Drug Interactions and Contraindications with Famotidine and Xifaxan (Rifaximin)
Patients taking famotidine should avoid concomitant use with dasatinib, delavirdine mesylate, cefditoren, fosamprenavir, and tizanidine, while rifaximin has minimal drug interactions due to its non-systemic absorption. 1
Critical Famotidine Drug Interactions
Absolutely Contraindicated Medications
- Dasatinib (cancer medication) - famotidine significantly reduces absorption due to decreased gastric acidity 1
- Delavirdine mesylate (HIV medication) - requires acidic environment for absorption 1
- Cefditoren (antibiotic) - absorption impaired by acid suppression 1
- Fosamprenavir (HIV protease inhibitor) - concomitant use not recommended 1
- Tizanidine (muscle relaxant) - famotidine inhibits CYP1A2 metabolism, causing dangerous accumulation leading to hypotension, bradycardia, and excessive drowsiness 1
Medications Requiring Careful Monitoring
Famotidine reduces gastric acidity, which impairs absorption of the following medications that require acidic pH 1:
- Atazanavir (HIV medication)
- Erlotinib (cancer medication)
- Ketoconazole and itraconazole (antifungal medications)
- Ledipasvir/sofosbuvir (hepatitis C treatment)
- Nilotinib (cancer medication)
- Rilpivirine (HIV medication)
For these medications, consult their specific prescribing information for timing adjustments or alternative strategies 1.
Rifaximin (Xifaxan) Drug Interactions
Rifaximin has essentially no clinically significant drug interactions because it is not absorbed systemically from the gastrointestinal tract. 2, 3, 4 This non-systemic absorption is precisely why rifaximin is the preferred antibiotic for SIBO treatment - it minimizes systemic antibiotic resistance risk while maintaining broad-spectrum intestinal coverage 2, 3.
No Documented Interactions
- Rifaximin demonstrates no clinically relevant interactions with other medications due to negligible systemic absorption 4
- Safe to use with immunomodulators and biologics commonly prescribed for Crohn's disease 5, 6, 7
Special Considerations for Crohn's Disease and SIBO
Medication Continuation During Treatment
- Continue all IBD maintenance medications (biologics, immunomodulators, 5-ASA) during rifaximin treatment - do not stop without discussing with the IBD team due to flare risk 8
- Avoid NSAIDs if possible, as they increase gastrointestinal bleeding risk and may exacerbate Crohn's disease 8
Proton Pump Inhibitor Consideration
- Gastric acid suppression is a well-established risk factor for SIBO development 9
- If the patient is taking PPIs (omeprazole, esomeprazole, etc.), consider switching to famotidine as it maintains some protective gastric acidity while providing symptom relief 9
- However, famotidine itself can predispose to SIBO recurrence if used long-term, so use the lowest effective dose 9
Adjunctive Medications That Are Safe
- Bile salt sequestrants (cholestyramine, colesevelam) - safe to use if bile salt malabsorption occurs 2, 9
- Antidiarrheal agents (loperamide) - safe for symptomatic relief 2
- Vitamin supplementation (B12, fat-soluble vitamins) - recommended during and after SIBO treatment 2, 3
Common Pitfalls to Avoid
- Do not assume all antibiotics are safe together - while rifaximin has no interactions, famotidine significantly affects absorption of many medications 1
- Do not stop IBD medications during SIBO treatment without specialist consultation, as disease flare risk outweighs temporary treatment concerns 8
- Monitor for Clostridioides difficile with prolonged or repeated rifaximin courses, though risk is lower than with systemic antibiotics 2, 9
- Avoid combining multiple acid suppressants - if using famotidine, do not add PPIs as this increases SIBO recurrence risk 9