Zestoretic (Lisinopril and Hydrochlorothiazide) - Oral

Warning:

Taking Zestoretic (lisinopril and hydrochlorothiazide) can have a negative effect on your unborn fetus. If you're pregnant or you suspect that you're pregnant, immediately let your healthcare provider know. They will help you safely stop this medication.

What Is Zestoretic?

Zestoretic (lisinopril and hydrochlorothiazide) is a prescription combination tablet that contains two different medications: lisinopril and hydrochlorothiazide (HCTZ). Both of these medications can be used to treat hypertension (high blood pressure).

Lisinopril is an angiotensin converting enzyme (ACE) inhibitor (blocker). Blocking the ACE protein results in lower angiotensin II hormone levels in your body. This relaxes your blood vessels which in turn lowers your blood pressure.

HCTZ, on the other hand, is a thiazide diuretic (water pill). The medication affects a specific part of the kidneys. Diuretics lower blood pressure by causing the kidneys to make more urine (pee) to remove extra salt and water from the body.

Drug Facts

Generic Name: Lisinopril and Hydrochlorothiazide (HCTZ)

Brand Name: Zestoretic

Drug Availability: Prescription

Therapeutic Classification: ACE inhibitor and Thiazide diuretic

Available Generically: Yes

Controlled Substance: N/A

Administration Route: Oral (by mouth)

Active Ingredient: Lisinopril and HCTZ

Dosage Form: Tablet

What Is Zestoretic Used For?

Zestoretic is available as a combination tablet to treat hypertension (high blood pressure). Hypertension is a blood pressure measurement with the systolic (top number) being higher than 130 millimeters of mercury (mm Hg) or the diastolic (bottom number) being above 80 millimeters of mercury.

In the United States (U.S.), approximately 50% of adults have hypertension or are taking medications to treat high blood pressure. Only 25% of adults with hypertension, however, have well-controlled blood pressure.

Many people usually don't have any symptoms with hypertension until they have a heart attack or stroke. Uncontrolled blood pressure can raise the risk for these medical conditions, which are the leading causes of death in the U.S.

Zestoretic (Lisinopril and Hydrochlorothiazide) Drug Information - Illustration by Dennis Madamba

Verywell / Dennis Madamba

How to Take Zestoretic

Take Zesoretic once daily by mouth with or without food, as directed by your healthcare provider.

Storage

After picking Zestoretic up from the pharmacy, store the medication at room temperature between 68 degrees to 77 degrees Fahrenheit (F). Protect Zestoretic from light, and don't expose the medication to humid or moist environments.

If you're going to travel with Zestoretic, become familiar with the regulations of your final destination. In general, it's a good idea to keep your medication in its original container from the pharmacy, with your name on it.

How Long Does Zestoretic Take to Work?

You might notice Zestoretic effects within one to two hours—with lisinopril starting to work within one hour and HCTZ beginning to work within two hours.

What Are the Side Effects of Zestoretic?

Side effects are possible with Zestoretic.

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your pharmacist or a healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 1-800-FDA-1088.

Common Side Effects

Common side effects with Zestoretic include:

Severe Side Effects

Severe side effects are possible with Zestoretic. Get medical help right away if you experience the following side effects:

  • Abnormal amounts of white blood cells (WBCs): ACE inhibitors might be linked to abnormal amounts of WBCs. WBCs help fight off infections. Contact your healthcare provider if you're experiencing symptoms of an infection (e.g., sore throat or fever).
  • Abnormal amounts of potassium: Lisinopril can cause high potassium levels with symptoms of nausea, vomiting, abnormal heart rate and chest pain. HCTZ, on the other hand, can cause low potassium levels with symptoms of abnormal heart rate, muscle spasms, and tingly or numb sensation.
  • Severe allergic reaction or anaphylaxis-like reactions: Symptoms of a severe allergic reaction or anaphylaxis-like reactions may include rash, itchiness, swelling and breathing difficulties.
  • Angioedema: Lisinopril may cause swelling of the face, eyes, lips, and tongue (angioedema). You may also have trouble breathing.
  • Excessively low blood pressure: While low blood pressure is a common side effect of Zestoretic, it can be excessive and severe. If you're experiencing dangerously low blood pressure, symptoms may include lightheadedness and fainting spells.
  • Glaucoma: HCTZ can cause glaucoma (high pressure in the eye). Symptoms may include vision changes and eye pain.
  • Gout: HCTZ is linked to a higher risk of gout (a type of arthritis). Symptoms may include severe pain, redness and swelling in the joints—typically in the big toe.
  • Liver failure: Liver failure is a rare but serious side effect of lisinopril. Symptoms may include dark urine, upper right-sided stomach pain, nausea, vomiting, and jaundice (yellowing of skin or eyes).
  • Skin cancer: HCTZ can cause your skin to be sensitive to the sun. Protect your skin from the sun. Use sunscreen (at least SPF 30) and wear protective clothing when outdoors. Avoid tanning booths and sunlamps.
  • Systemic lupus erythematosus (SLE): There are reports linking HCTZ to new or worsening SLE. In SLE, the immune system attacks different parts of your body by mistake. Symptoms may include a butterfly rash on your face, severe tiredness, and joint pain or swelling.

