Formulary
Enalapril: Uses, Dosing, Side Effects and Indian Brand Names
Enalapril is an ACE inhibitor with landmark evidence for mortality reduction in heart failure, used as first-line therapy for hypertension, diabetic nephropathy, and left ventricular dysfunction.
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Clinically reviewed by Awaiting clinical review
Enalapril: Uses, Dosing, Side Effects and Indian Brand Names
Enalapril is an ACE inhibitor with landmark evidence for mortality reduction in heart failure, used as first-line therapy for hypertension, diabetic nephropathy, and left ventricular dysfunction.
NEET PG High-Yield: CONSENSUS and SOLVD trials (mortality benefit in heart failure). Prodrug (enalapril) vs active drug (enalaprilat -- only IV ACE inhibitor). Dry cough mechanism (bradykinin). Contraindicated in bilateral renal artery stenosis (efferent arteriolar dilation collapses GFR). Teratogenic in pregnancy. The 'triple whammy' of ACEI + diuretic + NSAID causing AKI. First-dose hypotension: withhold diuretics 2-3 days before starting.
Clinical overview
Enalapril is a long-acting ACE inhibitor and one of the most extensively studied cardiovascular drugs in history. The landmark CONSENSUS and SOLVD trials established ACE inhibitors as the cornerstone of heart failure management, demonstrating significant mortality reduction in patients with left ventricular systolic dysfunction. Enalapril is a prodrug -- the oral formulation is inactive and must undergo hepatic esterase-mediated conversion to the active metabolite enalaprilat. This is clinically relevant because enalaprilat is the only ACE inhibitor available for intravenous use, useful in hypertensive emergencies when oral administration is not possible. ACE inhibitors are renoprotective in diabetic nephropathy, reducing proteinuria and slowing progression to end-stage renal disease, making them first-line in hypertensive diabetics with albuminuria. The dry cough, caused by accumulation of bradykinin and substance P in the airways, occurs in up to 15-20% of patients and is more common in women and individuals of South Asian and East Asian descent -- a point of particular relevance in Indian practice. If cough is intolerable, switching to an ARB (losartan, telmisartan) is appropriate as ARBs do not inhibit bradykinin degradation. Angioedema is rare but potentially fatal, especially when involving the tongue or larynx.
Pharmacological class
Enalapril belongs to the Angiotensin-Converting Enzyme (ACE) Inhibitors class. Prodrug that is hydrolysed in the liver to enalaprilat, which competitively inhibits angiotensin-converting enzyme (ACE/kininase II). This prevents conversion of angiotensin I to angiotensin II (reducing vasoconstriction and aldosterone secretion) and inhibits bradykinin degradation (contributing to vasodilation but also causing the characteristic dry cough).
Indian brand names and formulations
Available as: Envas (Cadila), Enapril (Cipla), Enacard (Merck/Organon), Renitec (MSD/Glenmark).
Tablets: 2.5 mg, 5 mg, 10 mg, 20 mg. Enalaprilat injection: 1.25 mg/mL for IV use (limited availability in India). Fixed-dose combinations available with hydrochlorothiazide.
Regulatory status
Enalapril is classified under Schedule H in India under the Drugs and Cosmetics Act, 1940. Prescription-only. Listed on NLEM. Available at Jan Aushadhi centres.
Indications
- Hypertension (first-line, especially with diabetes or CKD)
- Heart failure with reduced ejection fraction (HFrEF)
- Left ventricular dysfunction post-myocardial infarction
- Diabetic nephropathy (to reduce proteinuria and slow CKD progression)
- Asymptomatic left ventricular systolic dysfunction (prevention of heart failure)
Dosing
Hypertension: Start 5 mg once daily, usual maintenance 10-20 mg daily in 1-2 divided doses, maximum 40 mg/day. Heart failure: Start 2.5 mg twice daily, titrate to target dose of 10-20 mg twice daily as tolerated. Renal impairment (CrCl <30 mL/min): start at 2.5 mg daily.
Contraindications
- Bilateral renal artery stenosis (or stenosis of artery to a single functioning kidney)
- History of angioedema with any ACE inhibitor
- Pregnancy (teratogenic -- causes renal agenesis and oligohydramnios in second and third trimesters)
- Concomitant use with aliskiren in diabetic patients
- Hyperkalaemia (K+ >5.5 mEq/L)
Adverse effects
- Dry cough (15-20%, more common in South Asians and women; due to bradykinin accumulation)
- Hyperkalaemia (especially with potassium-sparing diuretics or in CKD)
- First-dose hypotension (especially in volume-depleted patients or those on high-dose diuretics)
- Angioedema (rare but life-threatening; more common in African descent populations)
- Acute kidney injury (usually reversible, occurs in bilateral renal artery stenosis)
- Dysgeusia (altered taste, more common with captopril)
Drug interactions
- Potassium-sparing diuretics (spironolactone, amiloride) and potassium supplements: additive hyperkalaemia risk; monitor K+ closely
- NSAIDs: reduce antihypertensive effect and increase risk of AKI (the triple whammy: ACEI + diuretic + NSAID)
- Lithium: ACE inhibitors reduce lithium clearance, risk of toxicity; monitor lithium levels
- Aliskiren: combination contraindicated in diabetes (ALTITUDE trial -- increased adverse events)
Pregnancy and lactation
Contraindicated (Category D in 2nd/3rd trimester, Category C in 1st trimester but should be avoided throughout). ACE inhibitors cause renal tubular dysgenesis, oligohydramnios, pulmonary hypoplasia, and foetal death. Women of childbearing age must use contraception. Switch to labetalol, nifedipine, or methyldopa if pregnancy is planned.
Exam-style clinical scenario
A 50-year-old diabetic man with microalbuminuria (albumin-creatinine ratio 150 mg/g) and BP 150/95 mmHg. Which antihypertensive provides both BP control and renoprotection? Enalapril (or any ACE inhibitor) -- it reduces intraglomerular pressure by dilating the efferent arteriole, reducing proteinuria independent of its blood pressure lowering effect.
Cost in India
Rs 20-60 for a strip of 10 tablets (5 mg). Listed on NLEM and available through Jan Aushadhi.
Clinical governance
Author: MedNext Editorial Team. Clinical reviewer: Awaiting clinical review. Jurisdiction: India (Drugs and Cosmetics Act, 1940). Sources: CIMS India, Indian Pharmacopoeia. Publication state: Awaiting clinical review. Correction: Report errors at support@mednext.academy.
Frequently Asked Questions
Why do ACE inhibitors cause cough but ARBs do not?
ACE is identical to kininase II, the enzyme that degrades bradykinin. ACE inhibitors block both angiotensin I conversion AND bradykinin degradation. Accumulated bradykinin stimulates C-fibre nerve endings in the airways, triggering cough. ARBs block the AT1 receptor downstream and do not affect kininase II, so bradykinin metabolism is unaffected.
How should enalapril be monitored?
Check serum creatinine and potassium at baseline, 1-2 weeks after starting, and after each dose increase. A rise in creatinine of up to 30% from baseline is acceptable and expected (reflects reduced efferent arteriolar tone). A rise >30% should prompt investigation for renal artery stenosis.
Why is enalapril contraindicated in bilateral renal artery stenosis?
In renal artery stenosis, the kidney maintains GFR by angiotensin II-mediated constriction of the efferent arteriole. ACE inhibitors remove this compensatory mechanism, causing efferent arteriolar dilation, a precipitous drop in GFR, and acute kidney injury. This is bilateral or functionally bilateral (single kidney with stenosis).
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