Schedule H

Oral

• Tablets: 2.5 mg, 5 mg, 10 mg

• Oral solution: 1 mg/mL (limited availability; may require extemporaneous preparation for paediatric use)

Note: Enalapril is a prodrug; it is converted to the active metabolite enalaprilat by hepatic esterases.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Essential Hypertension

Parameter Dose Clinical Notes

Starting dose 5 mg orally once daily If on diuretics or volume-depleted: start at 2.5 mg once daily

Titration Increase by 5 mg increments every 1–2 weeks Based on BP response

Usual maintenance dose 10–20 mg once daily May give in 1–2 divided doses

Maximum dose 40 mg/day (usually 20 mg twice daily)

Note: First-dose hypotension is more likely in patients on diuretics, volume-depleted, or with heart failure. Consider withholding diuretic for 2–3 days before initiating or starting with 2.5 mg.

1. Heart Failure with Reduced Ejection Fraction (HFrEF)

Parameter Dose Clinical Notes

Starting dose 2.5 mg orally twice daily Start lower if hypotensive or on high-dose diuretics

Titration Double dose every 1–2 weeks as tolerated Monitor BP, renal function, potassium

Usual maintenance dose 10–20 mg twice daily Target evidence-based dose

Maximum dose 20 mg twice daily (40 mg/day)

Used in combination with beta-blockers, diuretics, and mineralocorticoid receptor antagonists as per guideline-directed medical therapy (GDMT).

1. Asymptomatic Left Ventricular Dysfunction (LVEF ≤35%)

Parameter Dose Clinical Notes

Starting dose 2.5 mg orally twice daily

Titration Increase gradually over 2–4 weeks Target dose: 10 mg twice daily

Usual maintenance dose 10 mg twice daily

Maximum dose 20 mg twice daily

Reduces progression to symptomatic heart failure and improves survival.

1. Post-Myocardial Infarction (with LV Dysfunction)

Parameter Dose Clinical Notes

Starting dose 2.5 mg orally twice daily Initiate within 24 hours if haemodynamically stable

Titration Increase as tolerated over 2–4 weeks

Usual maintenance dose 10 mg twice daily

Maximum dose 20 mg twice daily

Secondary Indications — Adults (Off-label, if any)

1. Diabetic Nephropathy with Proteinuria — OFF-LABEL

Parameter Details

Indication Type 1 or Type 2 diabetes with albuminuria/proteinuria for renal protection

Dose 5–20 mg once daily

Duration Long-term; continued as long as tolerated

Specialist only Yes — Nephrology for CKD Stage 3 or worse

Evidence basis RENAAL, IDNT trials (class effect for ACE inhibitors/ARBs); Indian nephrology practice

1. Non-Diabetic Chronic Kidney Disease with Proteinuria — OFF-LABEL

Parameter Details

Indication Proteinuric CKD for slowing disease progression

Dose 5–20 mg once daily; start 2.5 mg if eGFR <30

Duration Long-term

Specialist only Yes — Nephrology

Evidence basis REIN trial; Indian nephrology practice; CSI/ISNWG guidelines

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

1. Hypertension (Children ≥1 month of age)

Age/Weight Starting Dose Titration Maximum Dose

Infants (1–12 months) 0.04–0.08 mg/kg/day once daily Increase every 1–2 weeks based on response 0.5 mg/kg/day

Children (1–16 years, <50 kg) 0.08 mg/kg/day once daily (max starting: 5 mg) Double at 1–2 week intervals 0.6 mg/kg/day (max 40 mg/day)

Adolescents (≥50 kg) 2.5–5 mg once daily As per adult titration 40 mg/day

Dosing Summary:

• Starting dose: 0.08 mg/kg/day orally once daily (maximum initial dose: 5 mg)

• Titration: Double dose every 1–2 weeks based on BP response

• Usual maintenance dose: 0.08–0.6 mg/kg/day once daily

• Maximum dose: 0.6 mg/kg/day; not to exceed 40 mg/day

Monitoring:

• Blood pressure at each visit

• Serum creatinine and potassium within 1–2 weeks of initiation and after dose changes

• Growth parameters

Secondary Indications — Paediatrics (Off-label, if any)

Heart Failure (Congenital Heart Disease, Cardiomyopathy) — OFF-LABEL

Parameter Details

Indication HFrEF secondary to congenital heart disease or dilated cardiomyopathy

Starting dose 0.04–0.08 mg/kg/day orally in 1–2 divided doses

Titration Increase gradually over 2–4 weeks

Maximum dose 0.5 mg/kg/day in 1–2 divided doses

Specialist only Yes — Paediatric cardiology

Evidence basis IAP guidelines; paediatric cardiology protocols from Indian tertiary centres

Not recommended below 1 month of age except under specialist paediatric cardiology/nephrology supervision due to increased risk of hypotension and renal effects.

