Lisinopril is a prescription blood pressure drug from the angiotensin-converting enzyme (ACE) inhibitor class (the “prils”). The FDA approved it as Zestril on May 19, 1988, and Merck’s version, Prinivil, was approved a few months earlier; Prinivil is now discontinued. Lisinopril is available as a generic tablet, and it is also sold combined with hydrochlorothiazide (Zestoretic) and as an oral solution (Qbrelis).
The US label covers three uses: high blood pressure, heart failure, and lowering the risk of death after a heart attack. It carries a boxed warning for fetal toxicity. Its best-known side effects are a dry cough and, rarely, angioedema (sudden swelling of the face, tongue or throat). Lisinopril is sometimes discussed as a blood pressure option for anabolic steroid users, but no trials have tested it in that group.
This page summarizes what the FDA label and the major outcome trials report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Angiotensin-converting enzyme (ACE) inhibitor |
| Brands / approval | Zestril, NDA 019777, approved May 19, 1988; Prinivil (Merck), NDA 019558, approved December 29, 1987, now discontinued; generics |
| Route | Oral tablet; oral solution 1 mg/mL (Qbrelis) |
| Tablet strengths | 2.5, 5, 10, 20, 30 and 40 mg |
| Labeled adult hypertension dose | Start 10 mg once daily (5 mg if on a diuretic); usual range 20–40 mg once daily |
| Half-life (label) | Effective half-life ≈12 h with repeated dosing |
| Key pharmacokinetic fact | Not metabolized; excreted unchanged in urine, so dosing depends on kidney function |
| Boxed warning | Fetal toxicity: stop as soon as pregnancy is detected |
| US status | Prescription only |
| WADA status | Not named on the 2026 Prohibited List; combination tablets with hydrochlorothiazide contain a prohibited diuretic |
What it is
The label describes lisinopril as a long-acting oral ACE inhibitor and a synthetic peptide derivative, chemically (S)-1-[N2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate. Its formula is C₂₁H₃₁N₃O₅·2H₂O and its molecular weight is 441.53. It is a white to off-white powder that dissolves in water (Zestril label).
Approval records from Drugs@FDA (FDA):
| Product | Application | First approval | Status |
|---|---|---|---|
| Prinivil (Merck) | NDA 019558 | December 29, 1987 | Discontinued |
| Zestril | NDA 019777 | May 19, 1988 | Prescription |
| Zestoretic (lisinopril plus hydrochlorothiazide) | NDA 019888 | July 20, 1989 | Prescription |
| Qbrelis (oral solution, 1 mg/mL) | NDA 208401 | July 29, 2016 | Prescription |
How it lowers blood pressure
ACE converts angiotensin I into angiotensin II, a hormone that narrows blood vessels and triggers release of aldosterone (a hormone that makes the kidneys hold on to salt and water). Per the label:
- Blocking ACE lowers angiotensin II, which relaxes blood vessels and lowers aldosterone. Blood pressure falls through lower peripheral resistance, with little or no change in cardiac output or heart rate.
- Lower aldosterone can raise serum potassium slightly. In hypertensive patients with normal kidney function on lisinopril alone for up to 24 weeks, potassium rose by about 0.1 mEq/L on average, but about 15% had a rise greater than 0.5 mEq/L.
- ACE is the same enzyme as kininase, which breaks down bradykinin (a peptide that widens blood vessels). The label says it is not established whether bradykinin contributes to the drug’s effect.
- Lisinopril still lowers blood pressure in low-renin hypertension, but Black patients (more often low-renin) had a smaller average response to lisinopril alone. Adding hydrochlorothiazide removed that difference.
Onset is usually within 1 hour of a dose, with peak blood pressure lowering by about 6 hours. The effect 24 hours after dosing was present but substantially smaller than at 6 hours at all doses studied, and more consistent at 20 mg or more. Stopping abruptly was not associated with a rapid rebound in blood pressure (Zestril label).
