistamines and corticosteroids may not be sufficient.

Very rare deaths due to angioedema associated with laryngeal or tongue edema have been reported. 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 treatment should be carried out immediately. This may include administering adrenaline and/or maintaining a patent airway. The patient should be under close medical supervision until complete and sustained resolution of symptoms.

ACE inhibitors cause a higher incidence 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 taking an ACE inhibitor.

Patients taking concomitant mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus therapy may be at increased risk of angioedema (eg, swelling of the airways or tongue, with or without respiratory failure).

In patients receiving thiazides, hypersensitivity reactions may occur with or without a history of allergy or asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides.

Desensitization

Patients receiving ACE inhibitors during desensitization treatment (eg hymenoptera venom) have sustained anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but reappeared on inadvertent recall.

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 other complicating factors. Neutropenia and agranulocytosis are reversible upon discontinuation of the ACE inhibitor. Lisinopril should be used with extreme caution in patients with collagen vascular disease, immunosuppressive therapy, allopurinol or procainamide treatment, or a combination of these complicating factors, especially in the presence of pre-existing impaired renal function. Some of these patients developed serious infections, which in some cases did not respond to intensive antibiotic therapy. If lisinopril is used in such patients, periodic monitoring of the white blood cell count is recommended and patients should be instructed to report any signs of infection.

Race

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

As with other ACE inhibitors, lisinopril may be less effective in lowering blood pressure in black patients than in non-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. Characteristically, the cough is unproductive, persistent, and disappears after cessation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

Lithium

The combination of an ACE inhibitor and lithium is not generally recommended.