Long-Term Side Effects

Long-term use of Zestoretic may raise your risk for low potassium because of HCTZ.

Report Side Effects

Zestoretic may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your healthcare provider may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting Program or call the FDA by phone (800-332-1088).

Dosage: How Much Zestoretic Should I Take?

Drug Content Provided and Reviewed by IBM Micromedex®

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For high blood pressure:
      • Adults—At first, 10 milligrams (mg) lisinopril and 12.5 mg hydrochlorothiazide once a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 80 mg lisinopril and 50 mg hydrochlorothiazide per day.
      • Children—Use and dose must be determined by your doctor.

Modifications

Your healthcare provider might slightly change your Zestoretic treatment or other medications under the following situations:

People who identify as Black: For lowering blood pressure, lisinopril might be less effective in Black individuals.

People with diabetes: Lisinopril may lower your blood sugar, but HCTZ may raise your blood sugar levels. If necessary, your healthcare provider can help you adjust your diabetes medications.

People with kidney problems: If you have kidney problems, you may have a higher risk of side effects from Zestoretic. Your healthcare provider will closely monitor and adjust your Zestoretic dose as necessary.

People with liver problems: If you have liver problems, you'll have a higher likelihood of developing side effects. Your healthcare provider will closely monitor and adjust your Zestoretic dose as necessary.

Pregnant parents: Discontinue as soon as possible when pregnancy is detected. Lisinopril can cause negative effects on the unborn fetus. Therefore, avoid Zestoretic during pregnancy.

Nursing parents: Presently, there is no effectiveness or safety information about lisinopril on nursing babies. As for HCTZ, nursing parents can take daily HCTZ doses of 50 milligrams (mg) or less. Higher HCTZ doses might negatively affect milk production. However, just because HCTZ can be taken at this time, does not mean that Zestoretic should be taken. Talk with your healthcare provider to weigh the benefits and risks of taking Zestoretic while nursing.

Missed Dose

If you accidentally forgot your Zestoretic dose, try to take it as soon as you remember. If it's already close to your next scheduled dose, however, simply skip your missed dose and take your following dose at your next scheduled time. Don't try to double up to make up for the missed dose.

Try to find ways to consistently remember to take your medication. Missing too many Zestoretic doses may lead to uncontrolled blood pressure and a higher risk of heart attack or stroke.

Overdose: What Happens If I Take Too Much Zestoretic?

If you accidentally took too many Zestoretic tablets, then you might experience the following symptoms:

  • Confusion
  • Dehydration (thirsty)
  • Dry mouth
  • Extremely low blood pressure
  • Fast heartbeat
  • Infrequent urination (pee)
  • Low amounts of different salts (e.g., potassium, sodium, and chloride)
  • Seizures
  • Vision changes

If you suspect that you're experiencing life-threatening side effects, seek immediate medical attention.

What Happens If I Overdose on Zestoretic?

If you think you or someone else may have overdosed on Zestoretic, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Zestoretic, call 911 immediately.

Precautions

Drug Content Provided and Reviewed by IBM Micromedex®

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby, especially in your second or third trimester. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using this medicine, tell your doctor right away. You may need to stop using this medicine.

You should not use this medicine together with sacubitril. Do not use this medicine and sacubitril/valsartan (Entresto®) within 36 hours of each other.

This medicine may cause a serious type of allergic reaction, including anaphylaxis, which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

Call your doctor right away if you have severe stomach pain (with or without nausea or vomiting). This could be a symptom of a condition called intestinal angioedema.

