How are extended release (ER) medications affected in patients who have undergone roux-en-Y gastric bypass surgery?

Impact of Roux-en-Y Gastric Bypass on Extended Release Medications

Extended release medications should be avoided in patients who have undergone Roux-en-Y gastric bypass (RYGB) surgery due to unpredictable absorption and potential for therapeutic failure. 1, 2

Anatomical and Physiological Changes Affecting Drug Absorption

RYGB creates significant anatomical and physiological alterations that impact medication absorption:

• Creation of a small gastric pouch (approximately 20 mL)
• Bypassing of the duodenum and proximal jejunum
• Reduced gastric acid production
• Altered gastric emptying time
• Changes in intestinal transit time
• Reduced surface area for absorption

These changes particularly affect extended release (ER) formulations which are designed to be absorbed gradually throughout the gastrointestinal tract 2.

Impact on Specific Extended Release Medications

Documented Effects:

• Antipsychotics: ER formulations show significantly reduced absorption after RYGB. In one case study, lurasidone levels dropped from 20 ng/mL pre-surgery to 8.1 ng/mL post-surgery. Similarly, paliperidone ER resulted in subtherapeutic levels (1.1 ng/mL) after RYGB 3.

• Anticoagulants: Dabigatran has shown impaired absorption following RYGB, potentially leading to subtherapeutic anticoagulation and increased risk of thromboembolic events 4.

• Proton Pump Inhibitors: Omeprazole shows faster absorption but decreased overall exposure (AUC) after RYGB, often requiring dose adjustments 5, 6.

Variable Effects:

• Antidepressants: Venlafaxine ER showed no statistically significant change in bioavailability after RYGB in a small study, suggesting some ER medications may maintain therapeutic levels 7.

Clinical Recommendations

1. Medication Selection:

   • Prefer immediate-release (IR) formulations over ER formulations
   • Consider non-oral routes of administration when available (transdermal, injectable)
   • For psychiatric medications, non-oral antipsychotic formulations may be preferred 3

2. Monitoring:

   • Implement therapeutic drug monitoring when available
   • Monitor for signs of therapeutic failure or toxicity
   • Consider measuring drug levels before and after surgery for medications with narrow therapeutic windows

3. Dosing Adjustments:

   • Be prepared to increase doses of medications showing decreased absorption
   • For medications like omeprazole, higher doses may be needed to achieve therapeutic effect 6
   • Consider dividing daily doses rather than using once-daily ER formulations

4. Iron Supplementation:

   • IV iron is preferred over oral supplementation for treating iron deficiency anemia after RYGB 1
   • This principle applies to other nutrients and medications with primary absorption sites in the bypassed segments

Special Considerations

• Liquid Formulations: When using liquid formulations, avoid those containing non-absorbable sugars due to risk of dumping syndrome 1

• Capsules: Open capsules if allowed according to product characteristics to improve absorption 1

• Therapeutic Failure Risk: Be particularly vigilant with medications where therapeutic failure carries high risk (anticoagulants, antiepileptics, immunosuppressants)

• Long-term Follow-up: Regular medication reviews are essential as absorption patterns may change over time as the post-surgical anatomy adapts

The evidence strongly suggests that RYGB significantly alters drug absorption patterns, with extended release formulations being particularly vulnerable to unpredictable absorption. Clinicians should carefully evaluate the necessity of each medication and consider alternative formulations or routes of administration to ensure therapeutic efficacy.