How it differs from ARBs
Angiotensin II receptor blockers (ARBs) such as losartan and telmisartan block the angiotensin II receptor instead of the enzyme that makes angiotensin II. The losartan label notes that losartan does not affect the response to bradykinin, whereas ACE inhibitors increase it (Cozaar label). ARBs cause much less cough (see Cough below). A Cochrane review of 9 head-to-head trials (11,007 participants, at least 1 year) found no difference between ACE inhibitors and ARBs in total mortality (RR 0.98, 95% CI 0.88–1.10) or cardiovascular events (RR 1.07, 95% CI 0.96–1.19). ARBs had slightly fewer withdrawals for side effects (RR 0.83, 95% CI 0.74–0.93), mainly because of cough (Li et al., Cochrane 2014).
Pharmacokinetics
From the Zestril label (Zestril label):
| Parameter | Value |
|---|---|
| Absorption (from urinary recovery) | ≈25% on average, with wide variation (6–60%) at doses of 5–80 mg |
| Absolute bioavailability in heart failure (NYHA II–IV) | Reduced to ≈16% |
| Effect of food | None on bioavailability |
| Time to peak serum level | ≈7 h |
| Effective half-life (repeated dosing) | 12 h |
| Protein binding | Does not appear to bind serum proteins other than ACE |
| Metabolism | None |
| Elimination | Excreted unchanged, entirely in urine |
| Removed by hemodialysis | Yes |
Other label points:
- Terminal phase: blood levels show a prolonged terminal phase that probably reflects saturable binding to ACE. It does not cause accumulation.
- Kidney impairment: elimination slows, but this matters clinically only when glomerular filtration rate (GFR, a measure of kidney filtering) falls below 30 mL/min. Below that, peak and trough levels rise and steady state takes longer to reach.
- Brain: rat studies show lisinopril crosses the blood-brain barrier poorly.
- Children 6–16 years: in 29 hypertensive children, absorption was about 28% and peak levels occurred within 6 hours, similar to adults.
Approved medical use
| Indication | Labeled dosing |
|---|---|
| Hypertension, adults | Start 10 mg once daily; usual 20–40 mg once daily. Doses up to 80 mg have been used but do not appear to give greater effect. Start 5 mg if already on a diuretic |
| Hypertension, children 6 years and older (GFR over 30 mL/min/1.73 m²) | Start 0.07 mg/kg once daily (up to 5 mg); up to 0.61 mg/kg (up to 40 mg) once daily. Not recommended under 6 years or with GFR under 30 |
| Systolic heart failure (with diuretics and usually digitalis) | Start 5 mg once daily (2.5 mg if serum sodium under 130 mEq/L); increase as tolerated to 40 mg once daily |
| Acute heart attack (hemodynamically stable, within 24 h) | 5 mg, then 5 mg after 24 h, 10 mg after 48 h, then 10 mg once daily for at least 6 weeks; 2.5 mg if systolic pressure is 100–120 mmHg |
| Kidney impairment | Creatinine clearance 10–30 mL/min: halve the usual starting dose. Under 10 mL/min or on hemodialysis: start 2.5 mg. Maximum 40 mg daily |
Source: Zestril label. If blood pressure is not controlled on lisinopril alone, the label notes that a low dose of a diuretic (for example hydrochlorothiazide 12.5 mg) may be added, and that the effects of the two drugs are roughly additive.
What the research shows
Blood pressure lowering
The label summarizes two once-daily dose-response studies in 438 patients with mild to moderate hypertension. Some patients responded at 5 mg, but blood pressure fell sooner and further at 10, 20 or 80 mg. In other controlled studies, lisinopril 20–80 mg/day lowered blood pressure more than hydrochlorothiazide 12.5–50 mg/day, and about as much as atenolol or metoprolol for diastolic pressure, with somewhat greater effects on systolic pressure. It worked similarly in patients over and under 65, and less well in Black than in white patients (Zestril label).
In 115 hypertensive children aged 6–16, lisinopril lowered trough blood pressure in a dose-dependent way. In a withdrawal phase, diastolic pressure rose about 9 mmHg more in children switched to placebo than in those who stayed on the middle or high dose.
