Antitubercular — First-Line TB (RIPE Regimen, 'P') Pregnancy: Use with caution — limited data; WHO recommends use in pregnant women with TB when benefit outweighs risk

Pyrazinamide

Brand names: Zinamide

Adult dose

Dose: 15–30 mg/kg once daily (initial 2-month phase only)

Route: Oral

Frequency: Once daily

Max: 2.5 g/day (if <50 kg); 3 g/day (if >50 kg); dose bands per weight: <50 kg: 1.5 g, 51–74 kg: 2 g, >75 kg: 2.5 g

Given only in the initial 2-month phase of TB treatment (not continued in 4-month continuation phase). Active against intracellular mycobacteria in acidic environment of macrophage lysosomes — unique mechanism. Activated to pyrazinoic acid by mycobacterial pyrazinamidase. Essential for shortening TB treatment from 9 to 6 months.

Paediatric dose

Dose: 35 mg/kg mg/kg

Route: Oral

Frequency: Once daily

Max: 2.5 g/day

BNFc: used as part of standard RIPE regimen in children; higher mg/kg dose than adults

Dose adjustments

Renal

CrCl <30 mL/min: reduce to 3x/week dosing; haemodialysis: dose post-dialysis

Hepatic

Contraindicated in severe hepatic impairment — hepatotoxic; use with caution in any hepatic disease

Paediatric weight-based calculator

Patient weight (kg)

BNFc: used as part of standard RIPE regimen in children; higher mg/kg dose than adults

Clinical pearls

Key role: shortens TB treatment from 9 to 6 months by sterilising intracellular organisms — without pyrazinamide, treatment requires 9 months (RIE × 9)
Hyperuricaemia: check baseline uric acid; asymptomatic hyperuricaemia during TB treatment does not require treatment — stop allopurinol if on it; treat only if gout symptoms develop
Hepatotoxicity: most hepatotoxic of the first-line TB drugs when used with rifampicin and isoniazid — check LFTs at 2 weeks, 4 weeks, then monthly; stop if ALT >5× ULN or jaundice develops
Mechanism: converted to pyrazinoic acid by mycobacterial PncA enzyme — disrupts mycobacterial membrane potential and energy production; active in acid pH of macrophage lysosomes

Contraindications

Severe hepatic impairment
Acute gout
Hypersensitivity to pyrazinamide

Side effects

Hepatotoxicity (most significant — monitor LFTs at baseline and monthly)
Hyperuricaemia (blocks renal uric acid excretion — can precipitate gout)
Arthralgia (non-gouty — common)
GI disturbance
Rash and photosensitivity
Sideroblastic anaemia (rare)

Interactions

Other hepatotoxic drugs — additive (rifampicin, isoniazid — monitor LFTs closely)
Uricosuric drugs — antagonised by pyrazinamide
Allopurinol — reduced efficacy (pyrazinamide blocks renal urate excretion)

Monitoring

LFTs at baseline, 2 and 4 weeks, then monthly
Uric acid (baseline and monthly)
Gout symptoms
Visual acuity (combination with ethambutol)

Reference: BNFc; BNF 90; NICE NG33 (TB); WHO TB Treatment Guidelines 2022; PHE Tuberculosis Treatment Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways