Comprehensive Guide to Pyrazinamide: Uses, Dosage, Side Effects, and More
What is Pyrazinamide?
Overview of Pyrazinamide
Generic Name: Pyrazinamide
Brand Name: Various generics (no prominent brand)
Drug Group: Antitubercular (antimycobacterial)
Commonly Used For
- Treat active tuberculosis (TB).
- Manage latent TB infection.
- Prevent TB progression in high-risk individuals.
Key Characteristics
Form: Oral tablets (500 mg) or suspension (detailed in Dosage section).
Mechanism: Disrupts mycolic acid synthesis in M. tuberculosis, effective in acidic phagolysosomes.
Approval: FDA-approved (1970s) and EMA-approved for TB treatment.
Indications and Uses of Pyrazinamide
Pyrazinamide is indicated for tuberculosis management, leveraging its bactericidal and sterilizing effects:
Active Tuberculosis (TB): Treats pulmonary and extrapulmonary TB in adults and children, used in the initial intensive phase with isoniazid and rifampin, per WHO and CDC guidelines, shortening treatment duration to 6 months.
Latent TB Infection (LTBI): Manages LTBI in high-risk individuals (e.g., HIV co-infection, recent exposure), preventing progression to active disease, supported by public health campaigns.
Multidrug-Resistant TB (MDR-TB): Employed as a second-line agent in MDR-TB regimens, enhancing efficacy when combined with fluoroquinolones and injectable drugs, per global TB control programs.
TB Meningitis: Used off-label in TB meningitis to penetrate the central nervous system, reducing inflammation and bacterial load, with evidence from neurology and infectious disease studies.
TB in HIV Co-Infection: Treats TB in HIV patients, adjusting for drug interactions (e.g., with antiretrovirals), improving survival rates, supported by HIV/TB co-infection research.
Pediatric TB: Manages TB in children (2+ years), with weight-based dosing, enhancing adherence and cure rates, per pediatric infectious disease protocols.
Extrapulmonary TB (e.g., Lymph Node TB): Addresses extrapulmonary forms like lymphadenitis, reducing lesion size, with data from surgical and infectious disease cohorts.
TB Pericarditis: Investigated off-label for TB pericarditis, reducing effusion and improving cardiac function, with cardiology and TB research support.
Disseminated TB: Used off-label in disseminated (miliary) TB, controlling systemic infection, with emerging evidence from critical care and TB studies.
Dosage of Pyrazinamide
Dosage for Adults
Active TB (Initial Phase): 15–30 mg/kg once daily (maximum 2 g/day) or 50 mg/kg twice or thrice weekly, taken with food, with isoniazid and rifampin.
Latent TB Infection (LTBI): 15–20 mg/kg once daily (maximum 2 g/day) for 2–3 months, often with isoniazid.
Dosage for Children
Active TB (2+ years, weight-based): 15–30 mg/kg once daily (maximum 2 g/day) or 50 mg/kg twice weekly, under pediatric infectious disease supervision.
Not recommended under 2 years unless critical.
Dosage for Pregnant Women
Pregnancy Category C: Limited data; use only if benefits outweigh risks (e.g., active TB). Consult an obstetrician, with fetal monitoring.
Dosage Adjustments
Renal Impairment: Reduce dose to 12–20 mg/kg if CrCl <30 mL/min; avoid in dialysis patients unless adjusted.
Hepatic Impairment: Mild (Child-Pugh A): No adjustment; moderate (Child-Pugh B): Use caution; severe (Child-Pugh C): Avoid.
Elderly: Start with 15 mg/kg once daily; increase cautiously to 25 mg/kg if tolerated.
Concomitant Medications: Adjust if combined with hepatotoxic drugs (e.g., acetaminophen), monitoring liver function.
Additional Considerations
- Take this active ingredient with food to reduce gastrointestinal irritation.
- Use a pill organizer for consistent daily or intermittent dosing.
How to Use Pyrazinamide
Administration:
Swallow tablets or administer suspension with a meal or snack, using water; shake suspension well.
Take as part of a multi-drug TB regimen, maintaining the same schedule.
Timing: Use once daily or as prescribed (e.g., thrice weekly in directly observed therapy), ensuring consistency.
Monitoring: Watch for jaundice, joint pain, or signs of liver issues (e.g., dark urine).
Additional Tips:
- Store at 20–25°C (68–77°F), protecting from moisture and heat.
- Keep out of reach of children due to toxicity risk.
- Report severe fatigue, abdominal pain, or signs of gout immediately.
Contraindications for Pyrazinamide
Hypersensitivity: Patients with a known allergy to Pyrazinamide or related nicotinamides.
Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C due to hepatotoxicity risk.
Acute Gout: Avoid due to hyperuricemia exacerbation.
Severe Renal Impairment: Contraindicated if CrCl <30 mL/min without dose adjustment.
Side Effects of Pyrazinamide
Common Side Effects
- Hyperuricemia (20–40%, monitor for gout)
- Hepatotoxicity (10–20%, reversible with monitoring)
- Nausea (5–15%, manageable with food)
- Anorexia (5–10%, improved with nutrition)
- Arthralgia (5–10%, relieved with rest)
These effects may subside with dose adjustment.
Serious Side Effects
Seek immediate medical attention for:
- Hepatic: Jaundice, hepatitis, or liver failure.
- Metabolic: Severe hyperuricemia or gout attacks.
- Gastrointestinal: Severe nausea, vomiting, or pancreatitis.
