Schedule H

Oral

• Capsule (Immediate-release): 5 mg, 10 mg

• Tablet (Sustained-release/Retard): 10 mg, 20 mg

• Tablet (Extended-release/XL/LA): 30 mg, 60 mg

Note: Injectable formulation is NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Essential Hypertension

Sustained-Release/Extended-Release Formulation (Preferred)

Step Dose Clinical Notes

Starting dose 20 mg SR once daily OR 30 mg XL once daily Take with or without food; swallow whole

Titration Increase by 10–20 mg every 7–14 days based on BP response Assess for oedema, flushing before each increment

Usual maintenance dose 30–60 mg once daily May give SR formulation twice daily if needed

Maximum dose 90 mg/day (as XL) OR 60 mg twice daily (as SR)

Key points:

• NEVER use immediate-release for chronic hypertension management — associated with increased cardiovascular mortality

• Extended-release formulations preferred over SR for once-daily dosing

• Monitor for ankle oedema — common but benign; does not respond to diuretics

1. Chronic Stable Angina (Effort Angina)

Sustained-Release/Extended-Release Formulation

Step Dose Clinical Notes

Starting dose 20 mg SR twice daily OR 30 mg XL once daily May combine with beta-blocker for better effect

Titration Increase by 10–20 mg every 7 days based on symptom control Assess exercise tolerance

Usual maintenance dose 30–60 mg/day

Maximum dose 90 mg/day

Key points:

• Alternative to beta-blockers in patients with contraindications (asthma, bradycardia)

• May be used as add-on to beta-blocker for refractory symptoms

• Monitor for reflex tachycardia — less common with SR/XL formulations

1. Vasospastic (Prinzmetal's) Angina

Immediate-Release OR Sustained-Release Formulation

Step Dose Clinical Notes

Starting dose 10 mg TID (immediate-release) OR 20 mg SR BD Immediate-release acceptable in this indication

Titration Increase every 3–7 days based on symptom response

Usual maintenance dose 10–20 mg TID OR 30–60 mg SR daily

Maximum dose 60 mg/day (immediate-release) OR 90 mg/day (SR)

Key points:

• Calcium channel blockers are drugs of choice for vasospastic angina

• Long-acting nitrates may be added if inadequate response

• Avoid beta-blockers (may worsen coronary vasospasm)

1. Severe Hypertension in Pregnancy / Pre-Eclampsia (Acute Control)

Immediate-Release Capsule (Oral)

Step Dose Clinical Notes

Starting dose 10 mg oral (swallowed; NOT sublingual) For SBP ≥160 OR DBP ≥110 mmHg

Titration Repeat 10 mg after 30 minutes if BP not controlled Monitor BP every 15 minutes

Usual maintenance dose Not applicable — switch to oral maintenance after acute control Use methyldopa or labetalol for maintenance

Maximum dose 30 mg in first hour; 120 mg/24 hours

Key points:

• Standard acute antihypertensive in Indian obstetric practice (MoHFW, FOGSI protocols)

• Do NOT bite/puncture capsule or give sublingually — unpredictable absorption and risk of severe hypotension

• Alternative to IV labetalol when IV access/monitoring limited

• Monitor fetal heart rate during acute BP lowering

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Raynaud's Phenomenon 10 mg immediate-release TID OR 30 mg SR daily; may increase to 60 mg/day During cold season or ongoing OFF-LABEL; Specialist (Rheumatology) only; Evidence: Cochrane meta-analysis; Indian rheumatology practice

Tocolysis in Preterm Labour (24–34 weeks) Loading: 20 mg oral stat; then 10–20 mg every 4–6 hours Up to 48 hours (to allow antenatal corticosteroids) OFF-LABEL; Obstetric specialist only; Maximum 160 mg/day; Evidence: Indian obstetric protocols; second-line to atosiban/indomethacin

Anal Fissure (adjunct) 20 mg SR twice daily 6–8 weeks OFF-LABEL; Specialist only; Alternative to GTN ointment; Evidence: Limited RCTs

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not approved for routine paediatric use in India.

