What medication for acid reflux won't interfere with Xgeva (denosumab) or Xtandi (enzalutamide)?

Acid Reflux Medication Selection for Patients on Xgeva and Xtandi

H2-receptor antagonists (H2RAs) such as famotidine or standard-dose proton pump inhibitors (PPIs) like omeprazole are appropriate choices for acid reflux in patients taking Xgeva (denosumab) and Xtandi (enzalutamide), as these acid-suppressing medications do not have clinically significant drug interactions with either cancer therapy.

Rationale for Safety with These Agents

No Direct Drug Interactions

• Xgeva (denosumab) is a monoclonal antibody that does not undergo hepatic metabolism and has no known cytochrome P450 interactions, making it compatible with both PPIs and H2RAs 1
• Xtandi (enzalutamide) is a CYP3A4 inducer and substrate, but neither PPIs nor H2RAs are significantly affected by or affect CYP3A4 activity in clinically meaningful ways 1

Recommended Treatment Algorithm

For Initial Therapy:

• Start with a standard-dose PPI (omeprazole 20mg, lansoprazole 30mg, or esomeprazole 20mg) taken 30-60 minutes before a meal once daily for 4-8 weeks 1
• If cost or access is a concern, famotidine 20mg twice daily represents an effective alternative, though PPIs demonstrate superior efficacy for erosive esophagitis 1, 2

For Inadequate Response:

• Escalate to twice-daily PPI dosing if symptoms persist after 4-8 weeks 1
• The combination of an H2RA at bedtime with daytime PPI can address nocturnal acid breakthrough, though tachyphylaxis to H2RAs develops within 6 weeks 3, 4

For Maintenance:

• Once symptoms are controlled, taper to the lowest effective dose 1
• Long-term PPI use should be accompanied by awareness of potential risks including impaired calcium absorption (relevant given Xgeva's mechanism), vitamin B12 deficiency, and increased fracture risk 5

Important Clinical Considerations

Calcium Absorption Concerns

• Critical caveat: Patients on Xgeva require adequate calcium and vitamin D supplementation to prevent hypocalcemia 1
• PPIs can reduce calcium absorption by decreasing gastric acid needed for calcium carbonate dissolution 5
• Mitigation strategy: Use calcium citrate rather than calcium carbonate for supplementation, as citrate does not require acid for absorption, or take calcium carbonate with meals when acid production is highest 1

Avoid Antacids with Polyvalent Cations

• Do not use aluminum, magnesium, or calcium-containing antacids simultaneously with other medications, as they can interfere with drug absorption 3
• If antacids are needed for breakthrough symptoms, separate administration by at least 2 hours from other medications 3

Agents to Avoid or Use with Caution

Prokinetic Agents:

• Metoclopramide and cisapride have limited evidence for reflux management and carry additional side effect profiles 5
• These are not first-line and should be reserved for documented motility disorders 5

Potassium-Competitive Acid Blockers (P-CABs):

• Vonoprazan and other P-CABs should not be used as initial therapy given higher costs, limited long-term safety data, and lack of demonstrated superiority over standard PPIs for most indications 5
• Reserve P-CABs for PPI-refractory cases only 5

Monitoring Recommendations

• Assess symptom response after 4-8 weeks of therapy 1
• If symptoms persist despite twice-daily PPI, perform objective testing (endoscopy and pH monitoring off PPI) to confirm GERD diagnosis before further escalation 5, 1
• Monitor serum calcium levels regularly in patients on Xgeva, particularly when initiating or escalating acid suppression 1
• Avoid empiric long-term PPI therapy without objective confirmation of GERD diagnosis 1