Which anti-tuberculosis treatments (ATT) most commonly cause gastritis?

Which Anti-Tuberculosis Treatments Most Commonly Cause Gastritis

Among anti-tuberculosis drugs, p-aminosalicylic acid (PAS) and ethionamide are the agents most commonly associated with gastrointestinal distress and gastritis-like symptoms, with PAS causing gastrointestinal intolerance in approximately 11% of patients and ethionamide commonly causing profound gastrointestinal side effects including nausea, vomiting, and abdominal pain. 1

First-Line Anti-Tuberculosis Drugs

Gastrointestinal reactions are common with first-line drugs, especially early in therapy:

• Rifampin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol can all cause epigastric distress or nausea, particularly in the first few weeks of treatment 1
• These gastrointestinal symptoms are typically mild and manageable without drug discontinuation 1
• The optimum management approach is to administer medications at bedtime or with meals, or use antacids rather than discontinuing therapy 1
• Administration with food is preferable to splitting doses or changing to second-line drugs, as the effects of food on absorption are of little clinical significance 1

Second-Line Anti-Tuberculosis Drugs

p-Aminosalicylic Acid (PAS)

PAS causes the highest rate of gastrointestinal distress among anti-TB medications:

• Gastrointestinal distress is the most common side effect of PAS 1
• In a large study of INH and PAS, 11% of patients had drug toxicity, with the majority being gastrointestinal intolerance to PAS 1
• The incidence of gastrointestinal side effects is lower with reduced doses (8 g daily) and with the granular formulation compared to tablets 1
• The granules do not need to be taken with acidic food as previously thought 1

Ethionamide

Ethionamide commonly causes profound gastrointestinal effects:

• Gastrointestinal side effects include metallic taste, nausea, vomiting (often severe), loss of appetite, and abdominal pain 1
• Symptoms may improve if doses are taken with food or at bedtime 1
• The single daily dose can be given at bedtime or with the main meal to minimize symptoms 1

Fluoroquinolones (Levofloxacin)

Fluoroquinolones cause relatively mild gastrointestinal symptoms:

• Nausea and bloating occur in only 0.5-1.8% of patients taking levofloxacin 1
• This represents a significantly lower incidence compared to PAS and ethionamide 1

Clinical Management Algorithm

For patients experiencing gastrointestinal symptoms on anti-TB therapy:

1. First, rule out hepatotoxicity by checking liver function tests (ALT, AST, bilirubin, alkaline phosphatase) if there is any combination of unexplained nausea, vomiting, or abdominal pain 1

2. For mild symptoms without hepatotoxicity:

   • Change timing of medication administration to bedtime 1
   • Administer with meals (absorption effects are clinically insignificant) 1
   • Use antacids, which have less impact on drug absorption than food 1

3. Never discontinue first-line drugs (especially rifampin) for minor gastrointestinal side effects 1

4. For second-line drugs causing severe symptoms:

   • PAS: Consider dose reduction to 8 g daily or ensure use of granular formulation 1
   • Ethionamide: Administer at bedtime or with main meal, consider divided dosing 1

Important Caveats

• Gastrointestinal symptoms must be distinguished from drug-induced hepatitis, which requires immediate cessation of hepatotoxic drugs (INH, RIF, PZA) 1
• Drug-induced hepatitis is defined as AST >3× upper limit of normal with symptoms, or >5× upper limit of normal without symptoms 1
• The overall prevalence of adverse drug reactions with first-line drugs ranges from 8.0% to 85%, with most occurring in the intensive phase 2
• Among first-line drugs, pyrazinamide has the highest incidence of major adverse effects at 1.48 per 100 person-months, though this primarily reflects hepatotoxicity rather than gastrointestinal symptoms 3