Pamidronate: An unrecognized problem in gastrointestinal tolerability

Abstract

Pamidronate (aminohydroxypropylidine bisphosphonate, APD) is an effective agent for treatment of Paget's disease of bone, and it has also been thought to be effective for treatment of osteoporosis. We desired to study a newer, time-release preparation of pamidronate, and carried out a placebo-controlled, double-masked study of postmenopausal osteoporosis. The original formulation was in a rapidly dissolving gelatin capsule. We encountered four episodes of esophagitis in 49 enrolled patients. We therefore discontinued treatment with this preparation and later began the study again using a standard tablet preparation. We encountered an additional case of erosive esophagitis in 1 patient of 40 receiving this tablet preparation. No patient was receiving concomitant medication which could cause esophagitis. Two of the patients gave a past history of hiatal hernia and 1 gave a history of gastric ulcer 27 years previously. The diagnosis of esophagitis was confirmed in all cases by endoscopy. Healing of the esophagitis promptly ensued after discontinuation of the pamidronate and the use of antacid medication.

Bisphosphonates: Mechanisms of Action

“…The oral administration of bisphosphonates, especially those with a primary amine, can be accompanied by esophageal and gastrointestinal side effects such as nausea, dyspepsia, vomiting, gastric pain, and diarrhea, and sometimes even ulceration (129,130,274). These adverse events have decreased since patients began ingesting the drug with adequate water and without reclining after its intake to minimize esophageal reflux.…”

“…These appeared to be more pronounced for the aminobisphosphonates. It is now known that pamidronate (129), as well as alendronate (130), can, when given orally, induce serious adverse esophageal effects such as esophagitis, erosions, and ulcerations.…”

Tratamento da doença de Paget óssea: importância do ácido zoledrônico

“…É mais utilizado por via parenteral na dose de 60 mg em uma única infusão em casos de pouca atividade da doença (fosfatase alcalina 2 a 3 vezes acima do valor normal máximo). Doses maiores (90-180 mg) podem ser usadas em intensidade moderada a severa, em infusões por 3 dias seguidos ou semanais (23). A dose máxima utilizada em um dia é 90 mg, diluída em soro glicosado ou fisiológico, durante 4-6 horas.…”

Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis

“…In contrast, the more severe side effects associated with esophageal events such as ulceration are rare but potentially more serious, and were noted in particular after giving oral pamidronate 62 or alendronate. 63 In terms of practical management, the interference of absorption by food as well as these esophageal problems are minimized in patients taking oral bisphosphonates on an empty stomach, first thing in the morning, with sufficient plain water, while remaining in an upright position without eating or further drinking for at least 30 minutes (60 minutes in the case of ibandronate).…”