ALLHAT: lisinopril vs a thiazide-type diuretic
ALLHAT was a randomized, double-blind trial in 33,357 people aged 55 or older with hypertension and at least one other coronary risk factor, at 623 North American centers. Participants received chlorthalidone 12.5–25 mg/day (a thiazide-type diuretic, n = 15,255), amlodipine 2.5–10 mg/day (n = 9,048) or lisinopril 10–40 mg/day (n = 9,054). Mean follow-up was 4.9 years (ALLHAT, JAMA 2002).
| Outcome (6-year rate) | Lisinopril | Chlorthalidone | Relative risk (95% CI) |
|---|---|---|---|
| Primary: fatal coronary disease or nonfatal heart attack | 11.4% | 11.5% | 0.99 (0.91–1.08) |
| Combined cardiovascular disease | 33.3% | 30.9% | 1.10 (1.05–1.16) |
| Stroke | 6.3% | 5.6% | 1.15 (1.02–1.30) |
| Heart failure | 8.7% | 7.7% | 1.19 (1.07–1.31) |
| All-cause mortality | No difference | No difference | — |
Five-year systolic blood pressure was 2 mmHg higher on lisinopril than on chlorthalidone (p under 0.001). The investigators concluded that thiazide-type diuretics were superior at preventing one or more major forms of cardiovascular disease, were less expensive, and should be preferred as first-step therapy. ALLHAT did not show that lisinopril was worse at preventing heart attacks; the differences were in stroke, heart failure and combined cardiovascular events.
Heart failure: the ATLAS trial
ATLAS randomized 3,164 patients with NYHA class II–IV heart failure and an ejection fraction of 30% or less to double-blind low-dose (2.5–5 mg/day, n = 1,596) or high-dose (32.5–35 mg/day, n = 1,568) lisinopril for 39–58 months (Packer et al., Circulation 1999).
| Outcome, high dose vs low dose | Result |
|---|---|
| Death | 8% lower risk, not significant (p = 0.128) |
| Death or hospitalization for any reason | 12% lower risk (p = 0.002) |
| Hospitalizations for heart failure | 24% fewer (p = 0.002) |
| Discontinuation of study drug | Similar in both groups |
Dizziness and kidney problems were more frequent at the high dose (see the side-effect table below). The authors concluded that patients with heart failure should not generally be kept on very low doses unless those are the only doses tolerated.
After a heart attack: the GISSI-3 trial
GISSI-3 was a multicenter, randomized, unblinded trial in 19,394 patients from 200 Italian coronary care units, enrolled within 24 hours of heart attack symptoms. In a 2 × 2 factorial design, patients received 6 weeks of oral lisinopril (5 mg, then 10 mg daily) or open control, and transdermal nitroglycerin or open control. Background care included thrombolysis (72%), aspirin (84%) and beta-blockers (31%) (GISSI-3, Lancet 1994).
- 6-week mortality: lower with lisinopril, odds ratio 0.88 (95% CI 0.79–0.99). The label reports 6.4% vs 7.2% in patients who did or did not receive lisinopril, an 11% lower risk (p = 0.04).
- Death or severe ventricular dysfunction: odds ratio 0.90 (95% CI 0.84–0.98).
- Nitroglycerin alone had no independent effect.
The label adds that lisinopril-treated patients had more persistent low blood pressure (9.0% vs 3.7%) and kidney dysfunction (2.4% vs 1.1%). It also states that the open design and loss to follow-up prevent any conclusion about the 6-month combined endpoint (Zestril label).
Relevance to anabolic steroid use
High blood pressure and heart changes in anabolic-androgenic steroid (AAS) users are documented in cross-sectional studies:
- Among men doing recreational strength training, 37 current AAS users had higher 24-hour systolic blood pressure than 30 controls (132 vs 124 mmHg, p = 0.005), and systolic hypertension was more common (51% vs 17%). Current users also had higher aldosterone and lower natriuretic peptide levels, and both current and former users had stiffer aortas (Rasmussen et al., J Hypertens 2018).
