Rifampicin with isoniazid and pyrazinamide

How it works

Rifampicin inhibits bacterial RNA polymerase, isoniazid blocks mycolic acid synthesis, and pyrazinamide is active against semi-dormant bacilli in acidic intracellular conditions, together targeting different mycobacterial populations and reducing the emergence of resistance.

Prescribing in practice

• All three components are potentially hepatotoxic, so check baseline liver function, monitor during treatment, and counsel patients to report symptoms of hepatitis promptly.
• Rifampicin is a potent enzyme inducer that reduces the efficacy of many drugs including hormonal contraception, so co-medication must be reviewed; this combination is typically used with ethambutol where indicated.
• Pyridoxine is co-prescribed to prevent isoniazid-induced peripheral neuropathy, and pyrazinamide may raise serum urate and precipitate gout.

Monitoring

Monitor liver function and clinical wellbeing during treatment, and be alert to hyperuricaemia from the pyrazinamide component.

Counselling the patient

• Take the tablets as a single daily dose, usually before food, and complete the entire course.
• Rifampicin turns urine, tears and other body fluids orange-red and can permanently stain soft contact lenses.
• Report promptly any yellowing of the skin or eyes, nausea, loss of appetite or joint pain.

Evidence & guidelines

Fixed-dose combination therapy is recommended in NICE tuberculosis guidance to improve adherence and limit acquired drug resistance during the intensive phase.