Actonel (RISEDRONATE) is a drug to treat and prevent osteoporosis. ACTONEL can reverse bone loss and help reduce the risk of fractures by stopping further loss of bone and increasing bone mass. ACTONEL is not a hormone like estrogen (hormone replacement therapy used in postmenopausal women). Therefore, it does not have all the benefits and risks of estrogen.

FACTS ABOUT ACTONEL

Actonel 35 mg Once-a-Week and Actonel 5 mg daily are approved by the United States Food and Drug Administration (FDA) for the treatment and prevention of osteoporosis in postmenopausal women. Actonel 5 mg also is indicated for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in women and men either initiating or continuing oral glucocorticoid steroid treatment (>7.5 mg/d prednisone or equivalent) for chronic diseases.
Clinical studies in women with postmenopausal osteoporosis and GIO have shown that Actonel 5 mg daily consistently reduces the incidence of vertebral (spinal) fractures in just one year.
Actonel 5 mg daily has also been shown to provide vertebral and nonvertebral fracture protection over five years. Nonvertebral fractures were measured as a composite endpoint of wrist, hip, pelvis, clavicle (collarbone), leg and humerus (upper arm).
Actonel 5 mg daily is the only osteoporosis therapy approved by the FDA for both treatment and prevention of GIO.
Actonel is in a class of drugs known as bisphosphonates.

Side Effects:
Most people have no problems with ACTONEL. However, ACTONEL may cause side effects. Side effects from ACTONEL are usually mild. They generally do not cause patients to stop taking ACTONEL. They include upset stomach, abdominal (stomach area) pain, constipation, diarrhea, gas, and headache.
Tell your health care provider if you feel discomfort in your stomach or esophagus (the tube connecting the mouth and the stomach). Stop taking ACTONEL and tell your health care provider right away if swallowing is difficult or painful, if you have chest pain, or if you have severe or continuing heartburn.

Contraindications (those who shouldn't take ACTONEL)
patients who have:
low blood calcium (hypocalcemia)
the inability to sit or stand upright for 30 minutes
an allergy to ACTONEL
severe kidney disease

Instructions for taking ACTONEL:
Take ACTONEL once daily or as directed by your health care provider. It is important to take ACTONEL as recommended so that you can benefit from the medicine. Following these recommendations also helps ACTONEL work correctly and helps you avoid possible irritation of the esophagus, the tube connecting the mouth and the stomach.

Take one ACTONEL tablet first thing in the morning while in an upright position (sitting or standing) before you have anything to eat or drink (other than plain water). Swallow ACTONEL whole rather than chewing it or waiting for it to dissolve. Do not eat or drink anything except plain water for 30 minutes after taking ACTONEL. After taking ACTONEL, wait at least 30 minutes before lying down. You may sit, stand, or do normal activities like read the newspaper, take a walk, etc.

Foods and some supplements and medicines can stop your body from absorbing ACTONEL. Therefore, do not take these products at or near the time you take ACTONEL: food, milk, calcium supplements, or calcium-, aluminum-, or magnesium-containing medicines, such as antacids. Ask your health care provider if there is anything else you should avoid while taking this medicine.

BENEFITS OF OSTEOPOROSIS TREATMENT ON FRACTURE RISK MAY BE GREAT, EVEN WHEN IMPROVEMENT IN BONE DENSITY IS SMALL

ORLANDO, FLORIDA—A recent study revealed that reduction in fracture risk from risedronate, a bisphosphonate medication commonly used to treat patients who have osteoporosis, is seen even in patients who have only small improvements in bone mass as measured by bone density, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Orlando, Florida.

Researchers reanalyzed data from the HIP and VERT studies of risedronate, which included nearly 9,000 patients from two randomized, double-blind clinical trials. Patients were selected to receive risedronate or placebo based on low bone mineral density (an indicator of bone strength) and/or pre-existing vertebral fracture. All patients also received daily supplements of calcium and vitamin D if baseline levels were low. Researchers examined the relationship between new vertebral fractures and changes in lumbar spine bone mineral density in both the placebo and risedronate groups. The results confirm that increases in bone mineral density results in a reduction in patients’ risk for fracture as compared to those whose bone mineral density decreases. Patients taking risedronate had a decreased risk of fracture compared to those taking placebo. Further, the results show that there was a significant reduction in fracture risk in all patients who had improvements in bone density, and that the reduction in fracture risk was independent of the magnitude of the improvement. Comparisons of bone mineral density increases among different therapies may not translate into meaningful differences in reducing fracture risk.

Fracture is a leading cause of disability in patients with osteoporosis, which affects 10 million people in the U.S., the majority of whom are women.

“Bone density measurements have helped us identify those who are at high risk for fractures,” said Jonathan Adachi, MD, Professor and Director of the Arthritis Centre at St. Joseph’s Hospital-McMaster University in Hamilton, Ontario, Canada, an investigator on the study. “In following patients on therapy, our study suggests that even moderate increases in bone density offer treatment benefit that is not significantly different from larger increases. This suggests that there may be a threshold above which further increases in bone density have little effect on fracture benefit. This also reinforces the need for further research to determine how osteoporosis therapies influence other elements of bone quality that affect the risk of fracture, such as bone turnover and bone micro-architecture.”

MINNEAPOLIS (September 22, 2003) – Actonel® (risedronate sodium tablets) helped preserve important aspects of bone quality at five years in postmenopausal women with osteoporosis, according to new research presented at the 25th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR).

"Studies suggest that bone quality may be an important contributor to bone strength and fracture resistance. These new data provide value in learning how therapies such as risedronate affect bone quality," said principal investigator Eleftherios P. Paschalis, PhD, Ludwig Boltzmann Institute for Osteology, Vienna. "However, additional studies are necessary to fully understand how the different aspects of bone quality relate to fracture risk."

