Schedule H

Oral, Intravenous

Formulation Strength

Tablets 150 mg, 300 mg, 450 mg, 600 mg

Capsules 150 mg, 300 mg, 450 mg

Oral suspension (paediatric) 100 mg/5 mL

Injection (lyophilised powder) 600 mg per vial

Fixed-Dose Combinations (FDCs) available:

• Rifampicin + Isoniazid (various strengths)

• Rifampicin + Isoniazid + Pyrazinamide (various strengths)

• Rifampicin + Isoniazid + Pyrazinamide + Ethambutol (various strengths)

• Paediatric dispersible FDCs available under NTEP

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Pulmonary and Extrapulmonary Tuberculosis

As part of multi-drug regimen per NTEP guidelines. Never use as monotherapy.

Parameter Recommendation

Starting dose 10 mg/kg orally once daily (empty stomach, 1 hour before or 2 hours after meals)

Titration Not applicable (weight-band based fixed dosing)

Usual maintenance dose 10 mg/kg once daily

Maximum dose 600 mg/day

Weight-Band Dosing for Adults (NTEP Guidelines):

Body Weight Daily Rifampicin Dose

30–39 kg 450 mg once daily

40–54 kg 450 mg once daily

55–69 kg 600 mg once daily

≥70 kg 600 mg once daily

Duration per NTEP:

• New cases: 2 months intensive phase (HRZE) + 4 months continuation phase (HR)

• Previously treated: As per drug susceptibility testing

• Extrapulmonary TB (bone, CNS): Extended duration (9–12 months) per site

Clinical Notes:

• Preferably use fixed-dose combinations (FDCs) to ensure adherence

• Administer all drugs together as single daily dose

• IV route reserved for patients unable to take oral medications

1. Latent Tuberculosis Infection (LTBI)

Per ICMR/NTEP preventive therapy guidelines.

Regimen Options:

Regimen Dose Duration

3HR (Rifampicin + Isoniazid) Rifampicin 10 mg/kg (max 600 mg) + INH 5 mg/kg (max 300 mg) once daily 3 months

4R (Rifampicin monotherapy) 10 mg/kg once daily (max 600 mg) 4 months

Clinical Notes:

• Rule out active TB before initiating preventive therapy

• Monitor LFTs at baseline and during therapy

• Indicated for close contacts, immunocompromised, HIV-positive individuals

1. Leprosy (Hansen's Disease)

As part of Multi-Drug Therapy (MDT) per NLEP guidelines.

Leprosy Type Rifampicin Dose Frequency Duration

Paucibacillary (PB) 600 mg Once monthly (supervised) 6 months

Multibacillary (MB) 600 mg Once monthly (supervised) 12 months

Clinical Notes:

• Monthly dose is directly observed/supervised

• Given in combination with dapsone (PB) or dapsone + clofazimine (MB)

• Rifampicin is the most bactericidal component of MDT

1. Brucellosis

In combination with doxycycline.

Parameter Recommendation

Starting dose 600 mg orally once daily (or 15 mg/kg)

Titration Not applicable

Usual maintenance dose 600–900 mg once daily

Maximum dose 900 mg/day

Duration: 6 weeks minimum (with doxycycline 100 mg BD)

Clinical Notes:

• Combination therapy mandatory to prevent relapse

• Alternative: Rifampicin + streptomycin for complicated cases

1. Meningococcal Meningitis Chemoprophylaxis

For close contacts of confirmed Neisseria meningitidis cases.

PAEDIATRIC DOSING (Specialist Only)

⚠️ Always use in combination therapy for TB and leprosy — monotherapy causes rapid resistance.

⚠️ Paediatric dispersible FDCs preferred under NTEP for children <25 kg.

Primary Indications (Approved/Standard Use in India)

1. Tuberculosis (Pulmonary and Extrapulmonary)

Weight-Band Dosing per NTEP/IAP Guidelines:

Weight Band Rifampicin Dose (Once Daily)

4–7 kg 75 mg

8–11 kg 150 mg

12–15 kg 225 mg

16–24 kg 300 mg

25–29 kg 375 mg

30–39 kg 450 mg

≥40 kg 600 mg (adult dosing)

General Paediatric Dosing:

• Starting dose: 10–20 mg/kg once daily

• Titration: Not applicable

• Usual maintenance dose: 15 mg/kg once daily

• Maximum dose: 600 mg/day

Duration:

• Drug-susceptible TB: 6 months (2HRZE + 4HR)

• TB meningitis/bone TB: 12 months

Clinical Notes:

• Use paediatric dispersible FDC tablets for children <25 kg

• Oral suspension (100 mg/5 mL) available for precise dosing in infants

• Administer on empty stomach; can mix with small amount of water/milk if needed

1. Leprosy (MDT in Children)

10–14 years 450 mg Once monthly (supervised)

<10 years 10 mg/kg Once monthly (supervised)

1. Latent TB Infection (LTBI) Preventive Therapy

Parameter Recommendation

Starting dose 10–20 mg/kg once daily

Titration Not applicable

Usual maintenance dose 15 mg/kg once daily

Maximum dose 600 mg/day

Duration: 4 months (4R regimen) or 3 months with isoniazid (3HR)

