Apo-Alendronate Drug Interactions

Overview: Animal studies have demonstrated that alendronate is highly concentrated in bone and is retained only minimally in soft tissue. No metabolites have been detected. Although alendronate is bound approximately 78% to plasma protein in humans, its plasma concentration is so low after oral dosing that only a small fraction of plasma-binding sites is occupied, resulting in a minimal potential for interference with the binding of other drugs. Alendronate is not excreted through the acidic or basic transport systems of the kidney in rats, and thus it is not anticipated to interfere with the excretion of other drugs by those systems in humans. In summary, APO-ALENDRONATE is not expected to interact with other drugs based on effects on protein binding, renal excretion, or metabolism of other drugs.
Drug-Drug Interactions: If taken at the same time it is likely that calcium supplements, antacids, and other oral medications will interfere with absorption of APO-ALENDRONATE. Therefore, patients must wait at least one-half hour after taking APO-ALENDRONATE before taking any other oral medication.
Intravenous ranitidine was shown to double the bioavailability of oral alendronate. The clinical significance of this increased bioavailability and whether similar increases will occur in patients given oral H2-antagonists is unknown.
Concomitant use of hormone replacement therapy (HRT [estrogen±progestin]) and alendronate was assessed in two clinical studies of one or two years' duration in postmenopausal osteoporotic women. Combined use of alendronate and HRT resulted in greater increases in bone mass, together with greater decreases in bone turnover, than seen with either treatment alone. In these studies, the safety and tolerability profile of the combination was consistent with those of the individual treatments (see ADVERSE REACTIONS). The studies were too small to detect antifracture efficacy, and no significant differences in fracture incidence among the treatment groups were found.
Specific interaction studies were not performed. Alendronate was used in osteoporosis studies in men, postmenopausal women, and glucocorticoid users, with a wide range of commonly prescribed drugs without evidence of clinical adverse interactions.
In clinical studies, the incidence of upper gastrointestinal adverse events was increased in patients receiving daily therapy with dosages of alendronate greater than 10 mg and acetylsalicylic acid-containing products. This was not observed in a study with alendronate 70 mg once weekly.
Alendronate may be administered to patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). In a 3-year, controlled, clinical study (n=2027) during which a majority of patients received concomitant NSAIDs, the incidence of upper gastrointestinal adverse events was similar in patients taking alendronate 5 or 10 mg/day compared to those taking placebo. However, since NSAID use is associated with gastrointestinal irritation, caution should be used during concomitant use with APO-ALENDRONATE.