What are the side effects of anti-tuberculosis (TB) medications?

Side Effects of Anti-TB Medications

Anti-tuberculosis medications commonly cause a range of side effects that can significantly impact morbidity, mortality, and quality of life, with hepatotoxicity, neurotoxicity, and sensory impairments being the most concerning adverse reactions requiring careful monitoring and management. 1

First-Line Anti-TB Drugs and Their Major Side Effects

Isoniazid (INH)

• Hepatotoxicity: Most serious adverse effect, with incidence of 0.5-1% (higher in females and elderly) 1
• Peripheral neuropathy: Can be prevented with pyridoxine (10 mg/day) supplementation 1
• Other side effects: Rash, fever, drug interactions with phenytoin and carbamazepine 1

Rifampin (RIF)

• Hepatotoxicity: Less common than with INH but can occur
• Gastrointestinal upset: Nausea, vomiting, abdominal pain 2
• "Flu-like syndrome": Fever, chills, headache (more common with intermittent dosing) 1
• Drug interactions: Significant inducer of hepatic enzymes affecting many medications including:
  • Oral contraceptives (reduced effectiveness)
  • Methadone (reduced levels)
  • Warfarin, corticosteroids, anticonvulsants 1
• Rare but serious: Thrombocytopenia, hemolysis, renal failure, shock 1

Pyrazinamide (PZA)

• Hepatotoxicity: Can be severe and potentially fatal 3
• Joint pain/arthralgia: Often due to hyperuricemia 3
• Highest incidence of adverse effects: 1.48 per 100 person-months of exposure (significantly higher than other first-line drugs) 4

Ethambutol (EMB)

• Optic neuritis: Dose-related and most serious adverse effect 1, 5
  • Symptoms: Blurred vision, red/green color blindness, central scotomata
  • Risk increases with doses >15 mg/kg/day and with renal impairment
  • Visual acuity must be tested before and monthly during treatment 5
  • Should be stopped immediately if visual symptoms appear 1
• Other side effects: Peripheral neuritis, rash, abdominal discomfort 5

Streptomycin (SM)

• Ototoxicity: Irreversible damage to vestibular branch of eighth cranial nerve 1
  • Symptoms: Vertigo, ataxia, nystagmus, hearing loss
• Nephrotoxicity: Especially in patients with pre-existing renal insufficiency 1
• Contraindicated in: Pregnancy, auditory nerve impairment, myasthenia gravis 1

Second-Line Anti-TB Drugs and Their Side Effects

Cycloserine

• Neuropsychiatric effects: Psychosis, depression, headache, seizures, vertigo 1
• Higher risk in: Alcoholics and patients receiving >500 mg/day 1

Ethionamide/Prothionamide

• Gastrointestinal intolerance: Abdominal pain, nausea, vomiting (most frequent) 1
• Hepatotoxicity and potential hyperglycemia in diabetics 1

Aminoglycosides (Kanamycin, Amikacin) and Polypeptides (Capreomycin)

• Nephrotoxicity, ototoxicity, neuromuscular blockade 1
• Require dose reduction in renal impairment 1

Fluoroquinolones (Ofloxacin, Ciprofloxacin)

• Side effects relatively rare (3-7%) and usually mild 1
• Include: Abdominal pain, nausea, vomiting, dizziness, headache, elevated liver enzymes 1
• Caution in children: May impair growth and damage growing cartilage 1

Risk Factors for Developing Side Effects

• Age over 60 years: 2.9 times higher risk of major side effects 4
• Female sex: 2.5 times higher risk 4
• HIV-positive status: 3.8 times higher risk 4
• Asian birthplace: 2.5 times higher risk 4

Management of Common Side Effects

Gastrointestinal Side Effects

• For vomiting:
  • Administer medications with food rather than on empty stomach 2
  • Change timing of dosing (e.g., evening instead of morning) 2
  • Split the dose of the suspected offending drug 2
  • Monitor hydration status and serum potassium if vomiting is severe 2

Hepatotoxicity

• Warning signs: Abdominal pain, jaundice, vomiting 2
• Action: Immediately stop hepatotoxic drugs (INH, RIF, PZA) and evaluate 2

Visual Disturbances (Ethambutol)

• Monitoring: Test visual acuity before starting therapy and monthly during treatment 5
• Action: Stop ethambutol immediately if visual symptoms appear 1, 5
• Recovery usually occurs over weeks to months after discontinuation 5

Important Considerations

1. Never ignore severe vomiting as it can lead to dehydration, electrolyte imbalances, and poor medication absorption 2

2. Distinguish between simple medication-related side effects and serious toxicity (e.g., hepatitis) 2

3. Minor side effects are common early in treatment and often resolve with time 2

4. First-line TB drugs should not be discontinued due to minor side effects whenever possible 2

5. Therapeutic drug monitoring may be beneficial for patients who:

   • Are slow to respond to treatment
   • Have drug-resistant TB
   • Are at risk of drug-drug interactions
   • Have concurrent disease states 6

By understanding and properly managing these side effects, clinicians can help ensure successful treatment outcomes while minimizing the risk of treatment discontinuation and the development of drug resistance.