Drug reference

Pyrazinamide

First-line antitubercular agent (synthetic pyrazine analog of nicotinamide) · Antimycobacterial

Also known as PZA

START

Baseline LFTs, uric acid. Verify not acute gout. Counsel on hepatotoxicity symptoms (jaundice, dark urine, fatigue). ALWAYS used in combination (never monotherapy).

TYPICAL MAX

2g/day. Intensive phase only (first 2 months). Discontinue after intensive phase—continuation phase uses only rifampicin + isoniazid.

STOP IF

ALT/AST >3x ULN with symptoms or >5x ULN asymptomatic, severe arthralgia with gout, severe rash, SJS/TEN.

WATCH

LFTs monthly (more frequent with hepatic risk factors). Uric acid—arthralgia is common but usually not gout; treat symptomatically if needed. Photosensitivity—sun protection. Hepatotoxicity risk additive with rifampicin and isoniazid—all three together carry highest risk.

CDSCO approvedSchedule HJan AushadhiNPPA price-controlledATC J04AK01

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 30min · Onset ~30 min
PEAK: 1.5h · Tmax 1-2 hours
t½: 9.5h · t½ ~9-10 hours
DURATION: 1d · 24 hours (QD)

EXCRETION

Renal as metabolites (~70%)

route + CYP

INTERACTIONS

6 major

SEVERE in our sources

PREGNANCY

Safe in pregnancy—no teratogenic effects. Hyperuricemia risk may be higher; monitor uric acid. Essential component of standard TB regimens in pregnancy.

FDA category + note

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Available in India

75 branded formulations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Converted by mycobacterial pyrazinamidase to pyrazinoic acid, which accumulates in acidic environments (macrophage phagolysosomes, caseous granulomas) and disrupts membrane transport and energy production. Uniquely effective against semi-dormant bacilli in acidic environments—sterilizing activity.

Indications

Tuberculosis (active disease—first-line, intensive phase only)Latent tuberculosis infection (short-course regimens—in combination)

Dosing

Adult: Active TB: 20-25mg/kg PO daily (max 2g) or 50-75mg/kg 2-3x/week (DOT, max 3-4g). Intensive phase only (first 2 months of therapy). Take with rifampicin and isoniazid.
Pediatric: 30-40mg/kg/day PO (max 2g) or 50mg/kg 2x/week. Intensive phase only.
Renal adjustment: CrCl <30: 25-35mg/kg 3x/week (not daily); avoid accumulation.
Hepatic adjustment: Avoid in severe hepatic impairment; use with caution in chronic liver disease.
Geriatric: Use 15-20mg/kg; increased hepatotoxicity and hyperuricemia risk.
Max dose: 2g/day (daily); 3-4g/dose (intermittent)

Pharmacokinetics

Onset

Sterilizing effect on dormant bacilli; clinical improvement 2-4 weeks

Peak effect

Tmax 1-2 hours; penetrates well into CSF (100% in inflamed meninges)

Duration

24 hours (QD dosing)

Half-life

~9-10 hours (variable; 2-10h in children; longer in renal impairment)

Bioavailability

~90%

Protein binding

~10%

Metabolism

Hepatic hydrolysis by pyrazinamidase to pyrazinoic acid (active), then oxidation to 5-hydroxypyrazinoic acid (inactive)

Excretion

~70% renal (metabolites); ~4% unchanged in urine

Contraindications

Acute hepatic disease or severe hepatic impairment
Acute gout (pyrazinamide raises uric acid)
Hypersensitivity to pyrazinamide
Porphyria

Side effects

Common

Hepatotoxicity (dose-dependent; usually reversible)Hyperuricemia / arthralgia (gout risk)Nausea and vomitingAnorexiaRashFever

Serious

Severe hepatotoxicity (can be fatal—risk increased with rifampicin co-therapy)
Severe gout / acute uric acid nephropathy
Thrombocytopenia
Sideroblastic anemia
Photosensitivity
SJS/TEN (rare)

Pregnancy & lactation

Pregnancy

Safe in pregnancy—no teratogenic effects. Hyperuricemia risk may be higher; monitor uric acid. Essential component of standard TB regimens in pregnancy.

Lactation

Compatible with breastfeeding; excreted in milk but infant receives subtherapeutic amounts. Continue breastfeeding.