Once-Weekly Alendronate Tablets
Pharmacology Update
Once-Weekly Alendronate Tablets
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Merck & co. has received fda approval to market once-a-week doses of alendronate for the treatment and prevention of osteoporosis. Alendronate is a bisphosphonate that inhibits bone resorption. It has been available since 1995 as a once-a-day medication and has been widely used to treat and prevent osteoporosis. Alendronate is marketed under the tradename Fosamaxâ.
Indications
Alendronate is used for the treatment or prevention of osteoporosis in postmenopausal women.
Dosage
The dose of alendronate for the treatment of osteoporosis is 70 mg once weekly. For prevention, the dose is 35 mg once weekly. It should be taken upon arising with plain water (6-8 oz) at least one-half hour before the first food, beverage, or medication of the day. The patient should not lie down for at least 30 minutes and until after their first food of the day.1 Patients should also receive supplemental calcium and vitamin D if these are not adequately supplied by the diet. Patients should be advised not to chew or suck on the tablets as this may cause oropharyngeal ulceration. If a dose is missed, patients should be advised to take it the next morning after they remember and return to the originally chosen weekly schedule. Alendronate is not recommended for patients with renal impairment (creatinine clearance < 35 mL/min).1
Potential Advantages
Once-weekly dosing may be more convenient as adherence to the strict dosing instructions need to be followed only once weekly instead of daily. Once-weekly dosing also reduces the esophageal exposure to the drug.
A trend toward a lower incidence of esophageal or gastric duodenal irritation was seen with the weekly dosing compared to daily dosing.2
Potential Disadvantages
Alendronate must be taken with specific instructions to reduce esophageal irritation. A retrospective database analysis reported that patients taking alendronate and who are elderly or are users of NSAIDs may have a greater risk of clinic visits and hospital admissions for acid-related gastrointestinal (GI) disorders.3
Comments
Alendronate inhibits the rate and extent of bone resorption by inhibiting osteoclast activity. This is shown by a decrease in osteocalcin, bone-specific alkaline phosphatase, and urinary markers such as cross-linked N-telopeptides of type 1 collagen. The drug’s half life on bone surface is several weeks, and these pharmacodynamics allow for weekly dosing. In a comparative 1-year study, 70 mg once weekly showed the same efficacy as 10 mg daily. The mean increases in bone mineral density (BMD) in the lumbar spine in those who completed the trial were 5.1% (95% CI = 4.8-54%) and 5.4% (95% CI = 5.0-5.8%) for the weekly and daily dosing, respectively.1,2
Increases in BMD at the total hip, femoral neck, trochanter, and total body were also similar. Similarly in a 1-year prevention trial, alendronate 35 mg weekly and 5 mg daily produced a 2.9% (95% CI = 2.6-3.2) and 3.2% (95% CI = 2.9-3.5%) increase in BMD, respectively.1 Long-term studies on fracture rates have not been conducted with the weekly regimens. While complaints such as dyspepsia and abdominal pain have been associated with alendronate administration, the drug did not appear to be associated with serious upper GI events in patients with no recent history of GI events.4 The daily and weekly regimens are priced the same.
Clinical Implications
Alendronate 35 mg and 70 mg provide an alternative to the daily regimens for the prevention and treatment of osteoporosis. These may be preferred for patients who cannot tolerate the daily dose or cannot follow the strict dosing instructions. Weekly and daily regimens appear to be comparable in efficacy as shown by BMD studies.
References
1. Fosamax Product Information. Merck & Co., Inc. October 2000.
2. Schnitzer T, et al. Aging Clin Exp Res. 2000;12:1-12.
3. Ettinger B, et al. Am J Manag Care. 1998;4: 1377-1382.
4. Bauer DC, et al. Arch Intern Med. 2000;160:517-525.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.