Pyrazinamide 💊
Related Subjects:
|Tuberculosis
|Isoniazid
|Rifampicin
|Ethambutol
💊 Pyrazinamide is one of the four first-line anti-tuberculosis drugs (RIPE: rifampicin, isoniazid, pyrazinamide, ethambutol). It is given for the first 2 months (initial phase) and allows standard therapy to be shortened to 6 months.
📖 About
- Sterilising activity against semi-dormant intracellular bacilli in acidic environments (macrophage phagolysosomes, caseous lesions).
- Prescribed by TB specialists (NICE NG33); fixed-dose combinations (e.g. Rifater) are available.
- Always check the BNF for up-to-date prescribing information.
⚙️ Mode of Action
- Prodrug converted by mycobacterial pyrazinamidase to pyrazinoic acid, which disrupts membrane energetics and transport at acidic pH.
- Active only against *M. tuberculosis* - not *M. bovis* (intrinsically resistant).
🎯 Indications
- Active TB (pulmonary and extrapulmonary, including TB meningitis) - initial 2-month phase with rifampicin, isoniazid and ethambutol.
- Some multidrug-resistant TB regimens (specialist).
💊 Dose (adult, once daily)
| Body weight | Daily dose |
|---|
| <50 kg | 1.5 g once daily |
| ≥50 kg | 2 g once daily |
| Supervised intermittent regimens (DOT) | Weight-based three-times-weekly dosing per specialist protocol |
- Usual duration: 2 months (initial phase); longer for TB meningitis or as directed.
- Renal impairment: if eGFR <30, give three times weekly per specialist advice (accumulates).
🧪 Monitoring
- Baseline LFTs, renal function, urate, FBC; HIV, hepatitis B and C screening for all TB patients.
- Repeat LFTs if there are symptoms or if there is pre-existing liver disease, alcohol excess or abnormal baseline results.
- Advise patients to report nausea, vomiting, abdominal pain, malaise or jaundice immediately (hepatotoxicity).
🔄 Interactions
- Additive hepatotoxicity with rifampicin, isoniazid, alcohol and other hepatotoxic drugs.
- Antagonises uricosurics (probenecid) and raises urate.
- Ciclosporin levels may fall.
⚠️ Cautions
- Gout - raises urate; avoid in acute gout.
- Diabetes - blood glucose may be harder to control.
- Hepatic impairment (monitor closely); renal impairment.
- Pregnancy: WHO and UK guidance support its use in pregnancy when needed.
🚫 Contraindications
- Severe hepatic impairment.
- Acute porphyria.
- Hypersensitivity.
💥 Side Effects
- Hepatotoxicity (dose-related; can be severe) - the most important.
- Hyperuricaemia, arthralgia and acute gout.
- Nausea, vomiting, anorexia.
- Rash, photosensitivity, fever.
- Rare: sideroblastic anaemia, thrombocytopenia, dysuria, interstitial nephritis.
📚 References
