Should bisphosphonates be taken with food or without food?

Oral Bisphosphonates Must Be Taken on an Empty Stomach

Oral bisphosphonates should be taken on an empty stomach with a full glass of water, and patients must remain upright for at least 30 minutes afterward without consuming any food or other medications during this time. 1, 2

Administration Requirements for Oral Bisphosphonates

Proper administration of oral bisphosphonates is critical for both absorption and safety:

• Timing: Take upon waking in the morning
• Method: Take with a full glass (6-8 oz) of plain water only
• Position: Remain upright (sitting or standing) for at least 30 minutes after taking
• Fasting requirements:
  • No food or beverages (except plain water) for at least 30 minutes after taking the medication
  • No calcium supplements for at least 2 hours after taking bisphosphonates 1

Rationale for These Requirements

1. Poor absorption: Oral bisphosphonates have very low bioavailability (less than 1% for nitrogen-containing bisphosphonates) 3
2. Food interactions: When taken with food or beverages, bisphosphonates form complexes that cannot be absorbed 3
3. Risk of esophageal irritation: Remaining upright helps prevent the medication from lodging in the esophagus 1, 2

Potential Consequences of Incorrect Administration

Failure to follow proper administration instructions can lead to:

1. Reduced efficacy: Taking with food can reduce absorption by up to 90%, potentially leading to treatment failure 3
2. Increased risk of GI side effects: The most common adverse effects include 1, 2:
   • Esophageal irritation and inflammation
   • Dysphagia
   • Gastric ulcers
   • Abdominal pain

Risk Factors for GI Side Effects

Patients at higher risk for GI complications include those who 2:

• Take medication with insufficient water
• Lie down within 30 minutes after taking the medication
• Have pre-existing esophageal disorders
• Continue medication after onset of symptoms

Management Recommendations

1. Patient education: Clearly explain administration requirements
2. Monitoring: Instruct patients to discontinue and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain, or new/worsening heartburn 2
3. Calcium supplementation: Calcium and vitamin D supplementation is recommended for most patients on bisphosphonates, but calcium should be taken at least 2 hours after the bisphosphonate 1
4. Alternative formulations: For patients who cannot tolerate or comply with oral bisphosphonate requirements, consider:
   • Intravenous bisphosphonates (zoledronic acid, ibandronate) 1
   • Newer formulations such as enteric-coated delayed-release risedronate with EDTA that may eliminate the need for fasting 3

Special Considerations

• Dental health: Complete any necessary dental work before starting bisphosphonate therapy to reduce the risk of osteonecrosis of the jaw 1
• Renal function: Monitor renal function prior to starting IV bisphosphonates and throughout treatment 1
• Vitamin D status: Correct vitamin D deficiency before initiating bisphosphonates to prevent hypocalcemia 1

By following these administration guidelines, patients can maximize the effectiveness of bisphosphonate therapy while minimizing the risk of adverse effects.