Secondary Indications — Paediatrics (Off-label)

Indication Dose Clinical Notes

Hypertensive Urgency/Emergency 0.25–0.5 mg/kg/dose orally every 4–6 hours OFF-LABEL; Maximum 3 mg/kg/day or 60 mg/day; Paediatric nephrology/cardiology specialist only

Chronic Hypertension 0.25–0.5 mg/kg/dose TID (immediate-release) OR equivalent SR dosing OFF-LABEL; Maximum 3 mg/kg/day; Evidence: IAP Nephrology consensus; limited Indian data

Safety monitoring:

• Blood pressure and heart rate with each dose

• Monitor for flushing, headache, dizziness

• Watch for excessive hypotension in volume-depleted children

Minimum age: Not recommended below 1 year of age except under paediatric nephrology/cardiology supervision in critical situations

Notes:

• Nifedipine is primarily hepatically metabolised

• Safe in mild to severe CKD and dialysis patients

• Not removed by haemodialysis or peritoneal dialysis

• May provide renal protection through reduction of intraglomerular pressure

Note: Nifedipine undergoes extensive first-pass hepatic metabolism; bioavailability significantly increased in liver disease

• Known hypersensitivity to nifedipine or any dihydropyridine CCB

• Cardiogenic shock

• Severe aortic stenosis (risk of cardiovascular collapse)

• Unstable angina or acute myocardial infarction (for immediate-release formulation)

• Acute porphyria

• Concurrent use with rifampicin (profound reduction in nifedipine efficacy)

• Use of immediate-release formulation for chronic hypertension management (associated with increased CV mortality)

• Hypotension or low cardiac reserve — may worsen

• Severe left ventricular dysfunction (LVEF <30%) — use with caution

• Diabetes mellitus — may affect glucose control

• Elderly patients — increased sensitivity to hypotensive effects

• Hepatic impairment — reduced clearance

• GI obstruction or stricture — avoid extended-release formulations (non-deformable shell)

• Concurrent beta-blocker use — additive negative inotropic effect possible (though combination generally safe)

• Portal hypertension — may worsen oesophageal varices bleeding risk (theoretical)

Parameter Recommendation

Safety category Generally considered SAFE; extensive experience in Indian obstetric practice

Preferred alternatives Methyldopa (for chronic control); Labetalol IV (for acute severe hypertension if IV access available)

When it may be used Acute severe hypertension in pre-eclampsia/eclampsia (first-line oral agent); tocolysis (off-label but widely used)

Monitoring Maternal: BP (every 15 min during acute use), heart rate, symptoms of hypotension; Fetal: Continuous heart rate monitoring during acute BP lowering

Notes:

• Oral nifedipine is standard of care for acute severe hypertension in pregnancy per MoHFW/FOGSI guidelines

• For tocolysis, use with caution with magnesium sulphate (additive hypotension and neuromuscular blockade)

• Swallow capsule whole — do NOT bite, puncture, or give sublingually

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low (infant receives <5% of maternal weight-adjusted dose)

Preferred alternatives Amlodipine may be preferred for chronic hypertension (once-daily, longer data)

Infant monitoring Observe for poor feeding, excessive sedation (rare); routine monitoring usually sufficient

• Recommended starting dose: 10 mg SR once daily OR 30 mg XL once daily (lower than standard adult)

• Titration: Slower titration intervals (every 2–3 weeks); smaller increments

• Additional risks:

• Increased susceptibility to postural hypotension — fall risk

• Peripheral oedema more pronounced

• Flushing and headache may be more bothersome

• Gingival hyperplasia with chronic use

• May have reduced hepatic clearance

• Monitoring: Standing and supine BP at each visit; assess for oedema

Drug Interaction Management

Rifampicin Potent CYP3A4 inducer → reduces nifedipine levels by 70–90% → loss of antihypertensive effect CONTRAINDICATED — do not use together; use alternative antihypertensive (beta-blocker, ACE inhibitor)

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) Marked increase in nifedipine levels → severe hypotension AVOID combination; if essential, reduce nifedipine dose by 50% and monitor closely

Grapefruit juice Inhibits intestinal CYP3A4 → increased nifedipine bioavailability → hypotension AVOID grapefruit consumption during nifedipine therapy

Magnesium sulphate Additive hypotension and neuromuscular blockade Use together with caution (common in obstetric practice); close BP monitoring; have calcium gluconate available

Quinidine Nifedipine reduces quinidine levels; quinidine may increase nifedipine levels Monitor both drugs' effects; adjust doses as needed

Drug Interaction Management

Beta-blockers Additive negative inotropic effect; both lower BP Generally safe and often beneficial combination; monitor for excessive bradycardia or hypotension

Digoxin Nifedipine may increase digoxin levels by 15–45% Monitor digoxin levels; watch for toxicity

