Macrozide-4

Isoniazid (150mg) + Rifampicin (225mg) + Ethambutol (400mg) + Pyrazinamide (750mg)
Price: ₹220 - ₹370 for 60 tablets
Mfr: Macleods Pharmaceuticals Ltd. | Form: Tablet

📋 Clinical Overview

A fixed-dose combination (FDC) of four first-line anti-tubercular drugs used in the intensive phase of treatment for newly diagnosed, drug-sensitive pulmonary and extrapulmonary tuberculosis. This specific strength is designed for patients weighing 30-37 kg, as per the Revised National Tuberculosis Control Programme (RNTCP), now known as the National Tuberculosis Elimination Programme (NTEP), weight-band dosing strategy. It simplifies therapy, improves adherence, and reduces the risk of monotherapy and drug resistance.

💊 Dosage & Administration

Adult: As per NTEP weight bands: This specific 4-drug FDC (H150+R225+E400+Z750) is for patients weighing 30-37 kg. Dose: ONE tablet daily, before breakfast. For other weight bands, different FDC strengths are used.

Note: Take on an empty stomach, at least 1 hour before or 2 hours after food, with a full glass of water. Do not break or crush the FDC tablet unless specified (some are dispersible). Adhere strictly to the daily schedule. If a dose is missed, take it as soon as remembered, but if it's almost time for the next dose, skip the missed dose. Do not double dose.

⚠️ Contraindications

  • History of severe hypersensitivity to any component
  • Severe hepatic impairment or active liver disease (relative, requires extreme caution)
  • History of severe adverse reactions like drug-induced hepatitis, thrombocytopenia, or shock from any component
  • Acute gout

🔬 Mechanism of Action

Combination therapy targeting multiple, distinct biochemical pathways in Mycobacterium tuberculosis to achieve bactericidal and sterilizing effects, preventing emergence of resistance.

🤕 Side Effects

  • Orange/red discoloration of urine, sweat, tears, saliva (Rifampicin - harmless)
  • Nausea, vomiting, abdominal discomfort
  • Skin rash, itching
  • Arthralgia (joint pain) due to Pyrazinamide-induced hyperuricemia
  • Peripheral neuropathy (tingling/numbness - Isoniazid)

🤰 Special Populations

Pregnancy: Category C (US FDA). Use only if clearly needed. Rifampicin is teratogenic in animals. Pyrazinamide use in pregnancy is common in WHO/Indian guidelines but debated due to limited safety data. Isoniazid and Ethambutol are considered safer. Benefits of treating active TB outweigh risks. Supplement with Pyridoxine (Vit B6) 25-50 mg/day.

Driving: Generally safe. Caution if dizziness, visual disturbances (Ethambutol), or CNS effects occur.

🔄 Drug Interactions

Ketoconazole, Itraconazole, FluconazoleReduced azole levels due to Rifampicin enzyme induction; treatment failure.Major
Oral Contraceptives, Hormone Replacement TherapyReduced efficacy; risk of pregnancy. Use non-hormonal backup.Major
Warfarin, AcenocoumarolReduced anticoagulant effect; requires frequent INR monitoring and dose adjustment.Major
Antiretroviral Protease Inhibitors (e.g., Lopinavir/r) & NNRTIs (e.g., Nevirapine)Complex bidirectional interactions; Rifampicin drastically reduces levels of many ARVs. Requires expert management in HIV-TB coinfection.Major
Phenytoin, Carbamazepine, ValproateReduced anticonvulsant levels (Rifampicin); increased Isoniazid levels can inhibit Phenytoin metabolism. Monitor levels.Major
Corticosteroids (e.g., Prednisolone)Reduced corticosteroid effect due to increased metabolism.Moderate
DigoxinReduced Digoxin levels.Moderate
Antacids (Aluminum hydroxide)Reduced absorption of Ethambutol and possibly others.Moderate
Acetaminophen (Paracetamol)Increased risk of hepatotoxicity (additive with Isoniazid).Moderate
AlcoholIncreased risk of hepatotoxicity and CNS effects.Major

🔁 Alternatives to Macrozide-4

Same composition (Isoniazid (150mg) + Rifampicin (225mg) + Ethambutol (400mg) + Pyrazinamide (750mg)), different brands:

AKT-4 R-Cinex Rimactazid-EZ Zupass-4