What are the key benefits of lisinopril-HCTZ for hypertension management. How does this combination drug work to lower blood pressure effectively. What are the potential side effects and precautions associated with lisinopril-HCTZ use. How can patients optimize their treatment with this medication for better cardiovascular health.

Understanding Lisinopril-HCTZ: A Potent Combination for Blood Pressure Control

Lisinopril-HCTZ is a powerful combination medication used to treat hypertension, or high blood pressure. This drug combines two active ingredients: lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (HCTZ), a diuretic. By working together, these components provide a synergistic effect in managing blood pressure levels more effectively than either medication alone.

The brand name for this combination drug is Zestoretic, although it’s also available as a generic medication. Typically prescribed when a single medication proves insufficient for blood pressure control, lisinopril-HCTZ offers a comprehensive approach to hypertension management.

How Does Lisinopril-HCTZ Work?

The mechanism of action for lisinopril-HCTZ involves two distinct processes:

• Lisinopril relaxes blood vessels, reducing the workload on the heart and lowering blood pressure.
• Hydrochlorothiazide acts as a diuretic, helping the body eliminate excess salt and water, which further contributes to blood pressure reduction.

This dual-action approach makes lisinopril-HCTZ particularly effective in managing hypertension, especially in cases where monotherapy has proven inadequate.

The Benefits and Indications of Lisinopril-HCTZ Treatment

Lisinopril-HCTZ offers several advantages in the treatment of hypertension. Its primary indication is for patients whose blood pressure is not adequately controlled by lisinopril or hydrochlorothiazide alone. The combination of these two medications in a single tablet can improve patient compliance and provide more consistent blood pressure control.

Is lisinopril-HCTZ suitable for all hypertensive patients. While it’s effective for many, it’s not appropriate for everyone. Patients with a history of angioedema, those who are pregnant, or individuals with certain kidney conditions may not be suitable candidates for this medication. Always consult with a healthcare provider to determine the most appropriate treatment plan.

Additional Benefits of Lisinopril-HCTZ

• Reduced risk of cardiovascular events
• Potential for improved outcomes in heart failure patients
• Protection against kidney damage in diabetic patients
• Once-daily dosing for improved convenience

Potential Side Effects and Safety Considerations

As with any medication, lisinopril-HCTZ can cause side effects. While many patients tolerate the drug well, it’s crucial to be aware of potential adverse reactions.

Common Side Effects

Common side effects of lisinopril-HCTZ may include:

• Dizziness
• Headache
• Persistent cough
• Fatigue
• Orthostatic hypotension (low blood pressure when standing up)

These side effects are often mild and may resolve on their own as the body adjusts to the medication. However, if they persist or worsen, it’s important to consult with a healthcare provider.

Serious Side Effects and Warnings

While less common, serious side effects can occur with lisinopril-HCTZ use. These may include:

1. Allergic reactions (including angioedema)
2. Severe hypotension
3. Liver failure
4. Electrolyte imbalances
5. Kidney problems

Do the benefits of lisinopril-HCTZ outweigh the risks. For most patients with hypertension, the answer is yes. However, individual risk factors and medical history must be carefully considered. Regular monitoring and follow-up with a healthcare provider are essential to ensure the medication’s safety and efficacy.

The FDA Black Box Warning: Pregnancy and Lisinopril-HCTZ

One of the most critical safety considerations for lisinopril-HCTZ is its contraindication during pregnancy. The FDA has issued a black box warning, the most serious type of warning, regarding the use of this medication in pregnant women.

Using lisinopril-HCTZ during pregnancy can cause fetal harm and even death. Women who become pregnant while taking this medication should discontinue use immediately and consult their healthcare provider. Alternative antihypertensive treatments that are safe for use during pregnancy should be considered.

