FOSAMAX1 (alendronate sodium) is a bisphosphonate that
acts as a specific inhibitor of osteoclast-mediated bone resorption.
Bisphosphonates are synthetic analogs of pyrophosphate that bind to the
hydroxyapatite found in bone.
Alendronate sodium is chemically described as (4-amino-1-hydroxybutylidene)
bisphosphonic acid monosodium salt trihydrate. The empirical formula of alendronate sodium is C4H12NNaO7P2•3H2O and its formula weight is 325.12.
The structural formula is:
Alendronate sodium is a white, crystalline, nonhygroscopic powder. It is
soluble in water, very slightly soluble in alcohol, and practically insoluble in
chloroform.
Tablets FOSAMAX for oral administration contain 6.53, 13.05, 45.68, 52.21 or
91.37 mg of alendronate monosodium salt trihydrate, which is the molar
equivalent of 5, 10, 35, 40 and 70 mg, respectively, of free acid, and the
following inactive ingredients: microcrystalline cellulose, anhydrous lactose,
croscarmellose sodium, and magnesium stearate. Tablets FOSAMAX 10 mg also
contain carnauba wax.
Mechanism of Action Animal studies have indicated the following mode of action. At
the cellular level, alendronate shows preferential localization to sites of bone
resorption, specifically under osteoclasts. The osteoclasts adhere normally to
the bone surface but lack the ruffled border that is indicative of active
resorption. Alendronate does not interfere with osteoclast recruitment or
attachment, but it does inhibit osteoclast activity. Studies in mice on the
localization of radioactive [3H]alendronate in bone
showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast
surfaces. Bones examined 6 and 49 days after [3H]alendronate administration in rats and mice, respectively,
showed that normal bone was formed on top of the alendronate, which was
incorporated inside the matrix. While incorporated in bone matrix, alendronate
is not pharmacologically active. Thus, alendronate must be continuously
administered to suppress osteoclasts on newly formed resorption surfaces.
Histomorphometry in baboons and rats showed that alendronate treatment reduces
bone turnover (i.e., the number of sites at which bone is remodeled). In
addition, bone formation exceeds bone resorption at these remodeling sites,
leading to progressive gains in bone mass. PharmacokineticsAbsorption Relative to an intravenous (IV) reference dose, the mean oral
bioavailability of alendronate in women was 0.64% for doses ranging from 5 to
70 mg when administered after an overnight fast and two hours before a
standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%)
was similar to that in women when administered after an overnight fast and
2 hours before breakfast.
FOSAMAX 70 mg oral solution and FOSAMAX 70 mg tablet are equally
bioavailable.
A study examining the effect of timing of a meal on the bioavailability of
alendronate was performed in 49 postmenopausal women. Bioavailability was
decreased (by approximately 40%) when 10 mg alendronate was administered either
0.5 or 1 hour before a standardized breakfast, when compared to dosing 2 hours
before eating. In studies of treatment and prevention of osteoporosis,
alendronate was effective when administered at least 30 minutes before
breakfast.
Bioavailability was negligible whether alendronate was administered with or
up to two hours after a standardized breakfast. Concomitant administration of
alendronate with coffee or orange juice reduced bioavailability by approximately
60%. Distribution Preclinical studies (in male rats) show that alendronate
transiently distributes to soft tissues following 1 mg/kg IV administration but
is then rapidly redistributed to bone or excreted in the urine. The mean
steady-state volume of distribution, exclusive of bone, is at least 28 L in
humans. Concentrations of drug in plasma following therapeutic oral doses are
too low (less than 5 ng/mL) for analytical detection. Protein binding in human
plasma is approximately 78%. Metabolism There is no evidence that alendronate is metabolized in animals
or humans. Excretion Following a single IV dose of [14C]alendronate, approximately 50% of the radioactivity was
excreted in the urine within 72 hours and little or no radioactivity was
recovered in the feces. Following a single 10 mg IV dose, the renal clearance of
alendronate was 71 mL/min (64, 78; 90% confidence interval [CI]), and systemic
clearance did not exceed 200 mL/min. Plasma concentrations fell by more than 95%
within 6 hours following IV administration. The terminal half-life in humans is
estimated to exceed 10 years, probably reflecting release of alendronate from
the skeleton. Based on the above, it is estimated that after 10 years of oral
treatment with FOSAMAX (10 mg daily) the amount of alendronate released daily
from the skeleton is approximately 25% of that absorbed from the
gastrointestinal tract. Special PopulationsPediatric: The oral bioavailability in children was similar to that observed
in adults; however, FOSAMAX is not indicated for use in children (see PRECAUTIONS, Pediatric Use). Gender: Bioavailability and the fraction of an IV dose excreted in urine
were similar in men and women. Geriatric: Bioavailability and disposition (urinary excretion) were similar
in elderly and younger patients. No dosage adjustment is necessary (see DOSAGE AND ADMINISTRATION). Race: Pharmacokinetic differences due to race have not been
studied. Renal Insufficiency: Preclinical studies show that, in rats with kidney failure,
increasing amounts of drug are present in plasma, kidney, spleen, and tibia. In
healthy controls, drug that is not deposited in bone is rapidly excreted in the
urine. No evidence of saturation of bone uptake was found after 3 weeks dosing
with cumulative IV doses of 35 mg/kg in young male rats. Although no clinical
information is available, it is likely that, as in animals, elimination of
alendronate via the kidney will be reduced in patients with impaired renal
function. Therefore, somewhat greater accumulation of alendronate in bone might
be expected in patients with impaired renal function.