- Hematologic: Thrombocytopenia or sideroblastic anemia.
- Allergic: Rash, angioedema, or anaphylaxis.
Additional Notes
- Regular monitoring for liver function, uric acid, and blood counts is advised.
- Report any unusual symptoms (e.g., yellow skin, severe joint swelling) immediately to a healthcare provider.
Warnings & Precautions for Pyrazinamide
General Warnings
Hepatotoxicity: Risk of liver injury or hepatitis; monitor liver enzymes monthly.
Hyperuricemia: Increases uric acid levels, risking gout; monitor joint pain.
Photosensitivity: Skin reactions to sunlight; use protection.
Gastrointestinal Distress: Nausea or anorexia; use with food.
Porphyria: Risk of exacerbation; avoid in diagnosed cases.
Additional Warnings
Neurological Effects: Rare peripheral neuropathy; report numbness or tingling.
Blood Disorders: Rare thrombocytopenia or sideroblastic anemia; monitor blood counts.
Diabetes Mellitus: May worsen glucose control; monitor blood sugar.
Renal Impairment: Monitor in severe cases; adjust if necessary.
Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.
Use in Specific Populations
- Pregnancy: Category C; use only if essential with fetal monitoring.
- Breastfeeding: Excreted in breast milk; monitor infant for effects.
- Elderly: Higher risk of toxicity; start with lower doses.
- Children: Limited to 2+ years; supervise closely.
- Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.
Additional Precautions
- Inform your doctor about liver disease, gout, or medication history before starting this medication.
- Avoid alcohol to reduce hepatotoxicity risk.
Overdose and Management of Pyrazinamide
Overdose Symptoms
- Nausea, vomiting, or severe hyperuricemia.
- Severe cases: Liver failure, gout flare, or metabolic acidosis.
- Fatigue, joint pain, or jaundice as early signs.
- Seizures with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer IV fluids, monitor vital signs, and correct electrolytes.
Specific Treatment: Manage liver function and uric acid levels; no specific antidote.
Monitor: Check liver enzymes, kidney function, and uric acid for 24–72 hours.
Additional Notes
- Overdose risk is moderate; store securely.
- Report persistent symptoms (e.g., severe joint pain, yellowing skin) promptly.
Drug Interactions with Pyrazinamide
This active ingredient may interact with:
- Hepatotoxic Drugs: Enhances liver damage (e.g., isoniazid, rifampin); monitor.
- Allopurinol: Alters uric acid levels; adjust dose.
- Antacids: Reduces absorption; separate administration by 2 hours.
- Oral Contraceptives: Potential reduced efficacy; use backup methods.
- Probenecid: Increases hyperuricemia risk; avoid combination.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Take this antitubercular as prescribed to manage TB, following the exact schedule, often under directly observed therapy (DOT).
Monitoring: Report jaundice, joint pain, or fatigue immediately.
Lifestyle: Avoid alcohol; maintain hydration and a balanced diet.
Diet: Take with food to reduce stomach upset; avoid purine-rich foods to manage uric acid.
Emergency Awareness: Know signs of liver failure or gout flare; seek care if present.
Follow-Up: Schedule regular check-ups every 1–2 months to monitor liver function, uric acid, and TB progression.
Pharmacokinetics of Pyrazinamide
Absorption: Well-absorbed orally (peak at 1–2 hours); enhanced with food.
Distribution: Volume of distribution ~0.6 L/kg; penetrates CSF and tissues.
Metabolism: Hepatic via xanthine oxidase to 5-hydroxypyrazinoic acid, active metabolite.
Excretion: Primarily renal (70%) as metabolites; half-life 9–10 hours.
Half-Life: 9–10 hours, with prolonged effect in acidic environments.
Pharmacodynamics of Pyrazinamide
This drug exerts its effects by:
- Inhibiting mycolic acid synthesis in M. tuberculosis, particularly in acidic phagolysosomes.
- Exerting sterilizing activity against semi-dormant bacilli, shortening treatment duration.
- Demonstrating dose-dependent hepatotoxicity and hyperuricemia risks.
- Enhancing efficacy when combined with rifampin and isoniazid.
Storage of Pyrazinamide
Temperature: Store at 20–25°C (68–77°F); protect from moisture.
Protection: Keep in original container, away from light.
Safety: Store in a locked container out of reach of children due to toxicity risk.
Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Pyrazinamide treat?
A: This medication treats active and latent tuberculosis.
Q: Can this active ingredient cause joint pain?
A: Yes, joint pain may occur due to hyperuricemia; report if severe.
Q: Is Pyrazinamide safe for children?
A: Yes, for 2+ years with a doctor’s guidance.
Q: How is this drug taken?
A: Orally as tablets with food, as directed.
Q: How long is Pyrazinamide treatment?
A: Typically 2–6 months for TB, depending on regimen.
Q: Can I use Pyrazinamide if pregnant?
A: Yes, with caution; consult a doctor.
Regulatory Information
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in the 1970s for TB treatment.
European Medicines Agency (EMA): Approved for tuberculosis management.
Other Agencies: Approved globally for TB; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Pyrazinamide Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Pyrazinamide Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Pyrazinamide: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Guidelines on Tuberculosis Treatment: Pyrazinamide.
- WHO’s recommendations for Pyrazinamide in TB therapy.
- The Lancet Infectious Diseases. (2022). Pyrazinamide in MDR-TB Management.
- Peer-reviewed article on Pyrazinamide efficacy (note: access may require a subscription).
