# Lisinopril
**Lisinopril** is an orally active, long-acting angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure, heart failure, and to improve survival after a heart attack. It is sold under brand names including Prinivil, Zestril, and Qbrelis, and in combination with hydrochlorothiazide as Zestoretic.[1](https://medlineplus.gov/druginfo/meds/a692051.html) Unlike captopril, it contains no sulfhydryl group, and unlike [enalapril](https://www.edgepedia.org/enalapril) and related compounds it is not an ester prodrug: it is absorbed in its active form and requires no liver biotransformation.[2](https://pubmed.ncbi.nlm.nih.gov/2550635/)
| Key fact | Detail |
|---|---|
| Drug class | Orally active, nonsulfhydryl ACE inhibitor; not metabolized and not bound to protein[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) |
| Approved uses | High blood pressure in adults and children 6 years and older; heart failure (with other medications); improved survival after heart attack[1](https://medlineplus.gov/druginfo/meds/a692051.html) |
| Pharmacokinetics | Bioavailability about 25%; peak serum concentrations 6-8 h after dosing; eliminated unchanged in urine; half-life controlling accumulation 12-13 h[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) |
| Blood pressure effect | Onset within 2 h, peak around 6 h, lasting at least 24 h; once-daily monotherapy lowers systolic pressure 11-15% and diastolic 13-17%[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) |
| Metabolic profile | Does not produce hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia; has natriuretic properties[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) |
| Renal dosing | Significant accumulation occurs with severe renal impairment (creatinine clearance ≤30 ml/min); dose reduction is required in renal failure[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) • [4](https://pubmed.ncbi.nlm.nih.gov/7995322/) |
| Pregnancy | Contraindicated; lisinopril may harm the fetus[1](https://medlineplus.gov/druginfo/meds/a692051.html) |
## Mechanism and pharmacology
Lisinopril inhibits angiotensin-converting enzyme, which reduces plasma angiotensin II and aldosterone and increases plasma renin activity. The lowering of blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, but lisinopril remains antihypertensive even in patients with low-renin hypertension.[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) • [5](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a2f31909-3cda-4580-adfa-e9992d8c0885) In practical terms, the drug makes blood vessels relax and widen, so blood flows more smoothly and the heart can pump blood more efficiently.[6](https://www.nhs.uk/medicines/lisinopril/)
The pharmacokinetic profile supports once-daily dosing. Absorption after oral administration is slow, but the absorbed drug is immediately active without hepatic biotransformation, and steady state is reached in 2-3 days with little accumulation in normal kidney function.[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) • [2](https://pubmed.ncbi.nlm.nih.gov/2550635/) [Bioavailability](https://www.edgepedia.org/bioavailability) is about 25% and is not significantly affected by food, age, or coadministration of hydrochlorothiazide, propranolol, digoxin, or glibenclamide.[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) Because the drug is eliminated by glomerular filtration, patients with severe renal impairment accumulate it, and dose adjustment is needed.[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) • [4](https://pubmed.ncbi.nlm.nih.gov/7995322/) In elderly patients, maximum blood levels and area under the plasma concentration curve are doubled.[7](https://admin.greenbook.nafdac.gov.ng/uploadImage/smpc_files/2024/09/14/202409145ba22477-9f6b-5460-a002-568e1fe4add3.pdf)
## Approved uses
Lisinopril is used alone or in combination with other medications to treat high blood pressure in adults and in children 6 years of age and older. It is used in combination with other medications to treat heart failure, and it is also used to improve survival after a heart attack.[1](https://medlineplus.gov/druginfo/meds/a692051.html) The NHS additionally lists kidney problems caused by diabetes among its uses.[6](https://www.nhs.uk/medicines/lisinopril/)
