What are the potential interactions between Bactrim (trimethoprim/sulfamethoxazole) and famotidine?

Bactrim and Famotidine Interaction

There is no clinically significant drug interaction between Bactrim (trimethoprim-sulfamethoxazole) and famotidine, and they can be safely used together. 1

Why These Drugs Are Compatible

• Famotidine is an H2-receptor antagonist that does not interact with the major pathways affected by trimethoprim-sulfamethoxazole 1

• The primary drug interactions of concern with Bactrim involve:

  • Drugs metabolized by cytochrome P450 enzymes 2
  • Antifolate medications (especially methotrexate) 1, 2
  • Drugs affecting renal potassium elimination 1, 2
  • Warfarin and other anticoagulants 2
  • Digoxin 2

• Famotidine does not fall into any of these high-risk categories and is not listed among the documented drug interactions with trimethoprim-sulfamethoxazole 1, 2

Important Caveat About Proton Pump Inhibitors vs H2 Blockers

• Proton pump inhibitors (PPIs) are specifically listed as having interactions with tetracyclines (not trimethoprim-sulfamethoxazole), but this does not apply to H2-receptor antagonists like famotidine 1

• The distinction is important: famotidine works through a different mechanism than PPIs and does not share the same interaction profile 1

Critical Monitoring When Using Bactrim (Regardless of Famotidine)

You must monitor electrolytes when prescribing Bactrim, as trimethoprim acts as a potassium-sparing diuretic similar to amiloride: 3, 4, 5

• Hyperkalemia risk is dose-dependent: patients taking >160 mg/day trimethoprim have 64.7% cumulative incidence versus 35.2% with ≤160 mg/day 3

• Hyponatremia can occur concurrently with hyperkalemia and may be severe and life-threatening 6

• Monitor serum potassium and sodium at baseline, 1-2 weeks after initiation, and every 4 months during therapy 1

• High-risk patients requiring extra vigilance:

  • Creatinine clearance <30 mL/min 1, 7
  • Concurrent use of ACE inhibitors, ARBs, or other potassium-sparing agents 1, 2
  • Elderly patients 2
  • Those taking NSAIDs 1

• Complete blood count monitoring is recommended to detect hematologic toxicity 2

• Discontinue immediately if rash develops due to risk of Stevens-Johnson syndrome or toxic epidermal necrolysis 2