Clinical beta

FMBM is currently in clinical beta. Content is for professional review/testing and must not replace local protocols, senior clinical judgment, or official prescribing references.

Drug Monograph

Pyrazinamide

Pyrazinamide

Antitubercular (PO)

TBHepatotoxicityHyperuricemia

Indication

Active TB intensive phase

At a glance

INDICATIONS (CORE USE)

**Intensive phase TB** only first 2 months typically β€” **hepatotoxicity**; **hyperuricemia/gout**; **hepatic dosing** in liver disease.

ADULT DOSE (STANDARD)

25 mg/kg PO daily max 2 g; intermittent 50–70 mg/kg 2Γ—/week max 4 g

MAX DOSE

2 g/day daily therapy adult typical max

Route

PO

PEDIATRIC DOSE

35 mg/kg/day max 2 g daily phase

Do not miss

Must-not-miss safety points

Major warning

- **Hepatitis** additive with INH/rifampin β€” LFTs - **Hyperuricemia** β†’ gout flare β€” symptom check - Not used latent standard regimens

Indications

USE IF: Active TB intensive phase per regimen. AVOID IF: Severe gout uncontrolled; acute hepatitis; pregnancy relative first trimester nuance β€” TB program decides.

Primary

  • Active pulmonary/extrapulmonary tuberculosis intensive-phase combination

Other

  • Never monotherapy

Dosing

STANDARD (ADULT PO)

~25 mg/kg/day PO (max ~2 g/day) daily Γ— 2 mo intensive phase (RIPE)

ADULT DOSE

Weight-based daily 2 months standard RIPE

PEDIATRIC DOSE

mg/kg per pediatric TB center.

MAX DOSE

2 g/day daily max typical

Practical Note

Stop after intensive phase unless special meningitis regimens extend β€” program-specific.

Warnings

Clinical warnings

  • Arthralgias
  • Photosensitivity rare

Adverse effects

  • hepatotoxicity
  • hyperuricemia
  • GI upset

Contraindications

  • Acute gout flare initiation relative
  • Severe liver disease

Drug interactions

  • Zidovudine myelosuppression stack
  • Probenecid β€” uric acid handling

Special populations

Pediatrics

35 mg/kg/day max 2 g daily phase

Pregnancy

Generally used in TB pregnancy regimens β€” program

Lactation

compatible.

Renal impairment

Gout risk still; uric acid monitoring if symptomatic. **CrCl scaffold (FMBM β€” titrate to FDA/SFDA label + institutional pharmacy nomogram):** - **CrCl β‰₯50** β†’ standard RIPE dosing per program - **CrCl 10–50** β†’ hepatic elimination emphasis β€” urate monitoring if arthralgia - **CrCl <10** β†’ severe renal failure β€” per TB program (urate/hepatic surveillance)

Hepatic impairment

Reduce/hold if hepatitis develops β€” restart per hepatology/TB program.

Elderly

Hepatic + hyperuricemia.

Administration

PO daily DOT.

Monitoring

  • Monitor: - RIPE regimen β†’ **LFTs**; arthralgia β†’ **uric acid** - Intensive phase duration β†’ program-defined β€” do not extend without indication - LFTs with other hepatotoxic TB drugs - Joint pain β†’ uric acid - Clinical TB improvement 2 months β†’ continuation phase switch
  • Recheck: - No clinical improvement at 48–72h β†’ reassess diagnosis, resistance, source control, and drug interactions - If targets not met after reassessment of dose, organ function, and interactions β†’ escalate per protocol (DO NOT continue blindly)

Overdose / toxicity

Clinical Picture

**Life-threatening (first):** **fulminant hepatitis**. **Secondary:** hyperuricemia/gout flare.

Immediate Actions

Stop β†’ LFTs; uric acid if arthralgia

Antidote

No specific antidote; treat complications (e.g. anaphylaxis β†’ epinephrine per ACLS)

Decontamination

Supportive

Escalation

Fulminant hepatic failure β†’ **ICU** / hepatology

Clinical pearls

Common mistakes, resistance logic, and bedside traps

High-Yield Summary

**First 2 months** of TB RIPE β€” not latent therapy. **Uric acid** climbs β€” gout patients suffer. **Triple hepatitis** with INH/RIF β€” LFTs.

Clinical pearls

Intensive vs continuation phase is a protocol β€” don’t improvise duration. Steroids for TB pericarditis/meningitis β€” separate issue. *Stewardship (all antimicrobials):* Empiric choice β†’ syndrome severity + **local antibiogram**; shortest effective course.

Stewardship & safety

  • 2-month phase
  • Uric acid
  • LFTs with RIF/INH

Pharmacokinetics

Hepatic metabolism; penetrates macrophages well.

Mechanism of action

Pyrazinoic acid in acidic macrophage environment disrupts mycobacterial membrane/energy.

Common brand names

Global data (no country-specific data available)

Saudi Arabia

(placeholder β€” verify local formulary)

Common trade names are curated examples only β€” formulations and availability vary. Verify the exact product name with your local pharmacy and national regulator before prescribing or dispensing.

Country practice notes

  • Empiric choice β†’ tie to syndrome, severity, and local antibiogram β€” not habit.
  • IV β†’ PO step-down when oral bioavailability and susceptibility allow.
  • Do not use antibiotics for uncomplicated viral illness β€” stewardship.

References

Saudi Arabia

  • SFDA (Saudi Food & Drug Authority)
  • Saudi National Formulary / MOH (where available)

International

  • WHO Model List of Essential Medicines (verify current edition)
  • US FDA or EU EMA product information (when national SmPC is unavailable)
  • Sanford Guide
  • IDSA / ESCMID (indication-specific)
  • Local antimicrobial stewardship / hospital formulary
  • FDA / SFDA / regional product labeling
  • Sanford Guide
  • IDSA / ESCMID (indication-specific)
  • Local antimicrobial stewardship / hospital formulary
  • FDA / SFDA / regional product labeling

Do not miss

  • Uncomplicated viral URI/bronchitis β†’ antibiotics rarely indicated
  • Narrow or stop when susceptibilities + clinical stability allow
  • Continuing pyrazinamide beyond intensive phase by mistake β†’ unnecessary toxicity.
  • Arthritis mistaken for TB worsening.
  • 2-month phase
  • Uric acid
  • LFTs with RIF/INH