- Among 140 experienced male weightlifters, 86 long-term AAS users had lower left ventricular ejection fraction than 54 nonusers (52% vs 63%), worse diastolic function and more coronary plaque (Baggish et al., Circulation 2017).
These studies describe the problem; neither tested any blood pressure drug. We found no published trials of lisinopril, or of any ACE inhibitor, in people using anabolic steroids. Whether lisinopril lowers blood pressure, reverses heart changes or prevents cardiovascular events in this group is unknown. Related library pages: losartan and telmisartan (ARBs), nebivolol and spironolactone.
Side effects and risks
Boxed warning: fetal toxicity
Drugs acting on the renin-angiotensin system reduce fetal kidney function and increase fetal and newborn illness and death when used in the second and third trimesters. The resulting low amniotic fluid (oligohydramnios) can be associated with underdeveloped lungs and skeletal deformities; newborn effects include an underdeveloped skull, absent urine output, low blood pressure, kidney failure and death. The label says to stop lisinopril as soon as possible once pregnancy is detected, and notes that oligohydramnios may not appear until after irreversible injury (Zestril label).
There are no data on lisinopril in human breast milk; it is present in rat milk. The label advises against breastfeeding during treatment.
Angioedema
Angioedema of the face, extremities, lips, tongue, glottis or larynx, including fatal cases, has occurred with ACE inhibitors including lisinopril, at any time during treatment. Involvement of the tongue, glottis or larynx can block the airway. The label says to stop the drug promptly and monitor until symptoms fully resolve. Key points from the label:
- ACE inhibitors cause angioedema more often in Black than in non-Black patients.
- People with a history of angioedema unrelated to ACE inhibitors may be at higher risk.
- Intestinal angioedema can present as abdominal pain, with or without nausea or vomiting, sometimes without any facial swelling.
- Taking an mTOR inhibitor (temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor (sacubitril) raises the risk.
In ALLHAT, 53 participants developed angioedema during active follow-up. Of these, 70% had been assigned to lisinopril, compared with 15% to chlorthalidone, 9% to doxazosin and 6% to amlodipine. 55% were Black, 23% of cases occurred within the first week, and one patient died after an episode (Piller et al., J Clin Hypertens 2006).
The label also describes life-threatening anaphylactoid (allergy-like) reactions in patients on ACE inhibitors during insect-venom desensitization, during dialysis with high-flux membranes, and during LDL apheresis with dextran sulfate.
Cough
The label lists cough as one of three adverse reactions more common on lisinopril than placebo in hypertension trials, at 2.5 percentage points above placebo. Larger analyses suggest it is more common than that:
- A review of 125 randomized trials (198,130 patients) found a pooled cough incidence of 11.48% for enalapril, a related ACE inhibitor, about nine times the rate on its label, and reported similar results for most other ACE inhibitors (Bangalore et al., Am J Med 2010).
- A network meta-analysis of 135 trials (45,420 patients) found ACE inhibitors roughly doubled cough risk vs placebo (RR 2.21, 95% CI 2.05–2.39) and tripled it vs ARBs (RR 3.2, 95% CI 2.91–3.51). The authors concluded that all ACE inhibitors carry a similar cough risk (Hu et al., J Clin Hypertens 2023).
The losartan label reports two double-blind trials in patients who had developed cough on ACE inhibitors. On rechallenge, cough returned much more often with lisinopril 20 mg than with losartan 50 mg (Cozaar label):
| Trial | Lisinopril 20 mg | Losartan 50 mg | Comparator |
|---|---|---|---|
| Study 1 (n = 135) | 69% | 17% | Hydrochlorothiazide 25 mg: 25% |
| Study 2 (n = 97) | 62% | 29% | Placebo: 35% |
Hyperkalemia, kidney function and low blood pressure
From the label (Zestril label):
- Hyperkalemia (high blood potassium): potassium above 5.7 mEq/L occurred in 2.2% of hypertension patients and 4.8% of heart failure patients in trials. Risk factors include kidney impairment, diabetes, potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes. The label advises periodic potassium checks.