No dosage adjustment is necessary for patients with mild-to-moderate renal
insufficiency (creatinine clearance 35 to 60 mL/min). FOSAMAX
is not recommended for patients with more severe renal insufficiency (creatinine
clearance less than 35 mL/min) due to lack of experience with alendronate in renal
failure. Hepatic Insufficiency: As there is evidence that alendronate is not metabolized or
excreted in the bile, no studies were conducted in patients with hepatic
insufficiency. No dosage adjustment is necessary. Drug Interactions (also see PRECAUTIONS, Drug
Interactions)
Intravenous ranitidine was shown to double the bioavailability of oral
alendronate. The clinical significance of this increased bioavailability and
whether similar increases will occur in patients given oral H2-antagonists is unknown.
In healthy subjects, oral prednisone (20 mg three times daily for five days)
did not produce a clinically meaningful change in the oral bioavailability of
alendronate (a mean increase ranging from 20 to 44%).
Products containing calcium and other multivalent cations are likely to
interfere with absorption of alendronate. Pharmacodynamics Alendronate is a bisphosphonate that binds to bone hydroxyapatite
and specifically inhibits the activity of osteoclasts, the bone-resorbing cells.
Alendronate reduces bone resorption with no direct effect on bone formation,
although the latter process is ultimately reduced because bone resorption and
formation are coupled during bone turnover. Osteoporosis in postmenopausal women Osteoporosis is characterized by low bone mass that leads to an
increased risk of fracture. The diagnosis can be confirmed by the finding of low
bone mass, evidence of fracture on x-ray, a history of osteoporotic fracture, or
height loss or kyphosis, indicative of vertebral (spinal) fracture. Osteoporosis
occurs in both males and females but is most common among women following the
menopause, when bone turnover increases and the rate of bone resorption exceeds
that of bone formation. These changes result in progressive bone loss and lead
to osteoporosis in a significant proportion of women over age 50. Fractures,
usually of the spine, hip, and wrist, are the common consequences. From age 50
to age 90, the risk of hip fracture in white women increases 50-fold and the
risk of vertebral fracture 15- to 30-fold. It is estimated that approximately
40% of 50-year-old women will sustain one or more osteoporosis-related fractures
of the spine, hip, or wrist during their remaining lifetimes. Hip fractures, in
particular, are associated with substantial morbidity, disability, and
mortality.
Daily oral doses of alendronate (5, 20, and 40 mg for six weeks) in
postmenopausal women produced biochemical changes indicative of dose-dependent
inhibition of bone resorption, including decreases in urinary calcium and
urinary markers of bone collagen degradation (such as deoxypyridinoline and
cross-linked N-telopeptides of type I collagen). These biochemical changes
tended to return toward baseline values as early as 3 weeks following the
discontinuation of therapy with alendronate and did not differ from placebo
after 7 months.
Long-term treatment of osteoporosis with FOSAMAX 10 mg/day (for up to five
years) reduced urinary excretion of markers of bone resorption,
deoxypyridinoline and cross-linked N-telopeptides of type l collagen, by
approximately 50% and 70%, respectively, to reach levels similar to those seen
in healthy premenopausal women. Similar decreases were seen in patients in
osteoporosis prevention studies who received FOSAMAX 5 mg/day. The decrease in
the rate of bone resorption indicated by these markers was evident as early as
one month and at three to six months reached a plateau that was maintained for
the entire duration of treatment with FOSAMAX. In osteoporosis treatment studies
FOSAMAX 10 mg/day decreased the markers of bone formation, osteocalcin and bone
specific alkaline phosphatase by approximately 50%, and total serum alkaline
phosphatase by approximately 25 to 30% to reach a plateau after 6 to 12 months.
In osteoporosis prevention studies FOSAMAX 5 mg/day decreased osteocalcin and
total serum alkaline phosphatase by approximately 40% and 15%, respectively.
