Pharmacology Update

Risedronate (Actonel)—A New Weekly Option for Osteoporosis

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

Risedronate has been approved in a 35 mg once weekly formulation for the treatment of osteoporosis. The drug is currently available as a 5 mg once daily product, but because the drug requires special precautions when it is taken, the once-a-week form may be more convenient. Alendronate (Fosamax), the other currently available oral bisphosphonate, is also available in a once a day and once a week formulation. Risedronate is marketed as Actonel by Proctor & Gamble and Aventis Pharmaceuticals.

Indications

Risedronate is indicated for the treatment and prevention of osteoporosis in postmenopausal women.

Dosage

Risedronate 35 mg is taken once weekly. It should be taken 30 minutes before the first food or drink of the day other than water. The patient should swallow the tablet with a full glass (6-8 oz) of water while in an upright position. The patient should not lie down for 30 minutes after taking the drug. Calcium, aluminum, or magnesium containing products should not be taken at the same time.1

Calcium and vitamin D supplementation is recommended in patients whose dietary intake is inadequate.

Risedronate is supplied as a 35-mg tablet for once-weekly dosing.

Potential Advantages

Risedronate may have better gastrointestinal (GI) tolerance than alendronate.2,3 Patients who have not tolerated alendronate because of upper GI side effects may tolerate risedronate. In a small, randomized, double-blind study (n = 66) patients who have discontinued alendronate due to upper GI side effects were given risedronate (5 mg daily) or placebo. Discontinuation due to upper GI side effects and the incidence of upper GI events in patients were comparable.4 A pooled analysis of 9 clinical trials concluded that risedronate 5 mg daily was not associated with a greater frequency of adverse GI events compared to placebo even among patients at high risk.5 The newly approved strength of risedronate permits once-weekly dosing and may reduce esophageal exposure.

Potential Disadvantages

The oral bioavailability of risedronate and bisphosphonates in general is low (about 1-3%). In addition, bioavailability is reduced by food, cations (such as calcium, aluminum, and magnesium), and liquids other than water. The most common side effects are mild-to-moderate GI events. To reduce upper GI side effects and reduce drug cation interaction, risedronate should be taken at least 30 minutes before the first food or drink. In addition, the patients should not lie down for 30 minutes after taking the drug. Products containing calcium, aluminum, or magnesium cations should be taken at a different time of the day.1

Comments

Risedronate is a pyridinyl bisphosphate recently approved for once-weekly dosing. The new dose (35 mg) was shown to be equivalent to 5 mg per day in terms of the increase on bone mineral density in lumbar spine after 1 year.1 The efficacy of daily administered risedronate for the treatment of postmenopausal osteoporosis in women has been established in large studies in Europe, Australia, and North America.1,6,7 It was also shown to be effective in increasing bone mineral density as preventive treatment of osteoporosis.8 The antifracture efficacy is considered to be comparable to alendronate.9 Alendronate and risedronate both reduce the risk of vertebral and nonvertebral fractures. The wholesale cost for risedronate 35 mg is about $52 for 4 weeks compared to about $55 for alendronate 70 mg for 4 weeks.

Clinical Implications

Bisphosphonates are effective in reducing the risk of vertebral and nonvertebral fractures but do not have any extra skeletal benefits. These drugs may be preferred in patients at high risk of nonvertebral fractures. Once-weekly risedronate provides another convenient alternative to alendronate and may be better tolerated in those who have not tolerated alendronate. 

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Actonel Product Information. Proctor & Gamble Pharmaceutical, Inc. May 2002.

2. Graham DY. Dig Dis Sci. 2002;47(8):1665-1678.

3. Baker DE. Rev Gastroenterol Disord. 2002;2(1):20-33.

4. Adachi JD, et al. Aging. (Milano) 2001;13(5):347-354.

5. Taggart H, et al. Mayo Clin Proc. 2002;77(3):262-270.

6. Reginster J, et al. Osteoporos Int. 2000;11(1):83-91.

7. Harris ST, et al. JAMA. 1999;282:1344-1352.

8. Mortensen L, et al. J Clin Endocrinol Metab. 1998;83: 396-402.

9. Delmas PD. Lancet. 2002;359:2018-2026.