- Kidney function: small, reversible rises in blood urea nitrogen and creatinine occurred in about 2% of hypertension patients on lisinopril alone, more often with diuretics or narrowed kidney arteries. People whose kidneys depend on the renin-angiotensin system (renal artery stenosis, chronic kidney disease, severe heart failure, dehydration) can develop acute kidney failure.
- Hypotension: symptomatic low blood pressure, sometimes with kidney failure or death, is more likely in heart failure with systolic pressure under 100 mmHg, ischemic heart or cerebrovascular disease, low sodium, high-dose diuretics, dialysis, or severe salt or fluid depletion. The label warns that heavy sweating, dehydration, vomiting or diarrhea can cause an excessive fall in blood pressure.
- Liver: ACE inhibitors have been linked to a rare syndrome that starts as cholestatic jaundice or hepatitis and can progress to fulminant liver necrosis and death.
Common side effects
| Setting | Adverse reactions at least 2% more common than placebo |
|---|---|
| Hypertension | Headache (+3.8%), dizziness (+3.5%), cough (+2.5%) |
| Heart failure | Low blood pressure (+3.8%), chest pain (+2.1%) |
| Acute heart attack | Low blood pressure (+5.3%), kidney dysfunction (+1.3%) |
In hypertension trials, 5.7% of patients stopped lisinopril because of adverse reactions. In ATLAS, dose-related reactions were more frequent on the high dose (Zestril label):
| ATLAS adverse reaction | High dose (n = 1,568) | Low dose (n = 1,596) |
|---|---|---|
| Dizziness | 19% | 12% |
| Hypotension | 11% | 7% |
| Creatinine increased | 10% | 7% |
| Syncope (fainting) | 7% | 5% |
| Hyperkalemia | 6% | 4% |
Less common reactions in trials (at least 1%) include fatigue, diarrhea, impotence, pancreatitis, rare blood count drops (including neutropenia), and skin reactions up to Stevens-Johnson syndrome. Small decreases in hemoglobin (≈0.4 g/dL) and hematocrit (≈1.3 percentage points) were frequent but rarely clinically important. Postmarketing reports include low sodium, mood changes and low blood sugar in people with diabetes on insulin or oral diabetes drugs.
Interactions
From the label (Zestril label):
| Drug | Effect |
|---|---|
| Diuretics | Excessive blood pressure drop when starting lisinopril; lisinopril reduces thiazide-related potassium loss |
| Potassium-sparing diuretics (spironolactone, amiloride, triamterene), potassium supplements, potassium salt substitutes | Higher risk of hyperkalemia; monitor potassium frequently |
| Insulin and oral diabetes drugs | Stronger glucose-lowering effect, risk of hypoglycemia, especially in the first month |
| NSAIDs, including COX-2 inhibitors | In older, volume-depleted or kidney-impaired patients, possible kidney deterioration including acute kidney failure (usually reversible); may blunt the blood pressure effect |
| ARBs or aliskiren (dual blockade) | More low blood pressure, hyperkalemia and kidney failure. In VA NEPHRON-D (1,448 patients with type 2 diabetes), adding lisinopril to losartan gave no extra benefit but more hyperkalemia and acute kidney injury |
| Aliskiren | Contraindicated in diabetes; avoid if GFR is under 60 mL/min |
| Sacubitril (neprilysin inhibitor) | Contraindicated; separate by at least 36 hours when switching to or from sacubitril/valsartan |
| mTOR inhibitors (temsirolimus, sirolimus, everolimus) | Higher angioedema risk |
| Lithium | Lithium toxicity reported; monitor lithium levels |
| Injectable gold (sodium aurothiomalate) | Rare nitritoid reactions: flushing, nausea, vomiting, low blood pressure |
Who should not take it
Per the label, lisinopril is contraindicated in people with:
- a history of angioedema or hypersensitivity from a previous ACE inhibitor;
- hereditary or idiopathic angioedema;
- current use of a neprilysin inhibitor such as sacubitril, or within 36 hours of switching;
- diabetes, if also taking aliskiren.
