Few medications can be taken only one time per week. That might begin to change for some people as the result of a Food and Drug Administration action announced by Merck & Co., Inc. Two new dosage strengths of Fosamax(R) (alendronate sodium) have been approved as 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.
Fosamax once-weekly regimen therapeutically equivalent to once-daily
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)(1), 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(1)
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 3 to 4 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).
Vidyya has the full prescribing information for Fosamax for you.
(1) Completers analysis includes all patients who have baseline and
12-month endpoint data; intention-to-treat analysis includes all patients who
entered the study.