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.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Captopril is a short-acting angiotensin-converting enzyme (ACE) inhibitor. It is prescribed for hypertension and heart failure ( 2023, SEH-LELHA, 2017). In anti-aging regimens, captopril is used in healthy normotensives as a quick vasodilator to protect vessels from aging. In people with normal blood pressure, captopril does not work: no clinical studies of such use exist, and a vessel-rejuvenating effect has not been demonstrated. The drug causes a dry cough (10-20% of patients), elevated blood potassium, angioedema in predisposed people (life-threatening), and acute kidney injury in renal artery stenosis. If captopril was prescribed to a person with normal blood pressure, consider seeking a second opinion.
10 pairs found. Sorted from critical to minor.
Mechanism
The combination raises risk of hypersensitivity reactions and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema). The mechanism is not fully established; presumed to be an immune reaction to metabolites of both drugs in chronic kidney disease.
Symptoms
Rash, fever, eosinophilia, lymphadenopathy (DRESS syndrome). Severe cases: bullous rash with skin sloughing (Stevens-Johnson syndrome), angioedema of face and tongue. Symptoms appear 1–8 weeks into the combination.
Management
Avoid the combination, especially in chronic kidney disease (higher risk). Alternative to ACE-I: an ARB (losartan) for antihypertensive needs. If rash or fever emerges, stop both drugs immediately.
Mechanism
Trimethoprim (a co-trimoxazole component) blocks sodium channels in the collecting duct epithelium (amiloride-like mechanism) and reduces potassium secretion. Captopril (ACE-I) additionally retains potassium via aldosterone suppression.
Symptoms
Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.
Management
During co-trimoxazole therapy (usually 5–10 days), check potassium 3–5 days after start. In older patients and chronic kidney disease, prefer alternative antibiotics: nitrofurantoin or fosfomycin for urinary tract infection.
Mechanism
Dual RAAS blockade (ACE-I + ARB). Additive hyperkalaemia, hypotension, and acute kidney injury risk without added benefit.
Symptoms
Weakness, postural dizziness, syncope. Reduced urine output, rising creatinine. Weakness and paraesthesia from hyperkalaemia.
Management
The combination is not prescribed. Choose one: ACE-I if tolerated, ARB if there is a dry cough.
Sources
Mechanism
Captopril (ACE-I) reduces aldosterone synthesis, while spironolactone directly blocks aldosterone receptors. Both retain potassium. In chronic kidney disease and older patients, severe hyperkalaemia risk reaches 10–15% in the first weeks.
Symptoms
Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.
Management
The combination is appropriate in heart failure. Check potassium and creatinine 1 week after start, then monthly. If potassium exceeds 5.5 mmol/L, reduce the spironolactone dose; above 6.0 mmol/L, stop one of the drugs.
Sources
Mechanism
Dual RAAS blockade (ACE-I + ARB). The ONTARGET trial showed increased hyperkalaemia, hypotension, and acute kidney injury without outcome improvement. Contraindicated in most clinical situations.
Symptoms
Muscle weakness, paraesthesia, slowed pulse, arrhythmias. ECG: peaked T waves, widened QRS. Severe cases progress to cardiac arrest.
Management
The combination is not prescribed. Choose one: ACE-I (captopril) if tolerated, ARB (telmisartan) if there is a dry cough.
Mechanism
Dual RAAS blockade (ACE-I + ARB). Additive hyperkalaemia, hypotension, and acute kidney injury risk without added benefit.
Symptoms
Weakness, postural dizziness, syncope. Reduced urine output, rising creatinine. Weakness and paraesthesia from hyperkalaemia.
Management
The combination is not prescribed. Choose one: ACE-I if tolerated, ARB if there is a dry cough or intolerance.
Sources
Mechanism
At analgesic doses (above 1 g/day), aspirin suppresses vasodilator prostaglandins and weakens the ACE-I's hypotensive effect. At cardioprotective doses (75–100 mg), the effect is minimal.
Symptoms
Gradual blood pressure rise at high aspirin doses. At cardioprotective doses, no significant changes.
Management
Cardioprotective aspirin doses (75–100 mg) are acceptable without adjustment. At high doses, monitor blood pressure and increase captopril if needed. Alternative analgesic: paracetamol.
Mechanism
Additive hypotension. Alprazolam sedation may mask early orthostatic symptoms.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.
Management
In older patients, check standing and sitting blood pressure 1–2 weeks after start. Alternative anxiolytic: hydroxyzine or a short lorazepam course.
Mechanism
Additive orthostatic hypotension via different mechanisms. Captopril (ACE-I) dilates vessels; amitriptyline blocks α1-adrenoceptors and reduces compensatory response.
Symptoms
Postural dizziness, syncope, fatigue. Older patients: fall and fracture risk.
Management
In older patients, check standing and sitting blood pressure 1–2 weeks after starting amitriptyline. For neuropathic pain, alternative: gabapentin or pregabalin.
Mechanism
Systemic budesonide retains sodium and water via mineralocorticoid effect (weaker than prednisolone), antagonising the ACE inhibitor's antihypertensive effect. Inhaled budesonide does not clinically affect BP.
Symptoms
On long-term therapy: return or rise of blood pressure, leg oedema. Hyperkalaemia possible with reduced renal function.
Management
For short systemic budesonide courses (3–7 days), no specific adjustment needed. For long-term therapy, check BP weekly in the first month. If BP rises, intensify antihypertensives or switch to an oral corticosteroid with less mineralocorticoid activity (methylprednisolone). Inhaled budesonide with captopril is unproblematic.
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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).
Fully compatible. Hale L2. RID 0.02% – lowest among ACE inhibitors. Drug of choice for HTN in nursing per ACOG 2020 alongside enalapril. Contraindicated in pregnancy.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Captopril is evaluated for the following indications with varying evidence strength: Hypertension (evidence tier A), Diabetic nephropathy (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).
Fully compatible. Hale L2. RID 0.02% – lowest among ACE inhibitors. Drug of choice for HTN in nursing per ACOG 2020 alongside enalapril. Contraindicated in pregnancy.
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.