The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate, respectively, had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, compared with those on weekly alendronate.
“The results of this analysis suggest that persistency rates are not improved by monthly dosing of oral bisphosphonates versus weekly dosing,” the authors wrote.
In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonate therapy. The data come from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. For this study, the researchers contracted with a large pharmacy with more than 3,000 stores in 28 states.
Potential participants were identified by their retail pharmacy dispensing records. Patients were initially defined as persisters if they filled their bisphosphonate prescriptions at least five times in a 17-month period. Persistence was confirmed using the interview process. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.
Belief in the efficacy of osteoporosis drugs and the absence of side effects and drug interactions were strong determinants of persistence with bisphosphonate therapy. In all, 93% of weekly persisters reported belief in the drug's effectiveness, compared with 88% of monthly persisters. In both groups, 83% reported an absence of side effects.
However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Weekly and monthly persisters were equally likely to report out-of-pocket costs and remembering to take the bisphosphonates as their biggest problems. Altogether, 45% of weekly persisters and 52% of monthly persisters reported out-of-pocket costs being a problem. And 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.
Dosing frequency was not cited as a problem by many in either group—13% of weekly persisters and 7% of monthly persisters. “The DASH study suggests that the major drivers of persistency with bisphosphonates are belief in the effectiveness of the therapy and the lack of side effects and drug interactions, not dosing frequency,” the researchers wrote.
Compliance is key to successful treatment with these drugs because bioavailability is notoriously poor.
Under optimal conditions—when patients follow dosing instructions perfectly—bioavailability of oral bisphosphonates is minuscule. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours before breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.
But optimal conditions are demanding for a patient. Patients on alendronate and risedronate should take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications, and they should not lie down for 30 minutes after taking either of these drugs.
Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients should not to lie down for 60 minutes after taking the drug.
However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves greatly the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by about 40% when taken either 30 minutes or 1 hour before breakfast, when compared with dosing 2 hours before eating. The package labeling for alendronate also notes that “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice when alendronate is taken reduces bioavailability by about 60% as well.
For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, compared with dosing in the fasting state. Dosing 1 hour before breakfast reduces the extent of absorption by 30%, compared with dosing in the fasting state. Dosing either half an hour before breakfast or 2 hours after dinner results in a similar extent of absorption.
For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, in comparison with that observed in fasted patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are taken less than 60 minutes after an ibandronate dose.