Ethambutol / Isoniazid / Pyrazinamide / Rifampicin

What it is and how it works

Rifampicin inhibits bacterial DNA-dependent RNA polymerase; isoniazid inhibits mycolic acid synthesis in the mycobacterial cell wall; pyrazinamide, active in acidic environments, kills semi-dormant intracellular bacilli; ethambutol inhibits arabinosyl transferases involved in cell-wall arabinogalactan synthesis. The combination is bactericidal and sterilising and prevents emergence of resistance.

Indications

Intensive (initial) phase of treatment of drug-susceptible pulmonary and extrapulmonary tuberculosis in adults, as recommended by WHO and national programmes.

Dosage and administration (summary)

Oral, once daily on an empty stomach, number of tablets according to body-weight bands (for the standard 75/150/400/275 mg tablet, e.g. 3 tablets for 38–54 kg, 4 for 55–70 kg and 5 for 71 kg or more), usually for the first 2 months of treatment.

Contraindications

Hypersensitivity to any component, acute liver disease or severe hepatic impairment, jaundice, acute porphyria, and pre-existing optic neuritis.

Warnings and precautions

Hepatotoxicity may occur, so liver function should be assessed at baseline and monitored in those at risk, and treatment interrupted if hepatitis develops. Ethambutol can cause dose-related optic neuritis, so visual acuity and colour vision should be checked; isoniazid can cause peripheral neuropathy (pyridoxine prophylaxis is recommended in at-risk patients); pyrazinamide raises uric acid. Rifampicin is a potent enzyme inducer with many interactions (including hormonal contraceptives, antiretrovirals and anticoagulants) and colours body fluids orange-red.

Pregnancy

The standard first-line regimen is recommended in pregnancy by WHO, as untreated tuberculosis poses a greater risk; pyridoxine supplementation is advised.

Storage and supply

Store below 30 °C in the original container, protected from light and moisture.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.