It should be stopped as soon as possible if pregnancy is detected (boxed warning). Safety has not been established in children under 6 or in children with GFR under 30 mL/min/1.73 m².
Monitoring
The label recommends periodic checks of kidney function and serum potassium, and close blood pressure monitoring at the start of treatment in people at risk of hypotension, particularly during the first two weeks and after any dose increase of lisinopril or a diuretic. Patients are told to report swelling of the face, lips, tongue or throat, trouble swallowing or breathing, light-headedness or fainting, and signs of infection such as fever or sore throat (Zestril label).
Legal status and use in sport
In the US, lisinopril is a prescription-only drug (Zestril label).
Lisinopril and ACE inhibitors as a class are not named on the WADA 2026 Prohibited List. Hydrochlorothiazide, the diuretic in combination tablets such as Zestoretic, is prohibited at all times under class S5 (diuretics and masking agents).
Key takeaways
- A long-established ACE inhibitor. Lisinopril blocks the enzyme that makes angiotensin II. It is not metabolized, is cleared unchanged by the kidneys, and has an effective half-life of about 12 hours.
- Outcome data in three settings. It lowered 6-week mortality after heart attack in GISSI-3, higher doses reduced hospitalizations in heart failure in ATLAS, and in ALLHAT it matched chlorthalidone for heart attacks but had more strokes, heart failure and combined cardiovascular events.
- Cough is common. Trial data suggest cough is far more common than the label’s figure; ARBs such as losartan cause much less of it.
- Angioedema is rare but can be fatal. It can occur at any time during treatment, is more common in Black patients, and prior angioedema is a contraindication.
- Watch potassium and kidneys. Hyperkalemia and kidney injury are more likely with kidney disease, diabetes, potassium-sparing diuretics, NSAIDs or other renin-angiotensin blockers. Fetal toxicity carries a boxed warning.
- Untested in steroid users. AAS use is linked to higher blood pressure and heart changes, but no trials have tested lisinopril in this group.
Sources
- Upsher-Smith Laboratories. Zestril (lisinopril) tablets prescribing information (revised November 2024). DailyMed.
- US Food and Drug Administration. Drugs@FDA: Zestril (NDA 019777), Prinivil (NDA 019558), Zestoretic (NDA 019888) and Qbrelis (NDA 208401), approval history. FDA.
- ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981–2997. PubMed.
- Piller LB, Ford CE, Davis BR, et al. Incidence and predictors of angioedema in elderly hypertensive patients at high risk for cardiovascular disease: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2006;8(9):649–656. PubMed.
- Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation. 1999;100(23):2312–2318. PubMed.
- Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994;343(8906):1115–1122. PubMed.
- Li EC, Heran BS, Wright JM. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev. 2014;(8):CD009096. PubMed.
- Bangalore S, Kumar S, Messerli FH. Angiotensin-converting enzyme inhibitor associated cough: deceptive information from the Physicians’ Desk Reference. Am J Med. 2010;123(11):1016–1030. PubMed.
- Hu Y, Liang L, Liu S, et al. Angiotensin-converting enzyme inhibitor induced cough compared with placebo, and other antihypertensives: a systematic review, and network meta-analysis. J Clin Hypertens (Greenwich). 2023;25(8):661–688. PubMed.
- Organon LLC. Cozaar (losartan potassium) tablets prescribing information. DailyMed.
- Rasmussen JJ, Schou M, Madsen PL, et al. Increased blood pressure and aortic stiffness among abusers of anabolic androgenic steroids: potential effect of suppressed natriuretic peptides in plasma? J Hypertens. 2018;36(2):277–285. PubMed.
- Baggish AL, Weiner RB, Kanayama G, et al. Cardiovascular toxicity of illicit anabolic-androgenic steroid use. Circulation. 2017;135(21):1991–2002. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List (in effect January 1, 2026). WADA 2026 Prohibited List.