30 Standard starting dose Standard maximum Monitor renal function and potassium

10–30 2.5 mg once daily 10–20 mg/day Titrate cautiously; close monitoring essential

<10 (non-dialysis) 2.5 mg once daily 10 mg/day Avoid if possible; use with extreme caution

Haemodialysis 2.5 mg on dialysis days 10 mg/day Administer after dialysis; enalaprilat is dialyzable

Peritoneal dialysis 2.5 mg once daily 10 mg/day Monitor closely

Key Points:

• ACE inhibitors may cause acute deterioration of renal function in patients with bilateral renal artery stenosis or stenosis of a solitary kidney

• Expect mild rise in creatinine (up to 30% from baseline) initially; significant rise requires re-evaluation

• Known hypersensitivity to enalapril or any ACE inhibitor

• History of angioedema associated with previous ACE inhibitor therapy

• Hereditary or idiopathic angioedema

• Bilateral renal artery stenosis or stenosis of artery to a solitary kidney

• Pregnancy (all trimesters — fetotoxic)

• Concurrent use with aliskiren in patients with diabetes mellitus or eGFR <60 mL/min/1.73m²

• Concurrent use with sacubitril/valsartan (ARNI) — minimum 36-hour washout required

• Volume depletion or salt depletion (risk of severe first-dose hypotension)

• Aortic stenosis or hypertrophic obstructive cardiomyopathy (reduced cardiac output may not tolerate afterload reduction)

• Pre-existing renal impairment (monitor renal function and potassium)

• Hyperkalaemia or concurrent potassium-sparing diuretics/potassium supplements

• Collagen vascular diseases (SLE, scleroderma) — increased risk of neutropenia

• Elderly patients (increased sensitivity to hypotensive effects)

• Black patients (may have reduced response to ACE inhibitors; higher angioedema risk)

• Major surgery/anaesthesia (may cause hypotension)

• Haemodialysis with high-flux membranes (increased anaphylactoid reaction risk)

Aspect Recommendation

Risk category Contraindicated in all trimesters

First trimester Avoid; associated with cardiovascular and CNS malformations (conflicting data but precautionary avoidance recommended)

Second/Third trimester Absolutely contraindicated — causes fetal renal dysgenesis, oligohydramnios, pulmonary hypoplasia, skeletal deformities, neonatal renal failure, hypotension, death

Preferred alternatives Labetalol, methyldopa, nifedipine (for gestational/chronic hypertension)

If exposure occurred Immediate specialist referral; detailed fetal ultrasound for renal anomalies, oligohydramnios, growth

Monitoring Fetal growth and amniotic fluid volume; neonatal renal function and blood pressure if born after exposure

Aspect Recommendation

Compatibility Generally compatible with breastfeeding

Drug levels in milk Low; enalapril and enalaprilat are detected in breast milk in small amounts

Preferred alternatives Enalapril is acceptable; captopril also acceptable

Recommendations May use during breastfeeding; preterm infants may warrant closer monitoring

Infant monitoring Lethargy, poor feeding, adequate weight gain; theoretical risk of hypotension in neonates

Aspect Recommendation

Starting dose 2.5 mg once daily

Titration Slower titration; increase at 2–4 week intervals

Special considerations Age-related decline in renal function common; calculate/estimate eGFR before dosing

Extra risks First-dose hypotension; orthostatic hypotension leading to falls; hyperkalaemia; acute kidney injury; cognitive effects (rare)

Monitoring Blood pressure (including orthostatic); renal function; potassium within 1–2 weeks of initiation

Drug Interaction Management

Potassium-sparing diuretics (spironolactone, amiloride, eplerenone) Severe hyperkalaemia Avoid in renal impairment; if combined, monitor potassium closely (within 1 week and regularly)

Potassium supplements Hyperkalaemia Avoid unless documented hypokalaemia; monitor potassium

Lithium Increased lithium levels → toxicity Avoid combination if possible; if essential, monitor lithium levels closely and reduce lithium dose

Aliskiren Increased risk of hyperkalaemia, hypotension, and renal impairment Contraindicated in diabetes or eGFR <60 mL/min/1.73m²; avoid in all patients if possible

Sacubitril/Valsartan (ARNI) Increased angioedema risk Do not co-administer; 36-hour washout required before switching

ARBs (dual RAAS blockade) Increased renal impairment, hyperkalaemia, hypotension without benefit Avoid combination except under specialist nephrology/cardiology supervision

Drug Interaction Management

NSAIDs (ibuprofen, diclofenac, naproxen) Reduced antihypertensive effect; increased renal impairment risk; hyperkalaemia Avoid prolonged concurrent use; if necessary, monitor BP, renal function, and potassium

Thiazide diuretics Enhanced hypotensive effect; first-dose hypotension Start enalapril at lower dose (2.5 mg) or temporarily hold diuretic

