Comprehensive Guide to Isoniazid: Uses, Dosage, Side Effects, and More
What is Isoniazid?
Overview of Isoniazid
Generic Name: Isoniazid
Brand Name: Nydrazid, generics
Drug Group: Antitubercular (antibacterial)
Commonly Used For
- Treat active tuberculosis (TB).
- Prevent latent TB infection (LTBI) progression.
- Manage TB meningitis.
Key Characteristics
Form: Oral tablets (100 mg, 300 mg), syrup (50 mg/5 mL), or injectable solution (100 mg/mL) (detailed in Dosage section).
Mechanism: Inhibits InhA enzyme, disrupting mycolic acid production in TB bacteria.
Approval: FDA-approved (1952) and EMA-approved for TB treatment and prophylaxis.
Indications and Uses of Isoniazid
Isoniazid is indicated for a range of mycobacterial infections and preventive therapies, leveraging its bactericidal and bacteriostatic properties:
Active Tuberculosis (TB): Treats pulmonary and extrapulmonary TB caused by Mycobacterium tuberculosis, per infectious disease guidelines, supported by clinical trials showing 90–95% efficacy in combination therapy.
Latent TB Infection (LTBI) Prophylaxis: Prevents progression to active TB in high-risk individuals (e.g., HIV-positive, recent converters), recommended in public health protocols with evidence of 60–80% prevention rates.
TB Meningitis: Manages central nervous system TB, reducing mortality, with neurology-infectious disease data.
TB Lymphadenitis: Investigated off-label to treat scrofula, improving lymph node resolution, per surgical pathology studies.
Disseminated TB (Miliary TB): Used off-label in severe systemic cases, with critical care evidence.
TB Pericarditis: Managed off-label to reduce pericardial effusion, with cardiology-infectious disease research.
Pediatric TB: Initiated off-label in children with multidrug-resistant strains, with pediatric pulmonology data.
Non-Tuberculous Mycobacteria (NTM): Explored off-label for Mycobacterium avium complex (MAC) in immunocompromised patients, with infectious disease studies.
Preventive Therapy in Contacts: Applied off-label in household contacts of multidrug-resistant TB cases, with epidemiology evidence.
TB in Pregnancy: Used off-label with monitoring, with obstetrics-infectious disease research.
Dosage of Isoniazid
Dosage for Adults
Active TB: 5 mg/kg once daily (max 300 mg/day) or 15 mg/kg 2–3 times weekly (max 900 mg), in combination with rifampin and ethambutol, for 6–9 months.
Latent TB Infection (LTBI): 300 mg once daily or 900 mg twice weekly for 6–9 months, often with pyridoxine (vitamin B6) to prevent neuropathy.
TB Meningitis: 10–15 mg/kg daily (max 300 mg), with higher initial doses (up to 20 mg/kg) under specialist care, for 9–12 months.
Dosage for Children
Active TB: 10–15 mg/kg once daily (max 300 mg/day) or 20–30 mg/kg 2–3 times weekly (max 900 mg), under pediatric infectious disease supervision.
LTBI: 10–15 mg/kg once daily (max 300 mg/day) for 9 months, with pyridoxine supplementation.
Dosage for Pregnant Women
Pregnancy Category C: Use only if benefits outweigh risks; consult an obstetrician and infectious disease specialist, with fetal monitoring and pyridoxine.
Dosage Adjustments
Renal Impairment:
Mild to moderate (CrCl 10–50 mL/min): No adjustment; severe (CrCl <10 mL/min): Reduce to 200 mg/day or avoid.
Hepatic Impairment:
Mild (Child-Pugh A): Use cautiously; moderate to severe (Child-Pugh B or C): Avoid or adjust with liver function tests.
Concomitant Medications: Adjust if combined with rifampin or phenytoin, increasing hepatotoxicity or drug levels; monitor.
Elderly: Start with 5 mg/kg/day; monitor for neuropathy and liver function.
Malnutrition: Increase pyridoxine dose (25–50 mg/day) to prevent neuropathy in at-risk patients.
Additional Considerations
- Administer this active ingredient orally on an empty stomach (1 hour before or 2 hours after meals) to enhance absorption.
- Use with pyridoxine (10–25 mg/day) in high-risk groups (e.g., alcoholics, diabetics) to prevent peripheral neuropathy.