One aspect of bone quality is the integrity of the material components of bone. Bone is a living tissue composed of calcium-based mineral crystals that are embedded in a network of protein fibers, called collagen. In osteoporotic bone, the calcium-based mineral crystals enlarge and the integrity of the collagen deteriorates compared to what is found in normal bone. Actonel, as shown in study biopsies, maintained the size of the calcium crystals and the integrity of the collagen structure over five years of treatment. Actonel is the only osteoporosis therapy for which these aspects of bone quality have been evaluated in bone biopsies taken from the same patients before and after five years of treatment.

About the Study
The study analyzed paired iliac crest biopsies from eight postmenopausal women with osteoporosis who received Actonel (5mg/day) over a 5-year period. The biopsies were analyzed with a novel imaging technique called Fourier Transform Infrared Spectroscopic Imaging (FTIRI), which provides microscopic information on the size of the calcium-based mineral crystals (crystallinity) and the structure of the collagen (collagen cross-link ratio, pyr/deH-DHLNL).

Biopsies were taken at baseline and at three years in 19 post-menopausal women who received either Actonel or placebo. In subjects treated for three years with placebo (n=8) there were statistically significant increases in both the mineral crystallinity (0.92 +/-06 at baseline vs. 1.22 +/- 0.04 at three years) and collagen cross-link ratio (1.40 +/- 0.20 at baseline vs. 1.90 +/- 0.04 at three years). In contrast, these parameters did not significantly change in the patients treated for three years with Actonel (n=11). Crystallinity before and after three years of treatment was 1.00 +/- 0.11 and 0.93 +/- 0.06, respectively. Collagen cross-link ratio before and after treatment was 1.61 +/- 0.40 and 1.61 +/- 0.86, respectively.

Eight of the Actonel patients had an additional biopsy performed after five years of treatment, and again the two bone quality parameters of crystallinity and collagen cross-link ratio had not changed from baseline. The crystallinity measurements before and after five years of treatment were 1.00 +/- 0.11 and 0.93 +/- 0.04, respectively. The collagen cross-link ratios before and after treatment were 1.61 +/- 0.40 and 1.64 +/- 0.52, respectively.

About Osteoporosis
Osteoporosis is a disease characterized by reduced bone strength predisposing a person to an increased risk of fracture. According to the National Osteoporosis Foundation (NOF), 8 million women in the U.S. have osteoporosis, and 1.2 million osteoporotic fractures occur annually. The NOF estimates that every 20 seconds an osteoporosis-related fracture occurs. Risk factors for osteoporosis in postmenopausal women include age, personal history or family history of fracture, low bone mineral density, cigarette use, and race.

Studies show that among postmenopausal women with osteoporosis who experience a spinal fracture, one out of five will suffer their next spinal fracture within just one year, potentially leading to a fracture cascade. Fractures can progress quickly if osteoporosis is left untreated. The NOF, National Institutes of Health, and American Association of Clinical Endocrinologists agree that fracture risk reduction is the efficacy endpoint by which osteoporosis therapies should be evaluated.

Preventive measures, such as not smoking, maintaining a balanced diet supplemented with calcium and vitamin D, if needed, and engaging in weight-bearing exercise, like walking, can reduce an individual's chances of developing osteoporosis. However, in some women, these preventive measures may not be enough, and prescription medications such as Actonel may be beneficial.

In clinical trials, Actonel was generally well tolerated. Actonel is contraindicated in patients with hypocalcemia, known hypersensitivity to any component of this product, or inability to stand or sit upright for at least 30 minutes. Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Actonel therapy. Actonel is not recommended for use in patients with severe renal impairment (creatinine clearance < 30 mL/min).

Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, esophagitis and esophageal or gastric ulcer. Patients should pay particular attention to the dosing instructions, as failure to take the drug according to instructions may compromise clinical benefits and may increase the risk of adverse events.

In clinical trials, the overall incidence of adverse events with Actonel 5 mg daily was comparable to placebo. The most commonly reported adverse events regardless of causality were infection (primarily upper respiratory, placebo 29.7 percent vs. Actonel 5 mg 29.9 percent), back pain (23.6 percent vs. 26.1 percent), and arthralgia (21.1 percent vs. 23.7 percent).

In a one-year clinical trial comparing Actonel 35 mg Once-a-Week and Actonel 5 mg daily, the overall incidence of adverse events with the two dosing regimens was similar. The most commonly reported adverse events regardless of causality were infection (Actonel 35 mg 20.6 percent vs. Actonel 5 mg 19.0 percent), arthralgia (14.2 percent vs. 11.5 percent) and constipation (12.2 percent vs. 12.5 percent). Please visit www.actonel.com for full prescribing information for Actonel.

¹ Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized, controlled trial. JAMA. 1999;282(14):1344-1352.

² Watts N, Roux C, Genant H, et al. Risedronate reduces vertebral fracture risk after the first year of treatment in postmenopausal women with established osteoporosis (abstract). J Bone Miner Res. 1999;14 (suppl 1):S136.

³ Wallach S, Cohen S, Reid DM, et al. Effects of risedronate therapy on bone density and vertebral fracture in patients on corticosteroid therapy. Calcified Tiss Int. 2000;67:277-285

⁴ Heaney RP, Zizic TM, Fogelman I, et al. Risedronate reduces the risk of first vertebral fracture in osteoporotic women. Osteoporosis Int 2002; 13: 501-505.

⁵ Data on file, Procter & Gamble Pharmaceuticals, Cincinnati, Ohio.

Young People Get Osteoporosis Too

Aventis Pharma United States - Actonel Factsheet

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