What are the side effects of isoniazid (Isonicotinic Hydrazide)?

Isoniazid Side Effects

Isoniazid can cause several significant side effects, with hepatotoxicity being the most severe and peripheral neuropathy being the most common, requiring careful monitoring and preventive measures during treatment.

Major Side Effects

Hepatotoxicity

• Hepatitis is the most severe toxic effect of isoniazid 1
• Risk factors include:
  • Increasing age (highest risk in persons >50 years old) 1
  • Daily alcohol consumption (fourfold higher risk) 1
  • Pregnancy, especially in third trimester and immediate postpartum period 1
• Clinical manifestations include:
  • Elevated liver enzymes 1
  • Hepatitis 1
  • Potentially fatal liver injury if not detected early 1
• Monitoring recommendations:
  • Monthly clinical monitoring for symptoms of hepatotoxicity 1
  • Baseline liver function tests in selected cases (older patients, those with risk factors) 1
  • Patients should stop medication immediately if symptoms of hepatotoxicity occur 1

Neurological Effects

• Peripheral neuropathy is a common side effect 1
• Manifestations include:
  • Numbness and paresthesia in extremities 1, 2
  • Progressive loss of distal sensation 1, 2
  • Motor ataxia and weakness 1, 2
  • Loss of deep tendon reflexes 1, 2
• Other neurological effects:
  • Seizures (rare, but can occur especially in patients with renal failure) 3
  • Mild central nervous system effects 1
  • Psychosis (rare) 1

Other Side Effects

• Hematological:
  • Agranulocytosis 1
  • Megaloblastic anemia 1
  • Thrombocytopenia 1
• Immunological:
  • Rash 1
  • Drug-induced lupus (rare) 1
• Musculoskeletal:
  • Arthralgia 1
  • Rhabdomyolysis 1
• Drug interactions:
  • Increased levels of phenytoin (Dilantin) 1
  • Increased levels of disulfiram (Antabuse) 1

Prevention and Management

Peripheral Neuropathy Prevention

• Pyridoxine (vitamin B6) supplementation:
  • Recommended dose: 10-25 mg/day for prevention 1, 2
  • Higher doses (50-100 mg daily) for treatment of established neuropathy 2
  • Especially important for high-risk patients: diabetes, uremia, alcoholism, malnutrition, HIV infection 2, 4
• Avoid excessive pyridoxine doses (>200 mg daily) as this can itself cause peripheral neuropathy 2

Hepatotoxicity Management

• Monthly clinical monitoring is recommended 1
• Patient education about symptoms of hepatotoxicity 1
• Instructions to stop medication immediately if symptoms occur 1
• Consider dose adjustment in slow acetylators 4

Overdose Management

• Signs appear within 30 minutes to 3 hours after ingestion 5
• Early manifestations include nausea, vomiting, dizziness, slurred speech, blurred vision 5
• Severe overdose can cause respiratory distress, CNS depression, seizures, metabolic acidosis 5
• Treatment includes:
  • Pyridoxine administration on a gram-per-gram basis equal to isoniazid dose 5
  • Activated charcoal to decrease absorption 5
  • Ventilatory support as needed 5

Special Populations

Elderly Patients

• Higher risk of adverse effects, particularly hepatotoxicity 1
• More likely to develop peripheral neuropathy 6
• May require closer monitoring 1

Patients with Renal Insufficiency

• Higher risk of neurological side effects, including seizures 3
• Additional pyridoxine supplementation (50 mg/day) recommended 3
• May require dose adjustment 3

HIV-Infected Patients

• Generally tolerate isoniazid well 1
• Higher risk of peripheral neuropathy 4
• Pyridoxine supplementation strongly recommended 2, 4

Contraindications

• Severe hypersensitivity reactions 5
• Previous isoniazid-associated hepatic injury 5
• Severe adverse reactions such as drug fever, chills, arthritis 5
• Acute liver disease of any etiology 5

Remember that despite these side effects, isoniazid remains a relatively safe medication when properly monitored, with serious adverse events occurring in a small percentage of patients 7.