And It's About Time There Was Some Support For Cushing's!
WEST POINT, PA -- October 24, 2000 -- The Food and Drug Administration (FDA) has approved two new dosage strengths of Merck & Co., Inc.'s Fosamax® (alendronate sodium), once-weekly tablets -- 70 mg for the treatment of postmenopausal osteoporosis and 35 mg for the prevention of postmenopausal osteoporosis.
Fosamax is the first and only oral medication approved for the treatment and prevention of postmenopausal osteoporosis in a once-weekly dosing regimen.
"For the millions of postmenopausal women who currently have osteoporosis or are at risk for the disease, the FDA's decision to approve Fosamax in a once-weekly dose marks an important development in the treatment and prevention of osteoporosis," said Thomas J. Schnitzer, M.D., Ph.D., professor and director, Office of Clinical Research and Training, Northwestern University. "Patients and their health care professionals now have the opportunity to choose between once-daily and once-weekly Fosamax, and the once-weekly regimen may be more convenient for some patients."
In addition to the new once-weekly dosages in the 70 mg and 35 mg strengths, Fosamax continues to be available in once-daily dosages for the treatment (10 mg) and prevention (5 mg) of postmenopausal osteoporosis.
The approval of Fosamax in a dosage form containing seven times the daily dosage strength was based on a clinical study that showed Fosamax 70 mg taken once a week had equivalent effect to Fosamax 10 mg taken once a day in increasing bone mineral density (BMD) in postmenopausal women.
In a one-year, double-blind, multicenter study involving postmenopausal women with osteoporosis, women were randomized to either Fosamax 70 mg once weekly (n=519) or Fosamax 10 mg once daily (n=370). In the primary analysis of completers (n=770), the mean increases from baseline in lumbar spine BMD at the end of one year were therapeutically equivalent: 5.1 percent in the Fosamax 70 mg once-weekly group and 5.4 percent in the Fosamax 10 mg once- daily group. Increases in BMD at the hip and total body were also similar in the two treatment groups. The results of the intention-to-treat analysis were consistent with the primary analysis of completers. To ensure adequate calcium and vitamin D intake, all patients in the study received calcium and vitamin D supplements.
In the clinical trial, the safety and tolerability profiles of Fosamax 70 mg once weekly and the 10 mg once daily regimen were similar. The most common gastrointestinal (GI) adverse experiences were abdominal pain, indigestion, acid regurgitation and nausea. There were no statistically significant differences between the two dosing regimens in upper GI adverse experiences that resulted in discontinuation from the study.
An additional analysis showed that there was no significant increase in the incidence of upper GI adverse events observed on the day of dosing between patients receiving Fosamax 70 mg once weekly and those receiving Fosamax 10 mg once daily.
To assist patients in following the dosing regimen for the once-weekly dosing of Fosamax, a patient-friendly blister package containing a four-week supply has been developed. Patients can select a day of the week that works best for them to take the once-weekly dose of Fosamax. If a dose of Fosamax once weekly is missed, patients should take that tablet the morning after it is remembered. Patients should not take two tablets on the same day, but should return to taking one tablet once a week as originally scheduled on their chosen day.
Apart from the dosing frequency, the dosing administration instructions for the once-weekly and once-daily formulations are the same. To facilitate delivery to the stomach and thus reduce the potential for esophageal irritation, patients must take Fosamax upon arising for the day with a full glass of plain water (six to eight ounces). After swallowing Fosamax, patients must not lie down and should stay fully upright (sitting or standing) for at least 30 minutes and until after the first food of the day. Fosamax should not be taken at bedtime or before arising for the day. Patients should not chew or suck on the tablets.
Fosamax, like other bisphosphonates, should be used with caution in people with certain stomach or digestive problems. Fosamax should not be used if the patient has certain disorders of the esophagus that delay emptying or if the patient is unable to stand or sit upright for at least 30 minutes. In addition, Fosamax should not be used in patients with severe kidney disease or low levels of calcium in their blood, in patients who are allergic to Fosamax or in patients who are pregnant or nursing.
Some patients may develop severe digestive reactions including irritation, inflammation or ulceration of the esophagus. The risk of severe esophageal experiences appears to be greater in patients who fail to follow dosing instructions (see prescribing information for more details). Patients who experience heartburn, difficulty or pain when swallowing or chest pain should stop taking the drug and consult their doctor.
Fosamax now provides physicians and health care providers with the option to prescribe the once-weekly regimen at the same catalog price as a week's worth of the daily regimen. Merck's catalog price to all direct purchasers for the 70 mg once-weekly regimen is $49.39 for a four-week supply of tablets.
Prices at the retail level are independently established by individual pharmacies, not by Merck. Historically, retail markups have been approximately 15 percent to 25 percent. The new 70 mg tablet should be available in pharmacies in three to four weeks. The 35 mg tablet will be available in pharmacies in early 2001.
The FDA cleared Fosamax for marketing in 1995 for the treatment of postmenopausal osteoporosis (10 mg once daily) and for treatment of Paget's disease of bone (40 mg once daily). In 1997, Fosamax (5 mg once daily) was approved for the prevention of osteoporosis in postmenopausal women at risk of osteoporosis, and Fosamax (10 mg once daily) was approved for the reduction in incidence of fractures in postmenopausal women who have osteoporosis.
In June 1999, Fosamax was approved as the first medication for the treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids (commonly referred to as corticosteroids or steroids) in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low bone mineral density.
In September 2000, Fosamax became the first medicine approved for the treatment to increase bone mass in men with osteoporosis (10 mg once daily).