Antituberculous Agents Pregnancy: Use only if clearly necessary — safety in first trimester not established; WHO recommends using pyrazinamide during pregnancy for active TB if benefits outweigh risks; breastfeeding: small amounts excreted in milk — continue breastfeeding

Pyrazinamide

Brand names: Zinamide

Adult dose

Dose: Weight-based: under 50 kg = 1.5 g daily; 50–74 kg = 2 g daily; 75 kg and above = 2.5 g daily

Route: Oral

Frequency: Once daily

Max: 2.5 g/day

Used in first 2 months of standard RIPE TB treatment only — NOT continued into continuation phase. Take with food to reduce GI side effects.

Paediatric dose

Dose: 35 mg/kg once daily mg/kg

Route: Oral

Frequency: Once daily

Max: 2 g/day

Used for initial 2 months of TB treatment; seek specialist paediatric infectious disease opinion

Dose adjustments

Renal

Reduce dose or increase interval in severe renal impairment (eGFR below 30) — pyrazinoic acid metabolite accumulates and causes gouty arthritis; specialist advice required

Hepatic

Avoid in severe hepatic impairment — hepatotoxic; baseline LFTs mandatory; stop if ALT above 5× ULN

Paediatric weight-based calculator

Patient weight (kg)

Used for initial 2 months of TB treatment; seek specialist paediatric infectious disease opinion

Clinical pearls

Role in TB treatment: pyrazinamide is essential in initial 2-month phase of RIPE — acts on slowly dividing and dormant tubercle bacilli in acidic intracellular environments (macrophages); shortens treatment from 9 months to 6 months by sterilising intracellular bacteria; NOT effective at neutral pH
HYPERURICAEMIA: virtually universal — pyrazinoic acid (active metabolite) inhibits urate secretion in renal tubule; serum urate rises predictably; asymptomatic hyperuricaemia does NOT require dose change; TREAT symptomatic gout with NSAIDs or colchicine; allopurinol is LESS EFFECTIVE during pyrazinamide therapy
HEPATOTOXICITY: pyrazinamide is the most hepatotoxic first-line TB drug; combination RIPE additive hepatotoxicity; monitor LFTs monthly during initial phase; stop pyrazinamide alone if ALT rises significantly; can often continue RH after resolution
MHRA / NICE NG33: pyrazinamide used only in initial 2-month phase (2HRZE) then stopped; continuation phase is 4 months of rifampicin + isoniazid (4HR); if pyrazinamide cannot be used, extend total treatment to 9 months
Photosensitivity: advise sunscreen and protective clothing during treatment — photosensitive skin reaction less common than hyperuricaemia but clinically important
Resistance testing: pyrazinamide resistance (pncA gene mutation) requires susceptibility testing; MDR-TB regimens that include pyrazinamide where susceptible — MHRA guidance

Contraindications

Severe hepatic impairment
Acute gout
Known hypersensitivity to pyrazinamide
Acute porphyria

Side effects

Hyperuricaemia and gout (pyrazinoic acid inhibits renal urate secretion — common; treat with allopurinol if symptomatic gout)
Hepatotoxicity (dose-dependent — most hepatotoxic TB drug; monitor LFTs)
Arthralgia (polyarthralgia — related to hyperuricaemia; 40% patients)
Nausea and vomiting
Photosensitivity (sideroblastic anaemia at high doses — rare)

Interactions

Allopurinol (pyrazinamide blocks uricosuric effect of allopurinol — allopurinol less effective during pyrazinamide; urate-lowering agents generally ineffective; joint pain managed with NSAIDs/colchicine instead)
Probenecid (pyrazinamide blocks uricosuric effect)
No significant CYP450 interactions

Monitoring

LFTs (baseline and monthly during 2-month initial phase)
Serum urate (baseline; manage symptomatically if gouty arthritis develops)
Joint pain symptoms (arthralgia — very common; does not usually require stopping)
Monthly sputum smear and culture

Reference: BNFc; BNF 90; NICE NG33; WHO TB Guidelines 2022; BTS TB Guidelines; BMJ Best Practice TB. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

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