Rifampicin with ethambutol, isoniazid and pyrazinamide

How it works

Rifampicin inhibits bacterial RNA polymerase, isoniazid blocks mycolic acid synthesis, pyrazinamide is active against semi-dormant bacilli in acidic environments, and ethambutol inhibits arabinosyl transferase to impair cell-wall synthesis — together attacking different mycobacterial populations and reducing resistance.

Prescribing in practice

• Rifampicin, isoniazid and pyrazinamide are all potentially hepatotoxic — check baseline liver function, monitor during treatment, and warn patients to report symptoms of hepatitis promptly.
• Ethambutol can cause dose-related optic neuritis, so assess visual acuity and colour vision at baseline and advise patients to report any visual change; the combination is unsuitable when individual dose adjustment (for example in renal impairment) is required.
• Rifampicin is a potent enzyme inducer that reduces the efficacy of many drugs including hormonal contraception, and pyridoxine is co-prescribed to prevent isoniazid-induced peripheral neuropathy.

Monitoring

Monitor liver function and clinical wellbeing during treatment, with baseline and ongoing assessment of visual function because of the ethambutol component and renal function to confirm the fixed combination is appropriate.

Counselling the patient

• Take the tablets as a single daily dose, usually before food, and do not stop without advice — completing the full course is essential.
• 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, or any change in your vision or colour perception.

Evidence & guidelines

Fixed-dose combination therapy is recommended in NICE tuberculosis guidance to support adherence and reduce the risk of acquired drug resistance during the intensive phase.