Similar reductions in the rate of bone turnover were observed in postmenopausal
women during one-year studies with once weekly FOSAMAX 70 mg for the treatment
of osteoporosis and once weekly FOSAMAX 35 mg for the prevention of
osteoporosis. These data indicate that the rate of bone turnover reached a new
steady-state, despite the progressive increase in the total amount of
alendronate deposited within bone.
As a result of inhibition of bone resorption, asymptomatic reductions in
serum calcium and phosphate concentrations were also observed following
treatment with FOSAMAX. In the long-term studies, reductions from baseline in
serum calcium (approximately 2%) and phosphate (approximately 4 to 6%) were
evident the first month after the initiation of FOSAMAX 10 mg. No further
decreases in serum calcium were observed for the five-year duration of
treatment; however, serum phosphate returned toward prestudy levels during years
three through five. Similar reductions were observed with FOSAMAX 5 mg/day. In
one-year studies with once weekly FOSAMAX 35 and 70 mg, similar reductions were
observed at 6 and 12 months. The reduction in serum phosphate may reflect not
only the positive bone mineral balance due to FOSAMAX but also a decrease in
renal phosphate reabsorption. Osteoporosis in men Treatment of men with osteoporosis with FOSAMAX 10 mg/day for two
years reduced urinary excretion of cross-linked N-telopeptides of type I
collagen by approximately 60% and bone-specific alkaline phosphatase by
approximately 40%. Similar reductions were observed in a one-year study in men
with osteoporosis receiving once weekly FOSAMAX 70 mg. Glucocorticoid-induced Osteoporosis Sustained use of glucocorticoids is commonly associated with
development of osteoporosis and resulting fractures (especially vertebral, hip,
and rib). It occurs both in males and females of all ages. Osteoporosis occurs
as a result of inhibited bone formation and increased bone resorption resulting
in net bone loss. Alendronate decreases bone resorption without directly
inhibiting bone formation.
In clinical studies of up to two years' duration, FOSAMAX 5 and 10 mg/day
reduced cross-linked N-telopeptides of type I collagen (a marker of bone
resorption) by approximately 60% and reduced bone-specific alkaline phosphatase
and total serum alkaline phosphatase (markers of bone formation) by
approximately 15 to 30% and 8 to 18%, respectively. As a result of inhibition of
bone resorption, FOSAMAX 5 and 10 mg/day induced asymptomatic decreases in serum
calcium (approximately 1 to 2%) and serum phosphate (approximately 1
to 8%). Paget's disease of bone Paget's disease of bone is a chronic, focal skeletal disorder
characterized by greatly increased and disorderly bone remodeling. Excessive
osteoclastic bone resorption is followed by osteoblastic new bone formation,
leading to the replacement of the normal bone architecture by disorganized,
enlarged, and weakened bone structure.
Clinical manifestations of Paget's disease range from no symptoms to severe
morbidity due to bone pain, bone deformity, pathological fractures, and
neurological and other complications. Serum alkaline phosphatase, the most
frequently used biochemical index of disease activity, provides an objective
measure of disease severity and response to therapy.
FOSAMAX decreases the rate of bone resorption directly, which leads to an
indirect decrease in bone formation. In clinical trials, FOSAMAX 40 mg once
daily for six months produced significant decreases in serum alkaline
phosphatase as well as in urinary markers of bone collagen degradation. As a
result of the inhibition of bone resorption, FOSAMAX induced generally mild,
transient, and asymptomatic decreases in serum calcium and phosphate. Clinical StudiesTreatment of Osteoporosis Postmenopausal womenEffect on bone mineral density
The efficacy of FOSAMAX 10 mg once daily in postmenopausal women,
44 to 84 years of age, with osteoporosis (lumbar spine bone mineral density
[BMD] of at least 2 standard deviations below the premenopausal mean) was
demonstrated in four double-blind, placebo-controlled clinical studies of two or
three years' duration. These included two three-year, multicenter studies of
virtually identical design, one performed in the United States (U.S.) and the
other in 15 different countries (Multinational), which enrolled 478 and 516
patients, respectively. The following graph shows the mean increases in BMD of
the lumbar spine, femoral neck, and trochanter in patients receiving FOSAMAX
10 mg/day relative to placebo-treated patients at three years for each of these
studies.
Osteoporosis Treatment Studies in Postmenopausal
Women: Increase in BMD: FOSAMAX 10mg/day at Three Years
At three years significant increases in BMD, relative both to baseline and
placebo, were seen at each measurement site in each study in patients who
received FOSAMAX 10 mg/day. Total body BMD also increased significantly in each
study, suggesting that the increases in bone mass of the spine and hip did not
occur at the expense of other skeletal sites. Increases in BMD were evident as
early as three months and continued throughout the three years of treatment.