Eligibility: Age ≥2 years; younger children under specialist supervision only

Secondary Indications – Paediatrics (Off-label)

Indication Dose Duration Notes

Meningococcal prophylaxis 10 mg/kg (max 600 mg) every 12 hours 2 days (4 doses) OFF-LABEL for age <1 month; Children ≥1 month: standard use; Evidence: ICMR/CDC recommendations

Haemophilus influenzae type b prophylaxis 20 mg/kg once daily (max 600 mg) 4 days OFF-LABEL; Household contacts; Evidence: IAP/CDC guidelines

Age Restrictions:

• Neonates (<1 month): Use only under specialist supervision for TB exposure or specific prophylaxis indications

• Oral suspension preferred for accurate dosing in infants and young children

Safety Monitoring in Paediatrics:

• Baseline LFTs before starting therapy

• Clinical monitoring for jaundice, hepatomegaly, vomiting

• Repeat LFTs if symptomatic or at 2 weeks in high-risk children

• Weight monitoring for dose adjustments

Drug-Induced Liver Injury (DILI) Management:

• If ALT >5× ULN (asymptomatic) or >3× ULN with symptoms: Stop rifampicin

• Rechallenge only after LFTs normalise; reintroduce at reduced dose with close monitoring

• Known hypersensitivity to rifampicin or other rifamycins (rifabutin, rifapentine)

• Concurrent use with HIV protease inhibitors (ritonavir, lopinavir, atazanavir, darunavir) — contraindicated due to severe reduction in PI levels

• Concurrent use with delavirdine — contraindicated

• Jaundice or acute hepatitis at time of planned initiation

• Previous severe hepatotoxicity attributed to rifampicin

• Pre-existing liver disease or chronic hepatitis — increased hepatotoxicity risk

• Chronic alcoholism — additive hepatotoxic potential

• HIV coinfection — multiple ART interactions; consult HIV specialist

• Porphyria — may precipitate attacks

• Concurrent use with other hepatotoxic drugs (pyrazinamide, isoniazid, methotrexate)

• Elderly patients — reduced hepatic reserve; closer monitoring needed

• Women on hormonal contraceptives — rifampicin reduces efficacy; advise barrier methods

• Soft contact lens users — may cause permanent orange staining

• Diabetes mellitus — may require adjustment of oral hypoglycaemic agents

Parameter Recommendation

Risk Category Category C (generally considered safe; benefits outweigh risks for TB)

Overall Recommendation Safe and indicated for tuberculosis treatment throughout pregnancy

Preferred Alternatives No alternative needed; rifampicin is preferred first-line agent for TB in pregnancy

When to use All trimesters; do not defer TB treatment due to pregnancy

Monitoring Maternal LFTs, platelet count; Vitamin K supplementation (10 mg/day) in last 4 weeks to prevent neonatal haemorrhagic disease

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug Levels in Milk Low (1–3% of maternal dose reaches infant)

Preferred Alternatives None needed; continue rifampicin during breastfeeding

Infant Monitoring Observe for jaundice, adequate weight gain; no specific concerns reported

Parameter Recommendation

Starting Dose Standard dose (10 mg/kg/day, max 600 mg)

Titration Not applicable

Special Risks Reduced hepatic reserve — higher hepatotoxicity risk; polypharmacy interactions common (warfarin, antidiabetics, cardiovascular drugs)

Monitoring LFTs at baseline, 2 weeks, and monthly; review concurrent medications for interactions; monitor INR if on warfarin

Interacting Drug Mechanism/Effect Management

HIV Protease Inhibitors (ritonavir, lopinavir, atazanavir, darunavir) Potent CYP3A4 induction → >75% reduction in PI levels Contraindicated; Use rifabutin instead if available

Delavirdine (NNRTI) Marked reduction in delavirdine levels Contraindicated

Warfarin CYP2C9/3A4 induction → reduced warfarin effect → INR drops significantly Increase warfarin dose by 50–100%; monitor INR twice weekly during initiation and after stopping rifampicin

Oral contraceptives CYP3A4 induction → reduced oestrogen/progestogen levels → contraceptive failure Use non-hormonal contraception (barrier methods, copper IUD)

Azole antifungals (ketoconazole, itraconazole, voriconazole) CYP3A4 induction → azole levels reduced by 50–90% Avoid combination; if essential, increase azole dose significantly with TDM

Cyclosporine/Tacrolimus CYP3A4 induction → marked reduction in calcineurin inhibitor levels Increase immunosuppressant dose 2–5 fold; frequent TDM essential

Efavirenz/Nevirapine Reduced NNRTI levels (20–30%) Can be used together; no dose adjustment needed for standard-dose efavirenz (600 mg)

Dolutegravir CYP3A4/UGT induction → reduced DTG levels Increase dolutegravir to 50 mg twice daily during rifampicin use

Interacting Drug Effect Management

Oral antidiabetics (sulfonylureas, metformin, glipizide) Reduced hypoglycaemic effect Monitor blood glucose closely; may need dose increase

