ACE inhibitor
ATC code: C09AA01 (Captopril)
Brand names
Capoten, Captoril, Acepril
Inhibits angiotensin-converting enzyme, reduces angiotensin II formation and bradykinin breakdown. Used for hypertension and heart failure; short half-life requires 2–3 daily doses.
First line
ACE inhibitors slow the progression of diabetic nephropathy in patients with type 1 diabetes and albuminuria, as shown in the Lewis trial (1993) of captopril 75 mg daily: 48 percent reduction in creatinine doubling. KDIGO 2022 recommends ACE inhibitors or ARBs at the maximally tolerated dose in patients with diabetes and A2–A3 albuminuria. In current practice captopril has been displaced by lisinopril and ramipril, which are dosed once daily.
Second line
Captopril lowers blood pressure in adults, with efficacy established by large ACE-inhibitor trials. 2024 and NG136 keep ACE inhibitors as first-line therapy for hypertension in patients under 55 years and not of Black ancestry. Among ACE inhibitors, captopril has been displaced by enalapril, lisinopril, and perindopril because of the need for 2–3 daily doses and the relatively high rate of skin rash. Today captopril is used mainly for sublingual treatment of hypertensive emergencies at 25 mg.
Not used during pregnancy. Contraindicated in bilateral renal artery stenosis. Patients over 75 are started at the lowest dose because of orthostatic hypotension risk.
Sources
Adjunct
Captopril reduces mortality and hospitalization in chronic heart failure with reduced ejection fraction, as shown in the SAVE trial (1992) in post-MI patients with EF 40 percent or below. 2023 and NG106 include ACE inhibitors as a baseline component of quadruple therapy (with a beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor). Captopril is rarely used in this role because of 2–3 daily dosing; enalapril, lisinopril, and ramipril are preferred.
In patients with eGFR below 30 mL/min/1.73 m² the dose is reduced; with potassium above 5.5 mmol/L the drug is held until corrected.
Sources
Boxed warning
FDA boxed warning: when pregnancy is detected, ACE inhibitors are discontinued immediately. Use in the second and third trimesters is associated with oligohydramnios, pulmonary hypoplasia, limb contractures, neonatal hypotension, and renal failure.
FDA category D in the second and third trimesters. The first trimester was historically labeled category C, but current data show an increased risk of cardiovascular and central nervous system malformations. When pregnancy is planned, captopril is replaced with a safer antihypertensive (methyldopa, labetalol, extended-release nifedipine).
Captopril passes into breast milk in minimal amounts. LactMed lists it as compatible with breastfeeding when maternal therapy is required. In preterm infants and newborns under one month, alternatives are preferred.
captopril is evaluated for the following indications with varying evidence strength: Diabetic nephropathy (evidence tier A), Hypertension (evidence tier A), Heart failure with reduced ejection fraction (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of captopril (≥ 1 in 100): Dry cough (5–20 percent of patients, common cause of discontinuation), Hypotension, especially after the first dose, Hyperkalemia, Taste disturbance (metallic taste, dysgeusia), Skin rash (more frequent than with other ACE inhibitors, linked to the sulfhydryl group). See the Safety section for uncommon and serious reactions.
FDA category D. FDA category D in the second and third trimesters. The first trimester was historically labeled category C, but current data show an increased risk of cardiovascular and central nervous system malformations. When pregnancy is planned, captopril is replaced with a safer antihypertensive (methyldopa, labetalol, extended-release nifedipine).
Captopril passes into breast milk in minimal amounts. LactMed lists it as compatible with breastfeeding when maternal therapy is required. In preterm infants and newborns under one month, alternatives are preferred.
captopril is contraindicated in: History of angioedema with ACE inhibitors; Pregnancy (second and third trimester); Bilateral renal artery stenosis or stenosis of a solitary kidney artery; Hyperkalemia above 5.5 mmol/L; Concomitant aliskiren in patients with diabetes or eGFR below 60 mL/min/1.73 m². Full list in the Safety section.
FDA boxed warning: when pregnancy is detected, ACE inhibitors are discontinued immediately. Use in the second and third trimesters is associated with oligohydramnios, pulmonary hypoplasia, limb contractures, neonatal hypotension, and renal failure.
dysgeusia reflects a temporary change in taste receptor sensitivity, resolves spontaneously or after withdrawal, and is not associated with malignancy.
the combination is standard in hypertension and HFrEF. It requires monitoring of potassium and creatinine.
ACE inhibitors do not cause dependence. Long-term use reflects the chronic nature of hypertension and heart failure, not a drug effect.