Pregnancy and Hypertension Management

For women of childbearing age who require blood pressure management:

• Discuss family planning with your healthcare provider before starting lisinopril-HCTZ
• Use effective contraception while taking this medication
• Have a plan in place for switching to pregnancy-safe alternatives if conception occurs
• Regular pregnancy tests may be recommended for women at risk of pregnancy

Optimizing Treatment with Lisinopril-HCTZ

To maximize the benefits of lisinopril-HCTZ while minimizing risks, patients should follow their healthcare provider’s instructions carefully. Here are some tips for optimizing treatment:

1. Take the medication at the same time each day to maintain consistent blood levels
2. Do not skip doses or stop taking the medication without consulting your doctor
3. Monitor your blood pressure regularly and keep a log to share with your healthcare provider
4. Be aware of potential drug interactions and inform your doctor of all medications you’re taking
5. Maintain a healthy lifestyle, including a balanced diet and regular exercise, to support the medication’s effects

Can lifestyle changes enhance the effectiveness of lisinopril-HCTZ. Absolutely. Adopting a low-sodium diet, engaging in regular physical activity, maintaining a healthy weight, and limiting alcohol consumption can all contribute to better blood pressure control when combined with medication.

Drug Interactions and Precautions

Lisinopril-HCTZ can interact with various medications, supplements, and even certain foods. Understanding these interactions is crucial for safe and effective treatment.

Common Drug Interactions

• NSAIDs (e.g., ibuprofen, naproxen): May reduce the blood pressure-lowering effects
• Potassium supplements: Can lead to hyperkalemia
• Lithium: May increase lithium levels in the blood
• Diabetes medications: May require dose adjustments due to blood sugar effects
• Other blood pressure medications: Can potentiate hypotensive effects

Are there dietary considerations when taking lisinopril-HCTZ. Yes, patients should be cautious with salt substitutes containing potassium and should discuss their diet with their healthcare provider. Alcohol consumption should be limited, as it can enhance the blood pressure-lowering effect of the medication and increase the risk of orthostatic hypotension.

Monitoring and Follow-up: Ensuring Safe and Effective Treatment

Regular monitoring is essential for patients taking lisinopril-HCTZ. This includes:

1. Blood pressure checks
2. Kidney function tests
3. Electrolyte level monitoring
4. Liver function tests

How often should patients have follow-up appointments? Initially, more frequent visits may be necessary to adjust the dosage and monitor for side effects. Once stabilized, most patients will have check-ups every 3-6 months, or as recommended by their healthcare provider.

Signs to Watch For

Patients should be aware of signs that may indicate a need for immediate medical attention:

• Swelling of the face, lips, tongue, or throat
• Difficulty breathing or swallowing
• Severe dizziness or fainting
• Jaundice (yellowing of the skin or eyes)
• Unusual fatigue or weakness
• Signs of infection (fever, chills, sore throat)

Long-term Outlook and Cardiovascular Health

Lisinopril-HCTZ, when used as part of a comprehensive treatment plan, can significantly improve long-term cardiovascular health outcomes. By effectively managing hypertension, this medication helps reduce the risk of heart attacks, strokes, and other complications associated with high blood pressure.

Can patients expect to take lisinopril-HCTZ indefinitely? For many patients with chronic hypertension, long-term use of antihypertensive medication is necessary. However, some individuals may be able to reduce or discontinue medication over time with significant lifestyle changes and under close medical supervision.

Beyond Blood Pressure: Additional Health Benefits

Research suggests that ACE inhibitors like lisinopril may offer additional health benefits beyond blood pressure control:

• Potential reduction in the progression of diabetic nephropathy
• Possible cardioprotective effects in patients with heart failure
• Potential cognitive benefits in some populations

While these effects are promising, more research is needed to fully understand the long-term impacts of lisinopril-HCTZ on overall health outcomes.

In conclusion, lisinopril-HCTZ represents a powerful tool in the management of hypertension. By combining two effective medications, it offers comprehensive blood pressure control for many patients. However, as with any medication, it’s crucial to use lisinopril-HCTZ under the guidance of a healthcare professional, adhering to prescribed dosages and monitoring protocols. With proper use and regular follow-up, this medication can play a significant role in improving cardiovascular health and reducing the risk of hypertension-related complications.

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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The choice of a fixed combination of lisinopril and hydrochlorothiazide in the treatment of arterial hypertension

Summary

The article is devoted to the problem of rational choice of a fixed combination of antihypertensive drugs. The results of our own study are presented, which made it possible to give a positive assessment of the therapeutic efficacy of the fixed combination of lisinopril with hydrochlorothiazide (Co-Diroton) and to determine a list of clinical situations in which the use of this drug will have certain advantages.