Loop diuretics (furosemide) Enhanced hypotensive effect Monitor BP and volume status; start enalapril at lower dose

Antidiabetic agents (insulin, sulfonylureas) Enhanced hypoglycaemic effect Monitor blood glucose, especially in first weeks

Trimethoprim / Co-trimoxazole Additive hyperkalaemia risk Monitor potassium within 1 week of starting combination

Allopurinol Increased risk of hypersensitivity reactions and neutropenia Monitor; use with caution

Rifampicin May reduce enalapril efficacy (enzyme induction affecting prodrug conversion) Monitor BP; may need dose adjustment

Anaesthetic agents Enhanced hypotension Inform anaesthetist; may need to hold on day of surgery

• Dry persistent cough (5–20%) — class effect; due to bradykinin accumulation

• Dizziness

• Headache

• Fatigue

• Hypotension (especially first-dose)

• Hyperkalaemia

• Elevated serum creatinine (usually transient)

• Nausea

• Diarrhoea

• Rash

Adverse Effect Clinical Notes

Angioedema Face, lips, tongue, larynx, intestine; may be life-threatening; higher risk in Black patients; discontinue immediately; do not rechallenge with any ACE inhibitor

Severe hypotension Especially first-dose in volume-depleted patients; may require IV fluids

Acute kidney injury Particularly in bilateral renal artery stenosis or severe heart failure; monitor creatinine

Hyperkalaemia (severe) Can cause cardiac arrhythmias; more common with renal impairment or concurrent potassium-sparing agents

Neutropenia / Agranulocytosis Rare; more common in collagen vascular diseases (SLE, scleroderma) or renal impairment; discontinue if WBC falls significantly

Hepatotoxicity Rare; cholestatic jaundice, hepatic failure reported; discontinue if occurs

Stevens-Johnson Syndrome / TEN Very rare; discontinue immediately

Foetotoxicity Severe fetal harm in pregnancy — contraindicated

Action: Discontinue enalapril immediately if angioedema, severe hyperkalaemia, significant renal deterioration, or hypersensitivity reactions occur.

After initiation/dose change BP, serum creatinine, and potassium within 1–2 weeks; earlier (3–5 days) if high-risk (elderly, renal impairment, heart failure on diuretics)

During stable therapy BP at each visit; serum creatinine and potassium every 3–6 months; more frequently if renal impairment or concurrent potassium-affecting drugs

Long-term Annual assessment of renal function; reassess indication and response; monitor for persistent cough

Acceptable creatinine rise: Up to 30% increase from baseline is acceptable; if >30% or progressive, investigate for renovascular disease or withhold/reduce dose.

• Enam (USV)

• Envas (Cipla)

• Vasopril (Torrent)

• Enalil (Sun Pharma)

• Enace (Zydus)

• Enacard (Wockhardt)

• Multiple generic manufacturers

• Listed in NLEM 2022

• Under NPPA price ceiling for scheduled formulations

• Available through government supply at public health facilities

1. Prodrug requiring hepatic activation — enalapril is converted to active enalaprilat by liver esterases; in severe hepatic impairment, consider lisinopril (not a prodrug) as alternative.

1. Dry cough is class effect — occurs in 5–20% of patients due to bradykinin accumulation; if intolerable, switch to ARB (losartan, telmisartan) rather than another ACE inhibitor.

1. First-dose hypotension prevention — withhold diuretics for 2–3 days before starting enalapril in volume-depleted patients or start at 2.5 mg with first dose at bedtime.

1. Check renal function and potassium early — monitor within 1–2 weeks of initiation or dose change; accept up to 30% rise in creatinine as expected; >30% rise requires investigation.

1. Target evidence-based doses in heart failure — uptitrate to target dose (10–20 mg twice daily) as tolerated; subtherapeutic doses provide suboptimal benefit.

1. Avoid NSAIDs — concurrent NSAID use reduces antihypertensive efficacy and increases renal impairment and hyperkalaemia risk; particularly important in heart failure and CKD patients.

1. 36-hour washout before ARNI — if switching from enalapril to sacubitril/valsartan, wait minimum 36 hours to reduce angioedema risk.

enalapril; ACE inhibitor; hypertension; heart failure; HFrEF; left ventricular dysfunction; post-MI; diabetic nephropathy; CKD; renal-adjust; pregnancy-contraindicated; NLEM India; Schedule H

RxIndia v1.0 — 26 May 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• NLEM 2022

• API Textbook of Medicine

• Cardiological Society of India (CSI) Guidelines on Heart Failure

• Indian Society of Nephrology Practice Guidelines

• AIIMS Adult Treatment Protocols

• IAP Guidelines (Paediatric Hypertension)

• SOLVD, CONSENSUS trials (for heart failure dosing)

• RENAAL, IDNT trials (for off-label nephropathy indication — class effect)