In heart failure refractory to conventional treatment with digitalis and diuretics, lisinopril increases cardiac output and decreases pulmonary capillary wedge pressure and mean arterial pressure.[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) The ATLAS trial, published in *Circulation* in 1999, examined whether higher-dose lisinopril provides additional benefit over lower-dose lisinopril in chronic heart failure.[8](https://healthrx.com/lisinopril/history-development) A Cochrane review of heart failure treatments found that low-dose and high-dose lisinopril seem equally effective at reducing mortality, based on moderate-quality evidence.[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC2907608/)
## Effectiveness compared with other drugs
Within its class, head-to-head trials show lisinopril producing greater systolic and diastolic blood pressure reductions than hydrochlorothiazide, similar diastolic reductions to atenolol and metoprolol but superior systolic reduction, and comparable reductions to nifedipine.[3](https://pubmed.ncbi.nlm.nih.gov/2442549/) Adding hydrochlorothiazide enhances its antihypertensive effect.[3](https://pubmed.ncbi.nlm.nih.gov/2442549/)
A Cochrane review of 92 trials in 12,954 participants found no clinically meaningful blood pressure lowering differences between different ACE inhibitors; as a class, at half the manufacturers' maximum recommended dose and above, they lower blood pressure by about 8 mm Hg systolic and 5 mm Hg diastolic at trough, and 60 to 70% of that effect is achieved with the recommended starting doses.[10](https://www.cochrane.org/evidence/CD003823_ace-inhibitors-treatment-high-blood-pressure) A network meta-analysis found ACE inhibitors and angiotensin receptor blockers similarly effective in lowering blood pressure, all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke in essential hypertension, with ACE inhibitors more helpful in preventing heart failure or its hospitalization (risk ratio 0.71, 95% CI 0.54 to 0.93).[11](https://pubmed.ncbi.nlm.nih.gov/30518809/)
## History and development
Lisinopril belongs to the first generation of ACE inhibitors designed in the late 1970s and early 1980s, alongside captopril and enalaprilat, a group described as one of the early examples of rational drug design.[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC7097707/) [Captopril](https://www.edgepedia.org/captopril) became the first [ACE inhibitor](https://www.edgepedia.org/ace-inhibitor) in clinical use, first approved in 1981.[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC7097707/) Lisinopril, the lysine derivative of enalaprilat, was patented in 1978 and developed by Merck, which obtained FDA approval for the treatment of hypertension in 1987 and congestive heart failure in 1993.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC11803303/) The Zestril label records initial U.S. approval of lisinopril tablets in 1988.[5](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a2f31909-3cda-4580-adfa-e9992d8c0885)
## Side effects and precautions
Common side effects include headache, nausea, diarrhea, dizziness especially on standing up quickly, a dry cough that does not go away, and kidney problems detected through blood tests.[6](https://www.nhs.uk/medicines/lisinopril/) MedlinePlus lists cough, dizziness, headache, excessive tiredness, nausea, diarrhea, weakness, rash, and decreased sexual ability among effects patients should report if severe or persistent.[1](https://medlineplus.gov/druginfo/meds/a692051.html) Serious but uncommon or rare effects include allergic reaction (anaphylaxis), kidney failure, and angioedema, swelling of areas such as the lips, tongue, and face; the chance of angioedema is higher in black patients.[6](https://www.nhs.uk/medicines/lisinopril/)
Pregnancy is the central contraindication: lisinopril should not be taken during pregnancy because it can affect development of the baby's kidneys, skull, lungs, and joints, reduce amniotic fluid, and increase the risk of stillbirth.[1](https://medlineplus.gov/druginfo/meds/a692051.html) • [6](https://www.nhs.uk/medicines/lisinopril/) It also may not be suitable for people who have had angioedema, or kidney or liver problems.[6](https://www.nhs.uk/medicines/lisinopril/)
