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hydrochlorothiazide/lisinopril

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Brand names: Zestoretic

Thiazide Diuretic / ACE Inhibitor Combination Rx

Zestoretic is a drug that combines lisinopril and hydrochlorothiazide. It is used to treat high blood pressure.

What it does

Zestoretic is used to treat high blood pressure.

Common side effects

Dizziness, Headache, Cough

Key warnings

This drug can cause serious harm or death to an unborn baby.

How It Works

Zestoretic contains two medicines. Lisinopril is an ACE inhibitor that widens blood vessels. Hydrochlorothiazide is a diuretic that helps your body get rid of extra salt and water, which also lowers blood pressure.

How to Take It

Take Zestoretic exactly as your doctor tells you. Your doctor may change your dose over time to find what works best. You can take this medicine with or without food. Try to take it at the same time each day.

Pregnancy & Breastfeeding

Do not take Zestoretic if you are pregnant. It can harm your unborn baby. Talk to your doctor about other blood pressure medicines if you are breastfeeding.

Missed Dose

If you miss a dose, take it as soon as you remember. If it is close to your next dose, skip the missed dose and continue with your regular schedule.

Storage

Store Zestoretic at room temperature, away from light and moisture.

Side Effects (from patient reports)

Based on 79,221 FDA adverse event reports.

Feeling tired
10,013
Feeling sick to your stomach
9,706
The medicine is not working
9,356
Loose stools
8,311
Discomfort
7,665
Difficulty breathing
7,584
Head pain
7,516
Feeling lightheaded
7,310
Joint pain
6,080
Using the medicine for something it is not approved for
5,680

Serious Warnings

This drug can cause serious harm or death to an unborn baby. Stop taking Zestoretic as soon as you find out you are pregnant.

Known Drug Interactions

Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Do not co-administer aliskiren with ZESTORETIC in patients with diabetes. Avoid use of aliskiren with ZESTORETIC in patients with renal impairment (GFR < 60 mL/min).

Mechanism: Combining these medications puts too much stress on the system that regulates blood pressure, increasing the risk of fainting and kidney damage.

What to do: Do not use these drugs together if you have diabetes, and your doctor should check your kidney function and potassium levels closely.

Drug Interactions Lisinopril Hypotension - Patients on Diuretic Therapy: Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with lisinopril. The possibility of hypotensive effects with lisinopril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with lisinopril. If it is necessary to continue the diuretic, initiate therapy with lisinopril at a dose of 5 mg daily, and provide close medical...

Mechanism: Taking these medicines together can cause your blood pressure to drop to an unsafe level, especially when you first start the treatment.

What to do: Your doctor may need to adjust your salt intake or change your dose to prevent your blood pressure from falling too low.

The VA NEPHRON trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 mL/min to 89.9 mL/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years. Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end state renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney inju...

Mechanism: Combining these two drugs can cause your potassium levels to rise and may lead to serious kidney problems without providing extra benefits.

What to do: Your doctor will likely avoid this combination or monitor your kidney function and blood levels very closely.

No meaningful clinically important pharmacokinetic interactions occurred when lisinopril was used concomitantly with propranolol, digoxin, or hydrochlorothiazide. Hydrochlorothiazide When administered concurrently the following drugs may interact with thiazide diuretics. Cholestyramine and colestipol resins - Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.

Mechanism: There are no major negative interactions when these two medicines are used together, and they are often found in the same pill.

What to do: You can continue taking these medicines together as directed by your healthcare provider.

Use of lisinopril with potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium.

Mechanism: Both of these medicines can cause your body to keep too much potassium, which can lead to dangerously high levels in your blood.

What to do: Your doctor will need to perform regular blood tests to check your potassium levels while you take these drugs.

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Common Questions

Can I take Zestoretic if I am allergic to sulfa drugs?
You should not take Zestoretic if you are allergic to sulfa drugs.
Can I take Zestoretic if I have diabetes?
Do not take Zestoretic with aliskiren if you have diabetes.
What should I do if I feel dizzy after taking Zestoretic?
Lie down until the dizziness passes. Talk to your doctor if dizziness continues.
Can I take Zestoretic with potassium supplements?
Talk to your doctor before taking potassium supplements with Zestoretic.
How long will I need to take Zestoretic?
You may need to take Zestoretic for a long time to control your blood pressure. Talk to your doctor.
Can Zestoretic cause kidney problems?
Zestoretic can cause kidney problems, especially if you also take NSAIDs. Your doctor will monitor your kidney function.
Can Zestoretic interact with other medications?
Yes, Zestoretic can interact with other medications. Tell your doctor about all the medicines you take.
What are the symptoms of angioedema?
Symptoms of angioedema include swelling of the face, lips, tongue, or throat.
Can I drink alcohol while taking Zestoretic?
Talk to your doctor about drinking alcohol while taking Zestoretic.
How quickly does Zestoretic start working?
Zestoretic starts working within a few hours, but it may take several weeks to see the full effect.
What are the common side effects of hydrochlorothiazide/lisinopril?
The most commonly reported side effects of hydrochlorothiazide/lisinopril include Dizziness, Headache, Cough, Feeling tired. Based on 79,221 FDA adverse event reports. Always consult your healthcare provider about potential side effects.
Does hydrochlorothiazide/lisinopril interact with other medications?
Yes, hydrochlorothiazide/lisinopril has 13 known drug interactions. Notable interactions include aliskiren, lisinopril, losartan. Always inform your doctor about all medications you are taking.
What drug class is hydrochlorothiazide/lisinopril?
hydrochlorothiazide/lisinopril belongs to the Thiazide Diuretic / ACE Inhibitor Combination drug class. It requires a prescription (Rx). Zestoretic is used to treat high blood pressure.
Is hydrochlorothiazide/lisinopril safe during pregnancy?
Do not take Zestoretic if you are pregnant. It can harm your unborn baby. Always consult your healthcare provider before using any medication during pregnancy or breastfeeding.

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Related Health & Safety Data

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What the FDA Data Shows for hydrochlorothiazide/lisinopril

The FDA label for hydrochlorothiazide/lisinopril (sold under brand names such as Zestoretic) classifies it as a prescription-only medication in the Thiazide Diuretic / ACE Inhibitor Combination class. Zestoretic is used to treat high blood pressure. Official labeling lists 4 commonly reported side effects, including Dizziness, Headache, Cough.

Post-market surveillance from the FDA Adverse Event Reporting System (FAERS) captures real-world experience. For this drug, FAERS contains 79,221 voluntary reports. The database also lists 13 documented drug interactions derived from FDA labeling, with the top-flagged interaction rated major severity. Acquisition-cost data is surveyed weekly by CMS and updated as manufacturers report changes.

Report counts do not establish causation — a FAERS entry documents a temporal association, not proof that the drug produced the outcome. Widely prescribed medications naturally accumulate more reports than niche therapies, so raw totals must be interpreted alongside total exposure. Shortage status, recall history, and patent information further shape supply and switching decisions. This page summarizes public FDA data for educational purposes only and is not a substitute for professional medical advice — always consult a licensed healthcare provider before starting, stopping, or changing any medication.

Data Sources

Drug labeling: FDA Drug Labels (SPL/DailyMed). Adverse events: FDA Adverse Event Reporting System (FAERS).

FAERS reports are voluntary and do not establish causation. Drug interactions are derived from FDA labeling and clinical references. Always consult a healthcare professional before making medication decisions.

Last updated: March 31, 2025

All federal data sources used on this page