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

DECEMBER 01, 2008
Caryn Domenici, RPh, Alka Patel, PharmD, and Kevin Sullivan

Both Ms. Domenici and Dr. Patel are pharmacists at Brigham and Women's Hospital, Boston, Mass. Mr. Sullivan is a sixth-year PharmD candidate from Northeastern University School of Pharmacy currently on clinical clerkship in the Investigational Drug Service at Brigham and Women?s Hospital.

Procter & Gamble's and sanofi-aventis' Actonel

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

The new approval was based on a trial comparing risedronate 150 mg once a month with risedronate 5 mg daily. Actonel treatment at oncedaily, once-weekly, and 2 consecutive days per month has shown to be effective in postmenopausal women with osteoporosis. Treatment with Actonel slows the increased rate of bone turnover that is usually seen in postmenopausal women.3


Actonel acts as an antiresorptive agent due to its affinity for hydroxyapatite crystals. Actonel inhibits osteoclasts at the cellular level where the osteoclasts adhere normally to the bone surface, but there is reduced active resorption.3

Actonel is excreted primarily unchanged via the kidneys, and clearance of the drug decreases with decreasing kidney function. Actonel is not recommended for those with severe renal impairment (creatinine clearance [CrCl] <30 mL/min); however, no dosage adjustment is necessary for those with a CrCl of ≥30 mL/min.3

Clinical Trial

A randomized, double-blind, active-controlled, parallel-group study was conducted comparing risedronate 150 mg once a month (n = 650) with risedronate 5 mg daily (n = 642) for the treatment of postmenopausal osteoporosis.3 The study was conducted over 2 years; however, data for the second year are still being evaluated,4 according to the manufacturer (telephone interview July 2008). The study enrolled women aged 50 or older with postmenopausal osteoporosis. Postmenopausal was defined as last menses at least 5 years prior.

The primary efficacy end point was the mean percent change from baseline in lumbar spine bone mineral density after 1 year, which was 3.4% (3.03%-3.82%) in the daily group and 3.5% (3.15%-3.93%) in the once-a-month group. Increase in bone mineral density from baseline at sites in the hip (total proximal femur, femoral neck, femoral trochanter) was seen in both groups, with no significant difference observed between the 2 groups. The 150-mg dose was found to be noninferior to the 5-mg dose.

The adverse-events profile was similar between the 2 treatment arms.4 Among the most common adverse events, diarrhea (8.2% vs. 4.7%) and influenza (8.9% vs. 4.2%) occurred more frequently in the once-monthly group, compared with the daily group, respectively. Symptoms potentially associated with an acute phase reaction (influenza-like illness and/or pyrexia starting within 3 days following the first dose and having duration of 7 days or less), were slightly higher in the once-monthly group (1.4%) than in the once-daily group (0.2%).4 Of note, there were no reported cases of osteonecrosis of the jaw.3


It is important to note that the primary population in this study is postmenopausal women, and these results do not necessarily apply to the other populations for which Actonel once daily has been approved. This is why oncea- month Actonel is approved only for postmenopausal women.

Actonel is effective when administered 30 minutes prior to breakfast.3 Actonel 150 mg once a month produces clinical effects that are similar to those seen with a 5-mg daily dose regimen. It is different than currently available once-monthly osteoporosis medications in that it not only helps prevent fractures in the spine, but also at sites beyond the spine. Patients should be advised to take Actonel while the patient is in an upright position and with a full glass of plain water (6-8 oz). Patients should not lie down for 30 minutes after taking Actonel.


  1. FDA approves new once-a-month dose of Actonel for postmenopausal osteoporosis [press release]. www.sanofi-aventis.us.
  2. FDA. Actonel [consumer drug information sheet]. www.fda.gov/CDER/consumerinfo/druginfo/actonel.htm
  3. Actonel [package insert]. Cincinnati, OH and Bridgewater, NJ: Procter & Gamble Pharmaceuticals Inc and sanof-aventis US LLC; 2008.
  4. 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.