Several interactions require caution or avoidance. Nonprescription aspirin and NSAIDs such as ibuprofen and naproxen, and potassium supplements, can interact with lisinopril.[1](https://medlineplus.gov/druginfo/meds/a692051.html) Patients taking valsartan and sacubitril (Entresto), or who stopped it within the previous 36 hours, should generally not take lisinopril, and the same applies to patients with diabetes taking aliskiren.[1](https://medlineplus.gov/druginfo/meds/a692051.html) The NHS also lists lithium, diuretics, anticoagulants such as heparin, and several antibiotics and antidepressants among medicines that may not mix well with the drug.[6](https://www.nhs.uk/medicines/lisinopril/) Diarrhea, vomiting, dehydration, or heavy sweating can cause a drop in blood pressure leading to lightheadedness and fainting.[1](https://medlineplus.gov/druginfo/meds/a692051.html)
## Dosing and administration
Lisinopril comes as a tablet or a solution (liquid) taken by mouth, usually once a day at the same time each day. Doctors typically start with a low dose and increase it gradually over days or weeks to reduce the chance of side effects, and regular blood tests or other checks may be performed during treatment.[1](https://medlineplus.gov/druginfo/meds/a692051.html) • [6](https://www.nhs.uk/medicines/lisinopril/) The liquid solution should be measured with an oral syringe, not a household spoon.[1](https://medlineplus.gov/druginfo/meds/a692051.html) In a clinical study of 115 hypertensive pediatric patients aged 6 to 16, patients weighing under 50 kg received 0.625, 2.5, or 20 mg daily and those weighing 50 kg or more received 1.25, 5, or 40 mg daily.[14](https://pdf.hres.ca/dpd_pm/00037485.PDF) Lisinopril controls blood pressure but does not cure the underlying condition, so treatment continues even when the patient feels well.[1](https://medlineplus.gov/druginfo/meds/a692051.html)
## References
1. [Lisinopril: MedlinePlus Drug Information, ASHP patient medication information](https://medlineplus.gov/druginfo/meds/a692051.html)
2. [Case DE (1989). The clinical pharmacology of lisinopril. Journal of Human Hypertension](https://pubmed.ncbi.nlm.nih.gov/2550635/)
3. [Gomez HJ, Cirillo VJ, Moncloa F (1987). The clinical pharmacology of lisinopril. Journal of Cardiovascular Pharmacology](https://pubmed.ncbi.nlm.nih.gov/2442549/)
4. [Neubeck M et al. (1994). Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure. European Journal of Clinical Pharmacology](https://pubmed.ncbi.nlm.nih.gov/7995322/)
5. [Zestril (lisinopril) tablets, Full Prescribing Information, DailyMed](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a2f31909-3cda-4580-adfa-e9992d8c0885)
6. [Lisinopril: a medicine to treat high blood pressure, NHS](https://www.nhs.uk/medicines/lisinopril/)
7. [Leypril 5 / Leypril 10 Summary of Product Characteristics, NAFDAC Greenbook](https://admin.greenbook.nafdac.gov.ng/uploadImage/smpc_files/2024/09/14/202409145ba22477-9f6b-5460-a002-568e1fe4add3.pdf)
8. [Lisinopril History and Development, HealthRX](https://healthrx.com/lisinopril/history-development)
9. [Heart failure, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2907608/)
10. [Heran BS et al. (2008). Blood pressure lowering efficacy of ACE inhibitors for primary hypertension, Cochrane Database of Systematic Reviews](https://www.cochrane.org/evidence/CD003823_ace-inhibitors-treatment-high-blood-pressure)
11. [A systematic review and network meta-analysis of the comparative efficacy of ACE inhibitors and ARBs in hypertension, Journal of Human Hypertension](https://pubmed.ncbi.nlm.nih.gov/30518809/)
12. [Acharya A et al. (2003). Ace revisited: A new target for structure-based drug design, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7097707/)
13. [A perspective on small molecules targeting the renin-angiotensin-aldosterone system, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11803303/)
14. [ACTION AND CLINICAL PHARMACOLOGY, Health Canada product monograph](https://pdf.hres.ca/dpd_pm/00037485.PDF)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Cardiovascular, metabolic, and endocrine drugs › Cardiovascular drugs*
*Initially written Sep 17, 2026 · Reviewed: Sep 17, 2026; Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license