What are the potential interactions with famotidine (histamine-2 (H2) blocker) and other medications?

Famotidine Drug Interactions

Famotidine has minimal drug interactions compared to other H2 receptor antagonists, making it a preferred choice when drug interaction concerns exist. 1

Pharmacokinetic Profile and Metabolism

Famotidine is a histamine H2-receptor antagonist that undergoes minimal first-pass metabolism, with 25-30% of an oral dose recovered in urine as unchanged compound. The only metabolite identified in humans is the S-oxide. Famotidine is eliminated primarily through renal excretion (65-70%) with a smaller portion through metabolic pathways (30-35%) 2.

Key characteristics that affect its interaction profile:

• Bioavailability: 40-45% (may be slightly increased by food or decreased by antacids)
• Protein binding: Only 15-20% (relatively low)
• Half-life: 2.5-3.5 hours
• Minimal binding to cytochrome P450 enzymes

Advantages Over Other H2 Blockers

Famotidine has a significant advantage over other H2 receptor antagonists regarding drug interactions:

• Unlike cimetidine: Famotidine does not bind to the cytochrome P-450 system and therefore has low potential to interact with medications metabolized through this pathway 1
• Unlike ranitidine: While ranitidine interacts weakly with cytochrome P-450, famotidine has even less interaction potential 1
• Safety profile: Famotidine has not been associated with clinically significant drug interactions in extensive clinical experience 3

Specific Medication Interactions

Antiplatelet Medications

• Clopidogrel: Unlike PPIs which may reduce clopidogrel's effectiveness by inhibiting CYP2C19, famotidine does not interact with the antiplatelet activity of clopidogrel 1
• The FDA specifically notes there is no evidence that H2 blockers like famotidine interfere with the antiplatelet activity of clopidogrel 1

pH-Dependent Drug Absorption

• Dasatinib: Famotidine may reduce dasatinib absorption due to pH-dependent solubility. If antacid therapy is needed with dasatinib, administer at least 2 hours before or 2 hours after dasatinib 1
• Ledipasvir: H2-receptor antagonists can decrease concentrations of ledipasvir. If needed, famotidine should not exceed 40 mg and should be given simultaneously or 12 hours apart from ledipasvir 1
• Glecaprevir/pibrentasvir: The solubility decreases as pH increases, though specific guidance for famotidine is not provided 1

Transporter Interactions

• OAT1 and OAT3: Famotidine is a substrate for OAT1 and OAT3. Coadministration with probenecid (an OAT1/OAT3 inhibitor) increases famotidine serum concentration 2
• MATE-1: Famotidine is an inhibitor of MATE-1 in vitro, but no clinically significant interaction with metformin has been observed 2

Enzyme Interactions

• CYP1A2: Famotidine is a weak CYP1A2 inhibitor, but this has minimal clinical significance 2
• Other CYP enzymes: Unlike cimetidine, famotidine does not inhibit CYP1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 1, 4

Bile Acid Sequestrants

• If co-administered with bile acid sequestrants, separate administration times to minimize potential for reduced absorption 1

Clinical Considerations

1. Patient populations requiring special attention:

   • Renal impairment: Famotidine exposure increases at least 2-fold in moderate renal impairment and 5-fold in severe renal impairment, requiring dose adjustment 2
   • Pediatric patients: Bioavailability is slightly higher than in adults 2

2. Monitoring recommendations:

   • Routine monitoring for drug interactions is generally not necessary with famotidine due to its minimal interaction profile
   • Focus monitoring on therapeutic effect rather than drug interactions

Common Pitfalls to Avoid

1. Confusing famotidine with cimetidine: Cimetidine has numerous drug interactions that famotidine does not share. Avoid assuming all H2 blockers have similar interaction profiles.

2. Overlooking pH-dependent drug interactions: While famotidine has minimal metabolic interactions, it can affect absorption of drugs requiring acidic gastric pH for dissolution.

3. Unnecessary concern about antiplatelet therapy: Unlike PPIs, famotidine does not significantly affect clopidogrel efficacy and can be a safer alternative for patients requiring dual antiplatelet therapy.

4. Rare hepatic reactions: Although extremely rare, hepatitis has been reported with famotidine use 5, suggesting monitoring liver function may be prudent in patients with pre-existing liver disease.

Famotidine's minimal drug interaction profile makes it an excellent choice when drug interactions are a concern, particularly in patients on multiple medications or those taking drugs with narrow therapeutic indices.