Prescription medication · Thiazide Diuretic / ACE Inhibitor Combination
hydrochlorothiazide/lisinopril
Also sold as Zestoretic. Zestoretic is used to treat high blood pressure.
Data updated 2026-05-15
- 75,364
- FDA reports
- 13
- InteractionsSeveral interactions
- Rx
- Availability
What the data shows
hydrochlorothiazide/lisinopril (Zestoretic) is a prescription Thiazide Diuretic / ACE Inhibitor Combination, with 75,364 FDA adverse-event reports on file, with 13 documented drug interactions.
Reporting volume reflects how widely a drug is used and studied, not how dangerous it is, a FAERS report documents a temporal association, never proof of cause.
hydrochlorothiazide/lisinopril (Zestoretic) is a prescription Thiazide Diuretic / ACE Inhibitor Combination. Zestoretic is used to treat high blood pressure.
Zestoretic is a drug that combines lisinopril and hydrochlorothiazide. It is used to treat high blood pressure.
Verify with FDA → · CMS NADAC pricing →
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.
The sections below are summarized in plain English from hydrochlorothiazide/lisinopril's FDA-approved prescribing information. They describe what the official label says, and are not personal medical advice.
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.
Side Effects (from patient reports)
Based on 75,364 FDA adverse event reports.
Most-reported reactions
Adverse reactions in FAERS for hydrochlorothiazide/lisinopril, by number of reports
- Feeling tired
Feeling tired
10,013 reports
- Feeling sick to your stomach
Feeling sick to your stomach
9,706 reports
- Loose stools
Loose stools
8,311 reports
- Discomfort
Discomfort
7,665 reports
- Difficulty breathing
Difficulty breathing
7,584 reports
- Head pain
Head pain
7,516 reports
- Feeling lightheaded
Feeling lightheaded
7,310 reports
- Joint pain
Joint pain
6,080 reports
- Weakness
Weakness
5,629 reports
- Accidental fall
Accidental fall
5,550 reports
What this shows Bars show how often each reaction was reported, not how likely it is to happen, a report records a temporal association, never proof that the drug caused it.
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.
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...
Mechanism: Taking these medicines together can cause your blood pressure to drop to an unsafe level, especially when you first start the treatment.
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...
Mechanism: Combining these two drugs can cause your potassium levels to rise and may lead to serious kidney problems without providing extra benefits.
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.
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.
This is a plain-language summary of FDA-label interaction records and does not provide individual medication-combination directions.
Common Questions
Can I take Zestoretic if I am allergic to sulfa drugs?
Can I take Zestoretic if I have diabetes?
What should I do if I feel dizzy after taking Zestoretic?
Can I take Zestoretic with potassium supplements?
How long will I need to take Zestoretic?
Can Zestoretic cause kidney problems?
Can Zestoretic interact with other medications?
What are the symptoms of angioedema?
Can I drink alcohol while taking Zestoretic?
How quickly does Zestoretic start working?
What are the common side effects of hydrochlorothiazide/lisinopril?
Does hydrochlorothiazide/lisinopril interact with other medications?
What drug class is hydrochlorothiazide/lisinopril?
What pregnancy or breastfeeding source fields are listed for hydrochlorothiazide/lisinopril?
Related Medications in Thiazide Diuretic / ACE Inhibitor Combination
Other drugs grouped near hydrochlorothiazide/lisinopril - same-class peers and common alternatives.
acebutolol
Sectral
Acebutolol is a medicine that helps lower blood pressure and control irregular heartbeats.
Compare with hydrochlorothiazide/lisinopril →
aliskiren
Tekturna
Tekturna is a medicine used to treat high blood pressure.
Compare with hydrochlorothiazide/lisinopril →
amiloride
Midamor
Amiloride is a water pill that helps your body hold onto potassium.
Compare with hydrochlorothiazide/lisinopril →
amlodipine
Norvasc
Amlodipine (Norvasc) is a drug that lowers blood pressure and treats chest pain.
Compare with hydrochlorothiazide/lisinopril →
amlodipine/benazepril
Lotrel
Lotrel is a combination medicine that contains amlodipine and benazepril.
Compare with hydrochlorothiazide/lisinopril →
Compare hydrochlorothiazide/lisinopril vs acebutolol side-by-side →
Medication Guides
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FDA bioequivalence and label-record context for narrow therapeutic index medicines
Common Drug Interactions
Dangerous medication combinations and how to protect yourself
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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 75,364 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 are separate source-record fields. This page is a public FDA/CMS registry and does not provide medical, treatment, substitution, or medication-change directions.
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. This registry does not provide medication decisions.
Last updated: March 31, 2025
PlainMeds is rendered directly from FDA openFDA/FAERS extracts, DailyMed labels, and CMS drug-pricing files, no number is typed in by an editor. FAERS counts, recalls, shortages, and price figures on this page are queried live from those federal extracts. See our editorial standards & corrections policy, the methodology behind these numbers, or report a data error. Data current as of 2026-05-15. Primary sources: openFDA / FAERS, DailyMed and CMS Part B ASP.
Read our methodology - how this data is sourced, computed, and verified.
Data currency: FDA FAERS adverse-event reports through 2025, CMS NADAC acquisition-cost pricing effective December 2024, compiled from the source snapshot dated . See our methodology for per-source dates and refresh cadence. Spot a figure that looks wrong? Report a data issue.
All federal data sources used on this page
- FDA Orange Book - approved drug products with therapeutic equivalence. accessdata.fda.gov/cder/ob
- FDA DailyMed - NIH-hosted drug labeling for FDA-approved meds. dailymed.nlm.nih.gov
- FDA Adverse Event Reporting System (FAERS) - post-marketing safety surveillance. fda.gov/drugs/faers
- NLM RxNorm - standardized clinical drug nomenclature. nlm.nih.gov/research/umls/rxnorm
- CMS Medicare Part B Drug Average Sales Price Files - federal drug pricing data. cms.gov/medicare/part-b-drugs/asp
- FDA Drug Shortages Database - current and resolved drug shortage tracking. accessdata.fda.gov/drugshortages