What percentage of Fosamax (alendronate) users discontinue the drug?

Fosamax (Alendronate) Discontinuation Rates

Approximately 9% of Fosamax users discontinue the drug due to adverse events in clinical trials, though real-world discontinuation rates may be higher.

Clinical Trial Discontinuation Data

Treatment of Postmenopausal Osteoporosis

In the pivotal osteoporosis treatment trials, 8.9% of patients discontinued alendronate due to clinical adverse events compared to 9.5% in the placebo group 1. This finding is notable because it demonstrates that discontinuation rates were actually slightly lower than placebo, suggesting that many discontinuations may be unrelated to the medication itself.

For weekly dosing regimens:

• Alendronate 70 mg once weekly: Discontinuation rates were similar to daily dosing, with the overall safety profile being comparable 1
• The weekly formulation was developed specifically to improve adherence and tolerability

Prevention Studies

In osteoporosis prevention trials with lower-risk populations:

• 7.5% of patients on alendronate 5 mg/day discontinued therapy due to adverse events versus 5.7% on placebo 1
• For weekly alendronate 35 mg, discontinuation patterns were similar to the 5 mg daily regimen 1

Special Populations

In men with osteoporosis, discontinuation rates were:

• 2.7% for alendronate 10 mg/day versus 10.5% for placebo (2-year study) 1
• 6.4% for weekly alendronate 70 mg versus 8.6% for placebo (1-year study) 1

In glucocorticoid-induced osteoporosis, the discontinuation profile was consistent with postmenopausal osteoporosis studies 1.

Real-World Discontinuation Patterns

Real-world persistence data suggests substantially higher discontinuation rates than clinical trials. In a retrospective analysis:

• 68% of patients on generic alendronate remained on therapy at 12 months (implying 32% discontinued) 2
• 84% of patients on branded Fosamax remained on therapy at 12 months (16% discontinued) 2

This discrepancy between clinical trial and real-world data is clinically important, as it suggests that actual discontinuation rates in practice may be 2-4 times higher than reported in controlled trials 2.

Primary Reasons for Discontinuation

The most common adverse events leading to discontinuation include 1:

• Gastrointestinal symptoms: Diarrhea (1.6%), though upper GI symptoms like dyspepsia and abdominal pain are more common overall
• Headaches (1.0%)
• Esophageal adverse events (reported in post-marketing surveillance, though rare in trials)

Important Clinical Caveats

The discontinuation rate varies significantly based on:

• Formulation: Generic alendronate shows higher discontinuation rates (32% at 1 year) compared to branded products (16% at 1 year) 2, possibly due to differences in gastrointestinal tolerability
• Dosing frequency: Weekly dosing was developed to improve adherence, though discontinuation rates in trials were similar to daily dosing 1
• Patient selection: Clinical trials exclude many patients with pre-existing GI conditions, whereas real-world populations include these higher-risk individuals 1

A critical finding is that serious adverse events were actually less common with alendronate than placebo in some analyses (1.8% all-cause mortality in both groups), suggesting the medication is generally well-tolerated when used appropriately 1.