Pamidronate: an unrecognized problem in gastrointestinal tolerability

Area of Science:

• Bone Metabolism and Pharmacology
• Gastroenterology
• Clinical Therapeutics

Background:

• Pamidronate (aminohydroxypropylidine bisphosphonate, APD) is recognized for treating Paget's disease and is considered for osteoporosis.
• A novel time-release formulation of pamidronate was investigated for postmenopausal osteoporosis.

Purpose of the Study:

• To evaluate the efficacy and safety of a new time-release pamidronate preparation in postmenopausal osteoporosis.
• To assess the incidence of adverse events, specifically esophagitis, associated with the novel formulation.

Main Methods:

• A placebo-controlled, double-masked study was conducted.
• Initial trials used a rapidly dissolving gelatin capsule formulation.
• Subsequent trials utilized a standard tablet preparation.

Main Results:

• Four cases of esophagitis occurred in 49 patients using the gelatin capsule formulation.
• One additional case of erosive esophagitis was observed in 40 patients using the tablet preparation.
• Esophagitis was confirmed by endoscopy and resolved upon pamidronate discontinuation and antacid use.

Conclusions:

• The investigated time-release pamidronate preparations were associated with a significant risk of esophagitis.
• Further investigation into the safety profile of novel bisphosphonate formulations is warranted.
• Alternative formulations or administration routes may be necessary to mitigate gastrointestinal side effects.