Brand Name Drug: Actonel
Active Ingredient Drug: risedronate sodium
Indication: Treatment and prevention of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis (also approved for Paget’s disease of the bone in March 1998).
Company Name: Procter & Gamble; to be co-marketed with Aventis Pharmaceuticals
Availability: Approved by the FDA on April 17, 2000
Actonel (risedronate disodium) was approved in 1998 for the treatment of Paget’s disease. Now the drug, manufactured by Procter & Gamble and co-marketed with Aventis Pharmaceuticals, has received approval from the FDA (in April 2000) for the treatment and prevention of postmenopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIO).
Unlike other drugs for osteoporosis, Actonel is the first therapy that has consistently shown that its use can reduce vertebral fracture incidence in just one year of treatment – a significant finding, considering that nearly 20% of untreated osteoporosis patients who experience a vertebral fracture will fracture again within the following year. Approximately one in six patients initiating glucocorticoid therapy will suffer a vertebral fracture within one year, and up to 50% of patients on chronic glucocorticoid therapy will suffer a fracture. The recommended dosage of Actonel for both forms of osteoporosis is one 5 mg tablet once daily.
How It Works
Actonel belongs to the biphosphonate family of drugs. Actonel (risedronate disodium) has an affinity for hydroxyapatite crystals in bone and acts as an antiresorptive agent. At the cellular level, Actonel inhibits osteoclasts. The osteoclasts adhere normally to the bone surface, but show evidence of reduced active resorption (e.g., lack of ruffled border). Histomorphometry in rats, dogs, and minipigs showed that Actonel treatment reduces bone turnover (activation frequency, i.e., the rate at which bone remodeling sites are activated) and bone resorption at remodeling sites.
Actonel (risedronate disodium): Clinical Study Results
The efficacy of Actonel 5 mg daily was demonstrated in large, randomized, placebo-controlled, double-blind studies which enrolled a total of nearly 4,000 postmenopausal women. All patients received supplemental calcium and some also received supplemental vitamin D. Overall, Actonel significantly reduced the risk of new vertebral fractures by 65% in one year in postmenopausal women compared to a control group of women taking supplemental calcium and, if needed, vitamin D (6.4% of patients in the control group vs. 2.4% of patients taking Actonel fractured). In high-risk patients (those with two or more previous vertebral fractures), Actonel significantly reduced the risk of vertebral fractures by up to 74% in just one year (9.8% of patients in the control group vs. 2.7% of patients taking Actonel fractured). Reductions of vertebral fracture risk were seen throughout the 3-year study duration.
There was a significant reduction from 11% to 7% in the incidence of nonvertebral fractures as well, with a corresponding 36% reduction in relative risk. Actonel also increased bone mineral density (BMD) at the spine, hip, and wrist – particularly the lumbar spine, femoral neck, femoral trochanter, and midshaft radius – compared to the effects seen with placebo, and was associated with less loss of height than placebo, both in women with a history of vertebral fractures as well as those with no fractures but low lumbar spine bone mass. Bone biopsies from 110 women taking Actonel (risedronate disodium) showed that bone formation was of normal quality.
Actonel 5 mg daily prevented bone loss in a majority of postmenopausal women within 3 years of menopause in a 2-year, double-blind, placebo-controlled study in 383 patients. All patients in this study received supplemental calcium 1000 mg/day. Increases in BMD were observed as early as 3 months following initiation of Actonel treatment. Actonel 5 mg produced significant mean increases in BMD at the lumbar spine, femoral neck, and trochanter compared to placebo at the end of the study. Actonel 5 mg daily was also effective in patients with lower baseline lumbar spine BMD and in those with normal baseline lumbar spine BMD. BMD at the distal radius decreased in both Actonel and placebo-treated women following 1 year of treatment.
Two 1-year, double-blind, placebo-controlled trials in patients who were taking at least 7.5 mg/day of prednisone or equivalent demonstrated that Actonel 5 mg once daily was effective in the prevention and treatment of glucocorticoid-induced osteoporosis in men and women either initiating or continuing glucocorticoid therapy. Combined results from the studies demonstrated that treatment with Actonel for 1 year significantly reduced vertebral fractures by 70% (16.2% of patients in the control group vs. 5.4% of patients taking Actonel fractured). Actonel was also shown to maintain or increase BMD in studies of more than 500 patients: By the third month of treatment, and continuing through the year-long treatment, the placebo group experienced losses in BMD at the lumbar spine, femoral neck, and trochanter, while BMD was maintained or increased in the Actonel group. Bone biopsies from 40 patients taking Actonel showed that bone formation was of normal quality.
What the Patient Should Know
Bisphosphonates may cause upper gastrointestinal disorders, such as dysphagia, esophagitis, and esophageal or gastric ulcers. Nevertheless, Actonel is generally well-tolerated, even in patients with gastrointestinal disease. The incidence of side effects was similar to that of placebo. Most side effects were mild to moderate and did not require patients to stop taking Actonel. Other side effects included infection (primarily upper respiratory) and back and joint pain.
Patients should take Actonel (risedronate disodium) with a full glass of plain water (6-8 oz.) to facilitate delivery to the stomach, and should not lie down for 30 minutes after taking the drug. They should be instructed that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain, or severe persistent or worsening heartburn) they should consult their physician before continuing Actonel.
Actonel should not be used in patients with low blood calcium, known allergy to Actonel, or an inability to stand or sit upright for at least 30 minutes. Low blood calcium and other disturbances of bone and mineral metabolism should be effectively treated before starting Actonel therapy. Actonel (risedronate disodium) is not recommended for use in patients with severe kidney disease.