Methadone/Buprenorphine Reduced opioid levels → withdrawal symptoms Increase opioid dose; monitor for withdrawal

Phenytoin Variable effect (may increase or decrease levels) Monitor phenytoin levels

Theophylline Increased clearance → reduced levels Monitor theophylline levels; may need dose increase

Beta-blockers (metoprolol, propranolol) Reduced beta-blocker effect Monitor BP and heart rate; adjust dose

Calcium channel blockers (amlodipine, nifedipine, verapamil) Reduced CCB levels Monitor BP; may need dose increase

Corticosteroids (prednisolone, dexamethasone) Reduced steroid effect Double the corticosteroid dose during rifampicin therapy

Clofazimine Possible additive hepatotoxicity Monitor LFTs when used together in MDR-TB regimens

Levothyroxine Increased metabolism Monitor TSH; may need levothyroxine dose increase

• Gastrointestinal: nausea, anorexia, abdominal discomfort, diarrhoea

• Orange-red discoloration of urine, tears, sweat, saliva, sputum (harmless but may stain contact lenses and fabrics permanently)

• Cutaneous: flushing, pruritus, mild rash

• Transient asymptomatic elevation of liver enzymes

• Headache

Adverse Effect Clinical Significance

Hepatotoxicity / Drug-induced hepatitis Can be severe and fatal; stop if ALT >5× ULN or >3× ULN with symptoms (jaundice, nausea, vomiting)

Thrombocytopenia Immune-mediated; may cause purpura, bleeding; stop rifampicin immediately

Haemolytic anaemia Rare; Coombs-positive; discontinue immediately

Acute renal failure Rare; immune-mediated interstitial nephritis; requires discontinuation

Flu-like syndrome Occurs with intermittent or interrupted dosing; fever, chills, myalgia, headache; may require regimen modification

Stevens-Johnson Syndrome / TEN Rare; immediate discontinuation and hospitalisation required

Pseudomembranous colitis Rare; consider if severe diarrhoea develops

After initiation (2–4 weeks) LFTs; earlier if symptomatic or high-risk (HIV, liver disease, alcoholism)

Monthly during intensive phase LFTs, clinical assessment for jaundice, bleeding, rash

Continuation phase LFTs every 1–2 months if asymptomatic; immediate testing if symptoms develop

Drug interaction monitoring INR if on warfarin; blood glucose if diabetic; immunosuppressant levels if applicable

Clinical surveillance Symptoms of hepatitis (anorexia, nausea, dark urine, jaundice), bleeding, fever, rash

Single-Agent Formulations:

• R-CIN® (Lupin)

• RIFADIN® (Sanofi)

• RIMACTANE® (Sandoz)

• TIBIRIM® (Cadila)

• RIFAMYCIN® (Various generics)

Fixed-Dose Combinations (FDCs):

• FORECOX® (4-drug FDC) — Macleods

• MYCOBUTOL-RIF® (Rifampicin + Ethambutol)

• Paediatric dispersible FDCs available through NTEP

Note: Government supply (NTEP) provides FDCs free of cost at designated TB centres.

Regulatory Notes:

• Included in NLEM 2022 (essential medicine for TB)

• Under NPPA price control

• Free supply under NTEP at government facilities and DOTS centres

1. Never monotherapy: Rifampicin must always be used in combination for TB and leprosy — monotherapy leads to rapid resistance development within weeks.

1. Enzyme induction timeline: CYP induction begins within 1–2 days and reaches maximum effect by 1–2 weeks; effects persist for 2–4 weeks after discontinuation — plan drug interaction management accordingly.

1. Orange discoloration counselling: Pre-warn patients about harmless orange-red discoloration of body fluids; advise against soft contact lenses (permanent staining); reassure this indicates drug absorption, not toxicity.

1. HIV-TB coinfection: Rifampicin can be used with efavirenz, nevirapine, or dolutegravir (with dose adjustment). For PI-based ART, substitute with rifabutin if available, or consult HIV specialist.

1. Flu-like syndrome prevention: Occurs primarily with intermittent dosing or treatment interruptions — emphasise adherence; if syndrome occurs, switch to daily supervised therapy.

1. Hepatotoxicity vigilance: Risk is highest in first 2 months; combination with isoniazid and pyrazinamide increases risk — obtain LFTs before and during early treatment; educate patients on warning symptoms.

rifampicin; tuberculosis; antitubercular; leprosy; MDT; CYP3A4 inducer; hepatotoxic; NTEP; NLEM India; drug interactions; pregnancy-compatible

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Product Information

• Indian Pharmacopoeia 2018

• National TB Elimination Programme (NTEP) — Technical and Operational Guidelines (2021)

• ICMR Guidelines on LTBI Management

• NLEP (National Leprosy Eradication Programme) Guidelines

• API Textbook of Medicine (Tuberculosis, Leprosy chapters)

• IAP Guidelines on Paediatric Tuberculosis

• AIIMS Antimicrobial Therapy Protocols

• National AIDS Control Organisation (NACO) — ART Guidelines for HIV-TB Coinfection

• International RCTs/meta-analyses — referenced for off-label indications (cholestatic pruritus, prosthetic joint infections) only