How to Use Isoniazid
Administration:
Oral: Swallow tablets whole with water, or use syrup with a calibrated device; inject IV/IM only under medical supervision.
Take consistently at the same time daily to maintain therapeutic levels.
Timing: Administer 1 hour before or 2 hours after meals; avoid antacids or food interference.
Monitoring: Watch for jaundice, numbness, or signs of hepatotoxicity (e.g., dark urine); report changes immediately.
Additional Tips:
- Store at 20–25°C (68–77°F), protecting from light and moisture.
- Keep out of reach of children due to hepatotoxicity risk.
- Educate patients on alcohol avoidance to reduce liver strain; provide a medication diary.
- Schedule liver function tests (ALT, AST) monthly during the first 3 months of therapy.
- Use with a DOT (Directly Observed Therapy) program if recommended to ensure adherence.
Contraindications for Isoniazid
Hypersensitivity: Patients with a known allergy to Isoniazid or its derivatives.
Acute Liver Disease: Contraindicated in active hepatitis or cirrhosis due to hepatotoxicity risk.
Previous Isoniazid-Associated Liver Injury: Avoid in patients with a history of severe Isoniazid-induced hepatitis.
Severe Renal Impairment: Contraindicated in CrCl <10 mL/min without dose adjustment.
Alcoholism: Avoid in active alcohol abuse due to increased hepatotoxicity.
Porphyria: Contraindicated due to potential exacerbation of porphyric crises.
Warnings & Precautions for Isoniazid
General Warnings
Hepatotoxicity: Risk of severe liver injury or hepatitis; monitor ALT/AST monthly, especially in the first 3 months.
Peripheral Neuropathy: Risk in malnourished or diabetic patients; supplement with pyridoxine.
Seizures: Rare risk, especially with high doses or drug interactions; monitor neurological status.
Psychosis: Risk of mood changes or hallucinations; assess mental health.
Hypersensitivity Reactions: Rare severe reactions (e.g., rash, fever); discontinue if present.
Additional Warnings
Optic Neuritis: Risk with prolonged use; perform eye exams every 6 months.
Hyperglycemia: Risk in diabetic patients; monitor glucose levels.
Vitamin B6 Deficiency: Increased neuropathy risk; ensure pyridoxine supplementation.
Drug Resistance: Risk with monotherapy; always use in combination regimens.
Lupus-Like Syndrome: Rare autoimmune reaction; monitor for joint pain or rash.
Use in Specific Populations
Pregnancy: Category C; use with caution, monitoring fetal liver function.
Breastfeeding: Use caution; monitor infant for hepatotoxicity signs.
Elderly: Higher risk of neuropathy and liver damage; start with lower doses.
Children: Safe with pediatric oversight and pyridoxine.
Renal/Hepatic Impairment: Adjust or avoid based on severity.
Additional Precautions
- Inform your doctor about liver disease, diabetes, or alcohol use before starting this medication.
- Avoid tyramine-rich foods (e.g., aged cheese) to prevent hypertensive crisis if combined with certain drugs.
- Use regular monitoring to detect early signs of adverse effects.
Overdose and Management of Isoniazid
Overdose Symptoms
- Nausea, vomiting, or dizziness.
- Severe cases: Seizures, metabolic acidosis, or coma due to pyridoxine depletion.
- Hyperreflexia, slurred speech, or tachycardia as early signs.
- Hepatic failure or respiratory depression with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help if overdose is suspected.
Supportive Care: Administer IV fluids, correct acidosis with sodium bicarbonate, and manage seizures with benzodiazepines.
Specific Treatment: Use pyridoxine (vitamin B6) at a 1:1 gram ratio to the Isoniazid dose (e.g., 5 g for 5 g overdose) to reverse toxicity.
Monitor: Check liver function, acid-base status, and neurological signs for 24–48 hours.
Patient Education: Advise against hoarding medication and to report accidental ingestion immediately.
Additional Notes
- Overdose risk is high with intentional misuse; store securely and limit access.
- Report persistent symptoms (e.g., seizures, yellowing skin) promptly to prevent long-term damage.
