1. Clinical & Scientific Overview
Rifampicin (TIP-MED-000339, Reference Code [8.28]-C69) is classified under
Antimicrobials — NTEP Antitubercular Agents (Ch 08) as a National Tuberculosis Elimination Programme (NTEP) Daily Weight-Band 4-FDC & 3-FDC Regimen (Schedule H1 | NLEM 2022 | HIGH-ALERT).
Within the Indian regulatory and compendial framework, it is governed under Schedule H1 Prescription Drug (Mandatory 3-Year Register Retention) • NLEM 2022 Core Essential.
Co-indexed constituent under primary monograph [8.28] (First-Line Anti-Tuberculosis Fixed-Dose Combinations (Isoniazid [H] + Rifampicin [R] + Pyrazinamide [Z] + Ethambutol [E])). Representative Indian Market Examples (Edition 2.7 Ch 08 [8.28], p. 106): NTEP Free Govt Supply; Retail 4-FDC (HRZE): Akurit-4 (Lupin), Forecox (Macleods), Rimstar 4-FDC, AKT-4 Kit. Retail 3-FDC (HRE): Akurit-3, Forecox-3 — Strengths & Forms: Adult Standard 4-FDC Tablet (Intensive Phase): Isoniazid 75 mg + Rifampicin 150 mg + Pyrazinamide 400 mg + Ethambutol 275 mg. Adult Standard 3-FDC Tablet (Continuation Phase): H 75 + R 150 + E 275 mg
Adult Standard 4-FDC Tablet (Intensive Phase): Isoniazid 75 mg + Rifampicin 150 mg + Pyrazinamide 400 mg + Ethambutol 275 mg. Adult Standard 3-FDC Tablet (Continuation Phase): H 75 + R 150 + E 275 mg
3. Mechanism of Action & Pharmacodynamics
Dual synergistic mycobactericidal action: (1) Rifampicin binds the beta-subunit (rpoB gene) of bacterial DNA-dependent RNA polymerase, sterically blocking RNA chain initiation and killing both intracellular and semi-dormant persister bacilli; (2) Isoniazid (prodrug activated by mycobacterial catalase-peroxidase KatG) forms an INH-NAD adduct that inhibits Enoyl-ACP reductase (InhA), blocking synthesis of mycolic acids essential for the mycobacterial cell wall.
4. Therapeutic Indications & Evidence-Supported Uses
- Drug-sensitive pulmonary and extrapulmonary Tuberculosis (Intensive Phase 2HRZE + Continuation Phase 4HRE under India's NTEP daily weight-band FDC regimen)
5. Educational Dosage Context, Formulations & Administration
Educational Dosing & Regimen Summary: NTEP Adult Daily Weight-Band FDCs: ~10 mg/kg Rifampicin (max 600 mg) + ~5 mg/kg Isoniazid (max 300 mg) once daily on an empty stomach, supplemented with Pyridoxine (Vitamin B6) 10–50 mg/day.
Administration & Meal Timing: Oral; take once daily on an empty stomach (1 hour before or 2 hours after breakfast).
6. Pharmacokinetics, Metabolism & Renal/Hepatic Adjustment
Follows class pharmacokinetic profile detailed in parent monograph [8.28].
High risk of Drug-Induced Liver Injury (DILI); hold both drugs immediately if ALT/AST > 5x ULN (asymptomatic) or > 3x ULN with jaundice/hepatitis symptoms.
No dose adjustment required for Rifampicin or Isoniazid at standard daily doses in CKD.
High risk of Drug-Induced Liver Injury (DILI); hold both drugs immediately if ALT/AST > 5x ULN (asymptomatic) or > 3x ULN with jaundice/hepatitis symptoms.
7. Contraindications, Precautions & High-Risk Warnings
- Acute active hepatitis or severe drug-induced jaundice
- Concomitant protease inhibitors, Doravirine, Rilpivirine, Praziquantel, or Voriconazole (profound CYP3A4 induction by Rifampicin destroys efficacy)
Key Clinical Precautions: High risk of Drug-Induced Liver Injury (DILI); hold both drugs immediately if ALT/AST > 5x ULN (asymptomatic) or > 3x ULN with jaundice/hepatitis symptoms.
8. Adverse Effects Profile
- Drug-Induced Liver Injury (DILI — additive transaminitis and hepatitis from both INH and Rifampicin)
- Isoniazid-induced peripheral neuropathy (glove-and-stocking paraesthesia due to pyridoxal-5-phosphate depletion — prevented by Vitamin B6 10–50 mg/day)
- Harmless orange-red discolouration of urine, sweat, saliva, and tears (permanently stains soft contact lenses)
- Rifampicin flu-like syndrome, thrombocytopenia, and drug-induced lupus (INH)
9. Major Drug–Drug, Drug–Food & Drug–Herb Interactions
- Oral Contraceptives, Warfarin, Phenytoin, Cyclosporine, Tacrolimus, Methadone, Corticosteroids, Sulfonylureas, Dolutegravir: Rifampicin potently induces CYP3A4/2C9/2C19/P-gp (Dolutegravir must be doubled to 50 mg BD; women must use non-hormonal/barrier contraception)
- Phenytoin & Carbamazepine: Isoniazid inhibits CYP2C19/3A4 and precipitates Phenytoin toxicity (ataxia, nystagmus)
- Alcohol & Paracetamol: markedly increases risk of severe hepatotoxicity
10. Clinical Monitoring, Patient Counselling & Storage
Clinical & Laboratory Monitoring: Monitor clinical parameters per parent monograph [8.28].
Pharmacist Patient Counselling Points:
- Urine, sweat, and tears will turn orange-red — this is completely expected and harmless, but avoid wearing soft contact lenses.
- Always take daily Pyridoxine (Vitamin B6) alongside Isoniazid to prevent numbness or tingling in hands and feet.
- Avoid alcohol completely and report yellow eyes, dark cola urine, or persistent nausea/vomiting immediately.
Storage, Stability & Dispensing Safeguards: Store below 25–30°C in moisture-barrier blisters (Rifampicin-INH FDCs form inactive isonicotinyl hydrazone if exposed to heat/humidity).
11. Visual Pharmacology & Mechanism Diagram (svg-v339-01-adme-12-step-journey)
12. Authoritative References, Regulatory Sources & Editorial Disclaimer
Primary Compendial & Guideline Reference: Indian Pharmacopoeia (IP 2022) • NFI • CDSCO
Official Verification Portals: Indian Pharmacopoeia Commission (IPC) & National Formulary of India (NFI) • Central Drugs Standard Control Organization (CDSCO) • Ministry of Health & Family Welfare — NLEM 2022 • NCBI Bookshelf / StatPearls Pharmacology Reference • DailyMed (US FDA Official Prescribing Reference)
Last Medically & Pharmaceutically Reviewed: 2026-11-10 • Verification Status: VERIFIED_EDUCATIONAL_CONTENT
Educational & Clinical Disclaimer: This reference profile is published solely for pharmacy education, academic study, and professional clinical reference. It does not substitute for patient-specific clinical judgement, qualified specialist oncology/medical supervision, or official CDSCO/IP prescribing information. Never self-medicate with prescription, Schedule H/H1/X, NDPS, or oncology medicines.