Dizziness, lightheadedness, or fainting may also occur, especially when you get up suddenly from a lying or sitting position or if you have been taking a diuretic (water pill). . If you feel dizzy, lie down so you do not faint. Then sit for a few moments before standing to prevent the dizziness from returning.

Check with your doctor right away if you become sick while taking this medicine, especially with severe or continuing nausea, vomiting, or diarrhea. These conditions may cause you to lose too much water or salt and may lead to low blood pressure. You can also lose water by sweating, so drink plenty of water during exercise or in hot weather.

This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests, or if you have any questions, check with your doctor.

Check with your doctor if you have a fever, chills, or sore throat. These could be symptoms of an infection resulting from low white blood cells.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Check with your doctor immediately if blurred vision, difficulty in reading, eye pain, or any other change in vision occurs during or after treatment. This could be a sign of a serious eye problem. Your doctor may want an eye doctor (ophthalmologist) to check your eyes.

Check with your doctor right away if you have bloody urine, a decrease in frequency or amount of urine, an increase in blood pressure, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of the face, fingers, or lower legs, trouble breathing, unusual tiredness or weakness, vomiting, or weight gain. These could be symptoms of a serious kidney problem.

Hyperkalemia (high potassium in the blood) may occur while you are using this medicine. Check with your doctor right away if you have stomach pain, confusion, irregular heartbeat, nausea or vomiting, nervousness, numbness or tingling in the hands, feet, or lips, trouble breathing, or weakness or heaviness of the legs. Ask your doctor before you use any medicine, supplement, or salt substitute that contains potassium. 

This medicine may increase your risk of getting skin cancer (eg, non-melanoma skin cancer). Avoid sun exposure. Use a sunscreen when you are outdoors. Avoid sunlamps and tanning beds. Talk to your doctor if you have concerns about this risk.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery.

This medicine may be less effective in black patients. Black patients also have an increased risk of swelling of the hands, arms, face, mouth, or throat. Talk with your doctor if you have concerns about this.

Alcohol, narcotic pain relievers, or sleeping pills may cause you to feel more lightheaded, dizzy, or faint when used with this medicine. Tell your doctor if you are drinking alcohol or using pain relievers or sleeping pills.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, and herbal or vitamin supplements.

What Are Reasons I Shouldn't Take Zestoretic?

Before taking Zestoretic, talk with your healthcare provider if the following applies to you.

  • Severe allergic reaction: If you're allergic to Zestoretic or any of its ingredients, then this combination tablet isn't an ideal choice for you.
  • Angioedema: If you have a history of angioedema, Zestoretic isn't recommended for you.
  • Pregnant parents: Lisinopril can cause negative effects on the unborn fetus. Therefore, avoid Zestoretic during pregnancy.
  • Children: There is limited effectiveness and safety information about Zestoretic in children.
  • Older adults: Some adults over 65 may have some kidney impairment; they may be at a higher risk of side effects.
  • Anuria: Anuria is when your body can't make enough urine. If you're not making any urine, HCTZ isn't a viable option for you. Therefore, Zestoretic isn't recommended.
  • Aliskiren use in people with diabetes: Aliskiren is used to treat hypertension. It lowers blood pressure in a similar way as lisinopril (an ingredient in Zestoretic). If you have diabetes, avoid combining Aliskiren and Zestoretic.
  • Neprilysin-inhibitor use: Neprilysin inhibitors prevent the neprilysin protein from breaking down other proteins called natriuretic peptides (NPs). NPs relax your blood vessels which then lowers your blood pressure. One example of a neprilysin inhibitor drug is sacubitril, which is used in a heart failure medication called Entresto. Combining a neprilysin inhibitor with lisinopril (an ingredient in Zestoretic) can raise your risk for severe swelling (angioedema).

What Other Medications Interact With Zestoretic?