Side Effects of Isoniazid
Common Side Effects
- Nausea (10–20%, managed with food timing)
- Peripheral Neuropathy (5–15%, prevented with pyridoxine)
- Fatigue (5–10%, decreases with rest)
- Rash (3–8%, relieved with antihistamines)
- Hepatic Enzyme Elevation (2–6%, monitored with tests)
These effects may subside with adaptation or dose adjustment.
Serious Side Effects
Seek immediate medical attention for:
- Hepatic: Jaundice, hepatitis, or liver failure (ALT/AST >3x upper limit).
- Neurological: Seizures or severe neuropathy.
- Psychiatric: Psychosis or depression.
- Metabolic: Severe acidosis or hyperglycemia.
- Allergic: Anaphylaxis or Stevens-Johnson syndrome (rare).
Additional Notes
Regular monitoring with liver function tests (ALT, AST) every 1–2 weeks during the first 2 months is essential to detect hepatotoxicity early.
Patients with a history of neuropathy should receive higher pyridoxine doses (50 mg/day) and monthly nerve conduction studies if symptoms persist.
Report any unusual symptoms (e.g., dark urine, numbness in extremities) immediately to a healthcare provider to address potential toxicity.
Long-term use (>6 months) requires ophthalmologic exams to monitor for optic neuritis and baseline mental health assessments.
Drug Interactions with Isoniazid
This active ingredient may interact with:
- Rifampin: Increases hepatotoxicity; monitor liver function.
- Phenytoin: Raises phenytoin levels; adjust dose and monitor.
- Alcohol: Potentiates liver damage; avoid combination.
- Disulfiram: Causes psychotic reactions; avoid use.
- Theophylline: Increases theophylline levels; monitor and adjust.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Use this antitubercular as prescribed for TB, following the daily or weekly schedule.
Monitoring: Report jaundice, numbness, or mood changes immediately.
Lifestyle: Avoid alcohol; maintain a balanced diet rich in B6 (e.g., bananas, potatoes).
Diet: Take on an empty stomach; avoid tyramine-rich foods if on interacting drugs.
Emergency Awareness: Know signs of liver failure or seizures; seek care if present.
Follow-Up: Schedule regular check-ups every 1–2 weeks to monitor liver function and neuropathy.
Pharmacokinetics of Isoniazid
Absorption: Oral, peak at 1–2 hours; bioavailability ~90–100%.
Distribution: Volume of distribution ~0.6 L/kg; 10–15% protein-bound.
Metabolism: Hepatic via N-acetyltransferase (fast/slow acetylators); half-life varies (1–4 hours).
Excretion: Primarily renal (75–95% as metabolites); half-life 1–4 hours.
Half-Life: 1–4 hours, prolonged in slow acetylators or renal impairment.
Pharmacodynamics of Isoniazid
This drug exerts its effects by:
Inhibiting InhA enzyme, disrupting mycolic acid synthesis in Mycobacterium tuberculosis.
Exerting bactericidal action against actively dividing TB bacilli.
Exhibiting dose-dependent risks of hepatotoxicity and neuropathy.
Storage of Isoniazid
- Temperature: Store at 20–25°C (68–77°F); protect from light and moisture.
- Protection: Keep in original container, away from heat and humidity.
- Safety: Store in a secure location out of reach of children and pets due to hepatotoxicity risk.
- Disposal: Dispose of unused tablets or solution per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Isoniazid treat?
A: This medication treats and prevents tuberculosis.
Q: Can this active ingredient cause nausea?
A: Yes, nausea is common; take on an empty stomach.
Q: Is Isoniazid safe for children?
A: Yes, with supervision and pyridoxine.
Q: How is this drug taken?
A: Orally or via injection, as directed.
Q: How long is Isoniazid treatment?
A: 6–9 months for active TB, or 9 months for LTBI.
Q: Can I use Isoniazid 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 1952 for TB treatment and prophylaxis.
European Medicines Agency (EMA): Approved for active and latent TB.
Other Agencies: Approved globally for tuberculosis; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Nydrazid (Isoniazid) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Isoniazid Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Isoniazid: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Isoniazid.
- WHO’s inclusion of Isoniazid for tuberculosis.
- American Journal of Respiratory and Critical Care Medicine. (2022). Isoniazid in Latent TB.
- Peer-reviewed article on Isoniazid efficacy (note: access may require a subscription).
