A Prospective Open‐Label Observational Study of a Buffered Soluble 70 mg Alendronate Effervescent Tablet on Upper Gastrointestinal Safety and Medication Errors: The GastroPASS Study

Abstract

Upper gastrointestinal (GI) side effects are a main reason for discontinuing bisphosphonate treatment, an important therapeutic option for osteoporosis patients. Consequently, the development of novel formulations with improved tolerability is warranted. In this multicenter prospective, observational, postauthorization safety study conducted in Italy and Spain, postmenopausal women (PMW) with osteoporosis (naïve to bisphosphonates) were treated weekly with a buffered soluble alendronate 70 mg effervescent (ALN-EFF) tablet (Binosto ® ) and followed for 12 AE 3 months. Information was collected on adverse events (AEs), medication errors, persistence, and compliance using the Morisky-Green questionnaire. Patients (N = 1028) aged 67 AE 9 years (mean AE SD) received ALN-EFF weekly. The cumulative incidence of upper GI AEs (oesophageal toxicity, gastritis, gastric ulcers, and duodenitis) related to ALN-EFF (primary endpoint) was 9.6% (95% confidence interval [CI] 7.9-11.6%), the vast majority being of mild intensity. The most frequently occurring upper GI AEs related to ALN-EFF were dyspepsia (2.7%), gastroesophageal reflux disease (2.4%), and nausea (2.2%). None of the relevant upper GI AEs listed in the primary endpoint and no serious AEs were reported. At least one medication error occurred in 29.9% (95% CI 27.1-32.8%) of patients. However, the majority of medication errors were associated with administration instructions applicable to any oral bisphosphonate and only seven medication errors were associated with the ALN-EFF formulation. ALN-EFF was discontinued in 209 of 1028 (20.3%) patients. The most frequent reasons for discontinuation were AEs related to ALN-EFF (46.9%) and patients' decision (42.6%). Compliance with ALN-EFF was high, reflected by a mean Morisky-Green score of 92.8 AE 18.6. PMW with osteoporosis treated with ALN-EFF in a real-world setting experienced few upper GI AEs. In addition, they had a low discontinuation and high compliance compared with other formulations, suggesting that ALN-EFF may increase patient satisfaction and therefore long-term adherence and efficacy.

Novel formulations of oral bisphosphonates in the treatment of osteoporosis

“…A prospective, observational, post-authorisation study in Italy and Spain examined the performance of a form of buffered alendronate (Binosto®) focusing on key outcomes of adverse events, medication errors, persistence and compliance, in a group of post-menopausal females (intention to treat n = 1084, safety cohort n = 1028, completed n = 873) over a 12-month period [ 59 ].…”

“…Gastro-intestinal adverse events were observed in 31% ( n = 319) participants and, of these, 85% ( n = 271) were upper gastro-intestinal. The cumulative incidence of all upper gastro-intestinal adverse events was 12.7%, with 9.6% specifically related to the effervescent, buffered alendronate (8% mild, 1.5% moderate, 0.2% severe but none of these adverse events were graded as serious) [ 59 ].…”

“…In terms of the specific symptoms or pathologies associated with these adverse effects the incidence rate was highest for nausea (IR = 2.1, 95% CI 1.4–3.2) followed by abdominal pain (IR = 1.2, 95% CI 0.6–2.1) and gastritis (IR = 0.8, 95% CI 0.4–1.6) with no reported gastric stenosis, ulceration, perforation or haemorrhage [ 59 ].…”

“…Medication errors were recorded in 30% of participants ( n = 307) including not waiting a sufficient time before consuming the first meal (10%), using a liquid other than water to dissolve the effervescent alendronate (9%) and an insufficient volume of water (< 30 ml) drunk following the consumption of the medication (7.6%) [ 59 ].…”

“…Approximately 80% of participants continued the effervescent alendronate through the duration of follow-up with the most common cause of discontinuation labelled as “patient decision” in 42.6% ( n = 89) of those who discontinued [ 59 ]. Persistence rates were therefore higher than that reported in bisphosphonates in a similar study in which 71.3% participants were taking a bisphosphonate at 6 months of follow-up.…”