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 angiotensin converting enzyme (ACE) inhibitor with a thiazide diuretic [2]. However, the combination of an ACE inhibitor with a calcium channel blocker (CCB), a CCB with a β-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 their choice 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 with their help 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) action due to a decrease in the formation of angiotensin II, are most widely used in practice to reduce high blood pressure (BP). 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 occupied by lisinopril is 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 diseases 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 the preparation Diroton ^® of the company Gedeon Richter, Hungary. Our many years of experience in the use of lisinopril (Diroton) indicates that, when monotherapy, the drug can effectively control blood pressure mainly at the initial stages of the formation of hypertension, in patients with a low and moderate risk of developing cardiovascular complications (CVS), 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 and kidney dysfunction, 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 associated with possible ACE-induced renal dysfunction (the action blocks the diuretic) and secondary activation of the synthesis of angiotensin II by the diuretic (the action blocks lisinopril). 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 clinical experience has made it possible to formulate two basic rules for the use of diuretics : these drugs should be prescribed only in the presence of fluid and electrolyte disturbances 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 thiazide diuretics is not completely excluded, which 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 patient adherence 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 of 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, the fixed combination of lisinopril with hydrochlorothiazide in doses of 10/12.5 and 20/12.5 mg is registered under the trade name Co-Diroto n 900 72 ^® (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 daily 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 as 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.BP syst. mm Hg/diuresis%). In healthy individuals, normal TDS values ​​range from 120–135 mm Hg. Art./ 75–100%. TDS allows you to determine the relationship between blood pressure and diuresis at different times of the day.

The experience of using XMADD in more than 200 patients with cardiovascular pathology indicates that the TDS value can be used to evaluate the effectiveness of treatment for hypertension, including a thiazide diuretic, according to the dynamics of diuresis (Fig. 1). The study during the QSMAD diuresis revealed the presence of daytime fluid retention in patients with hypertension, followed by its more intense release at night (see Fig. 1). Activation of nocturnal diuresis in patients occurred against the background of elevated blood pressure.

The revealed relationships between diuresis and blood pressure allow us to understand the reason for the absence of a nightly 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 (see Fig. 1). The use of KSMADD allows you to justify the choice and evaluate the effectiveness of the fixed combination of lisinopril with hydrochlorothiazide.

Fig. 1

Change in daily diuresis profile in hypertensive patients treated with hydrochlorothiazide

This combination (Co-Diroton ^® , Gedeon Richter, Hungary) was used in 15 patients (11 men and 4 women) aged 56–75 years with hypertension II–III degree, with a high gradation of risk, in whom lisinopril monotherapy (Diroton ^® , Gedeon Richter, Hungary) at a daily dose of 10–20 mg, which was previously carried out for 3–4 weeks, turned out to be insufficiently effective, according to KSMADD . Out of 15 patients 9were 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 carried out 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/hour, 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 the treatment was assessed at the 3-4th week of treatment. In the absence of a targeted reduction in blood pressure, the dose of lisinopril was doubled, that is, 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.

Fig. 2

Change in the daily profile of blood pressure and diuresis (%) in patients with hypertension in mono- and combined with hydrochlorothiazide therapy with lisinopril

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 and a decrease in night diuresis (see Fig. 2). The revealed dynamics of blood pressure and diuresis allows us 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 – CCB of amlodipine at a dose of 2. 5 mg. The treatment was well tolerated by patients, and only in one case was there 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:

• elderly patients;
• smoking, physical inactivity, overweight and other risk factors that contribute to fluid retention in the body;
• insufficient effect of ACE inhibitor monotherapy;
• increase in blood pressure against the background of a decrease in daily diuresis;
• no nocturnal BP drop;
• the presence of microalbuminuria and other signs of nephropathy;
• presence of heart failure;
• meteorological instability with sharp fluctuations in atmospheric pressure.

The use of lisinopril with hydrochlorothiazide fixed combination should be limited during periods of extremely hot weather and in other cases, accompanied by 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 CCB amlodipine.

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