This combination is indicated for the treatment of both pulmonary and extrapulmonary tuberculosis during the intensive initial phase of therapy.

Rifampicin: Rifampicin is a semisynthetic derivative of rifamycin. It suppresses bacterial RNA synthesis by binding to the beta-subunit of DNA-dependent RNA polymerase, thereby preventing the enzyme from attaching to DNA and inhibiting RNA transcription and elongation. It does not inhibit the corresponding enzyme in mammalian cells. Rifampicin has bactericidal activity and a strong sterilizing effect against both intracellular and extracellular tubercle bacilli. Cross-resistance has been demonstrated only with other rifamycin derivatives.

Isoniazid: Isoniazid kills actively growing tubercle bacilli by inhibiting the biosynthesis of mycolic acids, which are major components of the cell wall of Mycobacterium tuberculosis.

Pyrazinamide: Pyrazinamide is an antituberculous agent and a pyrazine analogue of nicotinamide. Its exact mechanism of action is not fully known. Its metabolite, pyrazinoic acid, which is less active in vitro, may contribute to the drug’s activity in vivo.

Ethambutol: Ethambutol penetrates slowly into actively growing mycobacterial cells, including tubercle bacilli. It inhibits the synthesis of one or more metabolites, leading to disruption of cellular metabolism, arrest of cell multiplication, and eventual cell death. No cross-resistance with other antituberculous agents has been demonstrated.

Spectrum of Activity: At therapeutic concentrations, rifampicin, isoniazid, pyrazinamide, and ethambutol have demonstrated bactericidal activity against both intracellular and extracellular Mycobacterium tuberculosis.

Adults: 3 tablets/day for an average body weight of 50 kg.

Patients weighing-

• >70 kg: 5 tablets
• 55-70 kg: 4 tablets
• 38-54 kg: 3 tablets
• 30-37 kg: 2 tablets

All doses to be taken once daily for 2 months on intensive phase.

Rifampicin: Rifampicin induces microsomal enzymes and may accelerate the clearance of several drugs, including methadone, oral anticoagulants, glucocorticoids, estrogens, oral hypoglycaemic agents, digitoxin, antiarrhythmics, theophylline, anticonvulsants, azole antifungals, and cyclosporin.

Isoniazid: Isoniazid may inhibit the metabolism of antiepileptic drugs, benzodiazepines, warfarin, and theophylline. It may also increase the metabolism of enflurane. Interactions may also occur with alcohol, aspirin (ASA), aluminum-containing antacids, corticosteroids, ketoconazole, and propranolol.

Pyrazinamide: Pyrazinamide may reduce the effectiveness of medicines used for the treatment of gout.

Ethambutol: Ethambutol should be used with caution with other neurotoxic agents, as this may increase the risk of nerve-related adverse effects.

This combination is contraindicated in patients with hypersensitivity to rifampicin, isoniazid, pyrazinamide, or ethambutol.

Isoniazid-related contraindications: Isoniazid is contraindicated in patients with a history of isoniazid-associated liver injury, severe adverse reactions to isoniazid such as fever, chills, and arthritis, acute liver disease of any cause, or a previous hypersensitivity reaction to isoniazid, including drug-induced hepatitis.

Rifampicin: Rifampicin may cause reddish discoloration of body fluids, asymptomatic elevation of liver enzymes, and increases in blood urea nitrogen (BUN) and uric acid levels. Other reported effects include hemolysis, hematuria, interstitial nephritis, renal insufficiency, gastrointestinal discomfort, central nervous system effects, hematological changes, skin rash, and endocrine disturbances.

Isoniazid: Isoniazid may cause abnormal liver function, hepatitis, gastrointestinal disturbances, peripheral neuropathy, dizziness, lightheadedness, hematological changes, and allergic reactions.

Pyrazinamide: Pyrazinamide may cause a temporary increase in serum transaminases, hepatotoxicity, hepatomegaly, jaundice, hyperuricemia, interstitial nephritis, dysuria, gastrointestinal disturbances, hematological changes, and allergic reactions.

Ethambutol: Ethambutol may cause confusion, disorientation, headache, visual disturbances, jaundice, transient liver dysfunction, gastrointestinal disturbances, hematological changes, allergic reactions, and, rarely, acute gout.

Rifampicin: Rifampicin has been reported to cross the placental barrier and may be found in cord blood and maternal milk. Therefore, newborns and infants of mothers treated with rifampicin should be carefully monitored for any possible adverse effects.

Ethambutol: Although the use of ethambutol in pregnant women has not shown any detectable harmful effect on the fetus, the possible teratogenic risk in women of childbearing potential should be carefully weighed against the expected benefits of treatment.

This medicine should be used with caution in patients with impaired renal or hepatic function, diabetes mellitus, chronic alcoholism, undernourishment, a history of gout, convulsive disorders, or acute porphyria. Special caution is also advised in elderly patients, as well as during pregnancy and lactation. Periodic blood counts and liver function tests should be performed during treatment. Patients should also avoid using soft contact lenses while taking this medicine.

In children younger than 8 years and in patients who are unable to report visual symptoms, special caution is required because visual disturbances may not be easily recognized. Visual acuity should be assessed before starting treatment and monitored regularly during therapy.

Use in Children: Ethambutol is not recommended for children under 13 years of age, as safe conditions for its use have not been fully established.

Combined anti-tubercular preparations

Store at a temperature not exceeding 30°C.