Use caution when taking Zestoretic with the following medications:

  • Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs—like Advil (ibuprofen)—can lower HCTZ's effectiveness. When combined with lisinopril (an ingredient in Zestoretic), NSAIDs can also worsen kidney function. Symptoms of kidney problems may include dry or itchy skin, low energy and swollen feet.
  • Renin-angiotensin-aldosterone system (RAAS) blockers: The RAAS system contains the following three hormones: renin, angiotensin II and aldosterone. Lisinopril (an ingredient in Zestoretic) is a RAAS blocker and affects angiotensin II levels. Aliskiren, also a RAAS blocker, blocks renin. Another example of a RAAS blocker is Diovan (valsartan), which directly blocks angiotensin II. Combining RAAS blockers can increase risk of side effects.
  • Lithium: Lithium is typically used for a mental health condition called bipolar. Combining lithium with lisinopril or HCTZ (both ingredients in Zestoretic) raises the risk of lithium toxicity. Symptoms of lithium toxicity may include: slurred speech, tremors or seizures.
  • mTOR inhibitors: mTOR is an abnormal protein that's commonly found in cancer cells. mTOR inhibitors—like temsirolimus and everolimus—are typically used to treat kidney cancer. Combining mTOR inhibitors with lisinopril (an ingredient in Zestoretic), however, raises your risk of angioedema.
  • Steroids: Combining steroids with HCTZ (an ingredient in Zestoretic) can increase the likelihood of abnormal salt levels in the body—especially potassium.
  • Cholestyramine and colestipol: Cholestyramine and colestipol are treatment options for high cholesterol. These two medications can also block the absorption of HCTZ (an ingredient in Zestoretic) into the body.
  • Alcohol, barbiturates (e.g., phenobarbital for seizures) or narcotics (e.g., morphine or oxycodone for pain): Combining HCTZ (an ingredient in Zestoretic) with these medications can increase the likelihood of experiencing dangerously low blood pressure.

This isn't a complete list of medication interactions with Zestoretic. For more information about drug interactions with Zestoretic, talk with your pharmacist or healthcare provider.

What Medications Are Similar?

There are many medications that are used to treat hypertension. Zestoretic contains an ACE inhibitor and a thiazide water pill. The following medications are most similar to Zestoretic:

  • Accuretic (Quinapril and HCTZ)
  • Lotensin HCT (Benazepril and HCTZ)
  • Monopril-HCT (Fosinopril and HCTZ)
  • Uniretic (Moexipril and HCTZ)
  • Vaseretic (Enalapril and HCTZ)

There are limited clinical trials that compare different ACE inhibitors for hypertension. Studies suggest that lipophilic ("fat-loving") ACE inhibitors—like quinapril—aren't better than other ACE inhibitors.

All ACE inhibitor and HCTZ combinations are available as generic products. Many of these combos have once-daily options—with Accuretic, Uniretic, and Vaseretic giving you the choice of once or twice daily dosing. Most of these combination medicines are also available in three different strength combinations, except for Monopril-HCT and Vaseretic which have only two strength combinations.

Frequently Asked Questions

  • Will Zestoretic's side effects ever go away?

    Similar to many blood pressure medications, side effects are possible with Zestoretic. Many of the common side effects, however, are mild and temporary.


    If your side effects are bothering you, have a conversation with your healthcare provider. They can make some adjustments to lessen these side effects. If you suspect that you're having a serious or life-threatening side effect, however, get medical help right away.

  • Will I need other blood pressure medications in addition to Zestoretic?

    The number of blood pressure medications will vary per person. Some people may need more than one medication. If necessary, your healthcare provider may add another medication to further lower your blood pressure.


    If you have other heart-related medical conditions, your healthcare provider may also add other heart-related medications that can also lower your blood pressure.

  • Do I have to take Zestoretic for life?

    The duration of Zestoretic therapy will vary per person. Many people do take Zestoretic for long periods of time. With a healthy diet and exercise routine, however, some people will have well-controlled blood pressure. Some healthcare providers may agree to lower your Zestoretic dose or have a trial period without blood pressure medications depending on how you are doing.

How Can I Stay Healthy While Taking Zestoretic?

If you have hypertension (high blood pressure), make sure to regularly take your medications—like Zestoretic—to achieve well-controlled blood pressure. The following lifestyle changes are also important:

Since Zestoretic contains a water pill, also keep the following in mind.

  • Remember to take this medication in the morning. If you take it too late during the day, you might frequently wake up in the middle of the night to use the restroom.
  • Drink enough fluids throughout the day, but limit your fluid intake within two to four hours before your scheduled bedtime. This will also prevent frequent middle-of-the-night awakenings to use the restroom.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and not intended as a replacement for medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Ross Phan, PharmD, BCACP, BCGP, BCPS
Ross is a writer for Verywell with years of experience practicing pharmacy in various settings. She is also a board-certified clinical pharmacist and the founder of Off Script Consults.