Rx Product News: Profile: A Closer Look at New FDA Actions: Actonel

Both Ms. Domenici and Dr. Patel arepharmacists at Brigham and Women'sHospital, Boston, Mass. Mr. Sullivanis a sixth-year PharmD candidatefrom Northeastern University School ofPharmacy currently on clinical clerkshipin the Investigational Drug Service atBrigham and Women?s Hospital.

Procter & Gamble's andsanofi-aventis' Actonel

On April 22, 2008, the FDA approvedthe use of Actonel (risedronate sodium)150-mg tablets as a once-monthly doseto treat and prevent postmenopausalosteoporosis.¹ Actonel's original 1998approval was for the treatment andprevention of postmenopausal osteoporosis,men with osteoporosis, glucocorticoid-induced osteoporosis, andPaget's disease.²

The new approval was based ona trial comparing risedronate 150mg once a month with risedronate 5mg daily. Actonel treatment at oncedaily,once-weekly, and 2 consecutivedays per month has shown to beeffective in postmenopausal womenwith osteoporosis. Treatment withActonel slows the increased rate ofbone turnover that is usually seen inpostmenopausal women.³

Pharmacology/Pharmacokinetics

Actonel acts as an antiresorptive agentdue to its affinity for hydroxyapatitecrystals. Actonel inhibits osteoclasts atthe cellular level where the osteoclastsadhere normally to the bone surface,but there is reduced active resorption.³

Actonel is excreted primarily unchangedvia the kidneys, and clearanceof the drug decreases with decreasingkidney function. Actonel is not recommendedfor those with severe renalimpairment (creatinine clearance [CrCl]<30 mL/min); however, no dosageadjustment is necessary for those witha CrCl of ≥30 mL/min.³

Clinical Trial

A randomized, double-blind, active-controlled,parallel-group study was conductedcomparing risedronate 150 mgonce a month (n = 650) with risedronate5 mg daily (n = 642) for the treatmentof postmenopausal osteoporosis.³The study was conducted over 2 years;however, data for the second year arestill being evaluated,⁴ according to themanufacturer (telephone interview July2008). The study enrolled women aged50 or older with postmenopausal osteoporosis.Postmenopausal was definedas last menses at least 5 years prior.

The primary efficacy end pointwas the mean percent change frombaseline in lumbar spine bone mineraldensity after 1 year, which was 3.4%(3.03%-3.82%) in the daily group and3.5% (3.15%-3.93%) in the once-a-monthgroup. Increase in bone mineral densityfrom baseline at sites in the hip (totalproximal femur, femoral neck, femoraltrochanter) was seen in both groups,with no significant difference observedbetween the 2 groups. The 150-mg dosewas found to be noninferior to the 5-mgdose.

The adverse-events profile was similarbetween the 2 treatment arms.⁴Among the most common adverseevents, diarrhea (8.2% vs. 4.7%) andinfluenza (8.9% vs. 4.2%) occurred morefrequently in the once-monthly group,compared with the daily group, respectively.Symptoms potentially associatedwith an acute phase reaction (influenza-like illness and/or pyrexia startingwithin 3 days following the first doseand having duration of 7 days or less),were slightly higher in the once-monthlygroup (1.4%) than in the once-dailygroup (0.2%).⁴ Of note, there were noreported cases of osteonecrosis of thejaw.³

Conclusion

It is important to note that theprimary population in this studyis postmenopausal women, andthese results do not necessarilyapply to the other populationsfor which Actonel once daily hasbeen approved. This is why oncea-month Actonel is approved onlyfor postmenopausal women.

Actonel is effective when administered30 minutes prior to breakfast.³Actonel 150 mg once a month producesclinical effects that are similar to thoseseen with a 5-mg daily dose regimen.It is different than currently availableonce-monthly osteoporosis medicationsin that it not only helps prevent fracturesin the spine, but also at sites beyond thespine. Patients should be advised totake Actonel while the patient is in anupright position and with a full glassof plain water (6-8 oz). Patients shouldnot lie down for 30 minutes after takingActonel.

References

• FDA approves new once-a-month dose of Actonel for postmenopausal osteoporosis [press release]. www.sanofi-aventis.us.
• FDA. Actonel [consumer drug information sheet]. www.fda.gov/CDER/consumerinfo/druginfo/actonel.htm
• Actonel [package insert]. Cincinnati, OH and Bridgewater, NJ: Procter & Gamble Pharmaceuticals Inc and sanof-aventis US LLC; 2008.
• Delmas PD, McClung MR, Zanchetta JR, et al. Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis. Bone. 2008;42(1):36-42.