What to do if an adverse drug reaction (ADR) occurs with isoniazid (antitubercular drug)?

Management of Adverse Drug Reactions with Isoniazid

In case of an adverse drug reaction to isoniazid, immediately discontinue the drug and provide appropriate supportive care based on the specific reaction type. 1

Types of Adverse Reactions and Management

Hepatotoxicity

• Immediate action: Stop isoniazid if AST/ALT levels exceed 3x upper limit of normal with symptoms or 5x upper limit without symptoms 1, 2
• Monitor liver function tests monthly for patients:
  • Age >35 years
  • Daily alcohol users
  • Chronic liver disease
  • HIV infection
  • Postpartum women (especially Black and Hispanic)
  • On medications with known interactions 2
• Investigate non-drug etiologies (viral hepatitis, etc.) 1
• Continue treatment with less hepatotoxic drugs if needed (ethambutol, fluoroquinolones) 1

Hypersensitivity Reactions/Rash

• Mild reactions: Provide symptomatic relief with antihistamines 1, 3
• Stevens-Johnson syndrome/severe reactions: Immediately stop all medications until symptoms resolve 1, 3
• Sequential reintroduction after resolution:
  • Restart TB medications one by one every 2 days
  • Monitor response closely 1
  • Start with small doses (isoniazid 50 mg/day) and gradually increase to target dose 3

Peripheral Neuropathy

• Preventive measure: Administer pyridoxine 10 mg daily for high-risk patients (diabetics, alcoholics, HIV-positive, chronic renal failure, malnourished) 1
• Management:
  • Mild reactions: Increase pyridoxine dose or reduce isoniazid dose 1
  • Severe/persistent: Stop isoniazid 1

Neuropsychiatric Effects

• Verify correct dosing 1
• Reduce dosage of suspected drug and monitor effect 1
• If no improvement, stop the drug 1

Isoniazid Overdose

• Recognize symptoms: seizures, metabolic acidosis, coma (appearing 30 minutes to 2 hours after ingestion) 4
• Administer pyridoxine in gram-per-gram amounts of isoniazid ingested 4

Reporting Requirements

• Any adverse effect leading to hospital admission or death must be reported to:
  • Local or state health departments for inclusion in the National Surveillance for Severe Adverse Events 1
  • FDA's MedWatch program (1-800-FDA-1088) 1

Reintroduction Protocol

If isoniazid must be reintroduced after an adverse reaction:

1. Wait until symptoms and laboratory abnormalities have completely cleared 2
2. Start with very small doses and gradually increase 2
3. Withdraw immediately if any indication of recurrent reaction 2

High-Risk Groups Requiring Closer Monitoring

• Age >35 years (risk increases with age) 2
• Daily alcohol users 2
• Patients with chronic liver disease 2
• HIV-positive individuals 2
• Women, particularly Black and Hispanic women 2
• Postpartum women 2
• Patients on multiple medications 2, 5

Common Pitfalls to Avoid

• Failure to recognize early signs of hepatotoxicity (anorexia, nausea, vomiting, dark urine, jaundice) 2
• Continuing isoniazid despite symptoms of liver damage, which can lead to more severe liver injury 2
• Not monitoring liver function tests in high-risk patients 2
• Overlooking drug interactions (especially with acetaminophen, carbamazepine, phenytoin, and theophylline) 2
• Administering isoniazid with food, which reduces bioavailability 2

Remember that early recognition and prompt management of adverse drug reactions are crucial to prevent serious complications and ensure successful tuberculosis treatment.