isoniazid + pyrazinamide + rifampicin: clinical use

Prescribing considerations

• Specialist-supervised, prescription-only fixed combination licensed for pulmonary tuberculosis.
• Confirm that the fixed ratio is appropriate where individual components may require adjustment.
• Review liver and kidney disease, alcohol use, diabetes, HIV, nutritional status, gout, epilepsy, psychosis, neuropathy, porphyria and haemoptysis.
• Complete an interaction check before starting and when stopping treatment.
• Consider pyridoxine for patients at increased risk of isoniazid-related neuropathy.

Contraindications and cautions

• Hypersensitivity to an active substance or excipient
• Current jaundice
• Concurrent saquinavir/ritonavir
• Concurrent lurasidone
• Concurrent sofosbuvir, daclatasvir or telaprevir
• Concurrent cabotegravir, fostemsavir or lenacapavir

Monitoring

• Before treatment: hepatic enzymes, bilirubin, serum creatinine, full blood count and platelet count.
• Assess regularly for adverse-effect symptoms and adherence.
• Repeat liver tests when clinically indicated, with closer monitoring where hepatic risk is increased.
• Monitor urate-related symptoms, neuropathy, blood abnormalities, renal injury and clinically important interacting medicines.

Clinical pharmacology

All three components are bactericidal against tuberculosis. Rifampicin inhibits DNA-dependent RNA polymerase; isoniazid disrupts mycobacterial cell-wall synthesis; and pyrazinamide is active intracellularly in acidic environments. Rifampicin is a potent enzyme and transporter inducer, while isoniazid inhibits selected CYP pathways and has a genetically variable acetylation rate.

Formulation and product differences

• Fixed-ratio, light-pink, round, sugar-coated oral tablet.
• Contains sucrose and is described as essentially sodium-free.
• The fixed component ratio may not be appropriate for children; specialist assessment is required.