Phenytoin/Carbamazepine/Phenobarbital CYP3A4 inducers → reduced nifedipine levels Monitor BP; may need higher nifedipine dose

Other antihypertensives (ACEi, ARBs, diuretics) Additive hypotensive effect Expected and often desired; titrate carefully

Cimetidine Inhibits CYP3A4 → increased nifedipine levels Use H2 blocker alternative (ranitidine, famotidine) or PPI

Simvastatin Nifedipine may increase simvastatin levels Monitor for myopathy; consider pravastatin as alternative

Tacrolimus/Cyclosporine Nifedipine may increase levels of immunosuppressants Monitor levels; adjust immunosuppressant dose as needed

• Peripheral oedema (ankle swelling) — dose-dependent; very common

• Flushing and feeling of warmth

• Headache

• Dizziness

• Palpitations (reflex tachycardia — less common with SR/XL)

• Nausea

• Fatigue

• Constipation (especially with extended-release)

Reaction Action Required

Severe hypotension Stop nifedipine; supine position; IV fluids; if severe, IV calcium gluconate may help

Myocardial ischaemia/infarction (with immediate-release in CAD) Discontinue immediate-release; manage ACS per protocol; this is why IR is contraindicated for chronic use

Reflex tachycardia → Angina exacerbation Consider adding beta-blocker; switch to longer-acting formulation

Gingival hyperplasia (chronic use) Dental hygiene; may need to switch to different antihypertensive class

Stevens-Johnson Syndrome / TEN (very rare) Discontinue immediately; hospitalise

Hepatotoxicity (rare — cholestatic jaundice) Discontinue; monitor LFTs; hepatology referral if severe

After initiation/dose change (1–2 weeks) Blood pressure; heart rate; assess for oedema, flushing, dizziness

Acute obstetric use BP every 15 minutes for first hour; continuous fetal heart rate monitoring

Long-term (every 6–12 months) Blood pressure; assess for oedema; dental examination (gingival hyperplasia); LFTs if symptomatic

Immediate-release:

• Nicardia (J.B. Chemicals)

• Calcigard (Novartis/Sandoz)

• Depin (Zydus)

Sustained-release (SR/Retard):

• Nicardia Retard (J.B. Chemicals)

• Calcigard Retard (Novartis/Sandoz)

• Depin SR (Zydus)

Extended-release (XL/LA):

• Adalat LA (Bayer) — limited availability

• Nicardia XL (J.B. Chemicals)

Note: FDCs with nifedipine are not commonly used or recommended

NLEM status: Nifedipine sustained-release tablet 20 mg is included in NLEM 2022 — ceiling price applicable under NPPA

Government supply: Available through public health facilities

• NEVER use immediate-release for chronic hypertension: Associated with reflex tachycardia and increased cardiovascular mortality in chronic use — reserve for acute indications only (vasospastic angina, acute severe hypertension in pregnancy)

• Swallow, don't bite in pregnancy: Oral immediate-release capsule should be swallowed whole; biting/puncturing or sublingual use causes unpredictable absorption and dangerous hypotension

• Oedema is not fluid overload: Ankle oedema from nifedipine is due to precapillary vasodilation (not fluid retention); does not respond to diuretics — consider switching CCB class (e.g., to amlodipine) or adding ACE inhibitor

• Grapefruit warning: Clinically significant interaction — advise patients to avoid grapefruit juice during nifedipine therapy

• Rifampicin makes nifedipine useless: Combination essentially contraindicated; find alternative antihypertensive for TB patients (beta-blocker, ACE inhibitor)

• XL ghost tablets: Extended-release tablet shell may appear in stool — this is normal (drug already absorbed)

nifedipine; CCB; dihydropyridine; hypertension; angina; vasospastic angina; pregnancy hypertension; pre-eclampsia; tocolysis; CYP3A4 substrate; renal-safe; NLEM India

RxIndia v1.1 — 14 Jun 2025

• CDSCO Approved Product Information

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NLEM 2022 (National List of Essential Medicines)

• MoHFW Guidelines on Hypertensive Disorders in Pregnancy

• FOGSI Good Clinical Practice Recommendations

• AIIMS Obstetric Protocols

• Indian Society of Hypertension Recommendations

• API Textbook of Medicine (11th Edition)

• IAP Guidelines on Paediatric Hypertension (for off-label paediatric use)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Edition)

• Cochrane Review on CCBs for Raynaud's phenomenon (for off-label indication)