(See figures below for lumbar spine results.) In the two-year extension of these
studies, treatment of 147 patients with FOSAMAX 10 mg/day resulted in continued
increases in BMD at the lumbar spine and trochanter (absolute additional
increases between years 3 and 5: lumbar spine, 0.94%; trochanter, 0.88%). BMD at
the femoral neck, forearm and total body were maintained. FOSAMAX was similarly
effective regardless of age, race, baseline rate of bone turnover, and baseline
BMD in the range studied (at least 2 standard deviations below the premenopausal
mean). Thus, overall FOSAMAX reverses the loss of bone mineral density, a
central factor in the progression of osteoporosis.
Osteoporosis Treatment Studies in Postmenopausal
Women: Time Course of Effect of FOSAMAX 10 mg/day Versus Placebo: Lumbar Spine
BMD Percent Change From Baseline
In patients with postmenopausal osteoporosis treated with FOSAMAX 10 mg/day
for one or two years, the effects of treatment withdrawal were assessed.
Following discontinuation, there were no further increases in bone mass and the
rates of bone loss were similar to those of the placebo groups. These data
indicate that continued treatment with FOSAMAX is required to maintain the
effect of the drug.
The therapeutic equivalence of once weekly FOSAMAX 70 mg (n=519) and FOSAMAX
10 mg daily (n=370) was demonstrated in a one-year, double-blind, multicenter
study of postmenopausal women with osteoporosis. In the primary analysis of
completers, the mean increases from baseline in lumbar spine BMD at one year
were 5.1% (4.8, 5.4%; 95% CI) in the 70-mg once-weekly group (n=440) and 5.4%
(5.0, 5.8%; 95% CI) in the 10-mg daily group (n=330). The two treatment groups
were also similar with regard to BMD increases at other skeletal sites. The
results of the intention-to-treat analysis were consistent with the primary
analysis of completers.
Effect on fracture incidence Data on the effects of FOSAMAX on fracture incidence are derived
from three clinical studies: 1) U.S. and Multinational combined: a study of
patients with a BMD T-score at or below minus 2.5 with or without a prior
vertebral fracture, 2) Three-Year Study of the Fracture Intervention Trial
(FIT): a study of patients with at least one baseline vertebral fracture, and 3)
Four-Year Study of FIT: a study of patients with low bone mass but without a
baseline vertebral fracture.
To assess the effects of FOSAMAX on the incidence of vertebral fractures
(detected by digitized radiography; approximately one third of these were
clinically symptomatic), the U.S. and Multinational studies were combined in an
analysis that compared placebo to the pooled dosage groups of FOSAMAX
(5 or 10 mg for three years or 20 mg for two years followed by 5 mg for one
year). There was a statistically significant reduction in the proportion of
patients treated with FOSAMAX experiencing one or more new vertebral fractures
relative to those treated with placebo (3.2% vs. 6.2%; a 48% relative risk
reduction). A reduction in the total number of new vertebral fractures (4.2 vs.
11.3 per 100 patients) was also observed. In the pooled analysis, patients who
received FOSAMAX had a loss in stature that was statistically significantly less
than was observed in those who received placebo (-3.0 mm vs. -4.6 mm).
The Fracture Intervention Trial (FIT) consisted of two studies in
postmenopausal women: the Three-Year Study of patients who had at least one
baseline radiographic vertebral fracture and the Four-Year Study of patients
with low bone mass but without a baseline vertebral fracture. In both studies of
FIT, 96% of randomized patients completed the studies (i.e., had a closeout
visit at the scheduled end of the study); approximately 80% of patients were
still taking study medication upon completion. Fracture Intervention Trial: Three-Year Study
(patients with at least one baseline radiographic vertebral fracture) This randomized, double-blind, placebo-controlled, 2027-patient
study (FOSAMAX, n=1022; placebo, n=1005) demonstrated that treatment with
FOSAMAX resulted in statistically significant reductions in fracture incidence
at three years as shown in the table below.
Effect of FOSAMAX on Fracture Incidence in the Three-Year Study of FIT (patients with vertebral fracture at baseline)
FOSAMAX(n=1022)
Percent of Patients
Placebo(n=1005)
AbsoluteReductionin FractureIncidence
RelativeReduction inFractureRisk %
Patients with:Vertebral fractures (diagnosed by X-ray)*
≥ 1 new vertebral fracture
* Number evaluable for vertebral fractures: FOSAMAX, n=984; placebo, n=966
† p less than 0.001
‡ p=0.007
§ p less than 0.01
¶ p less than 0.05
Furthermore, in this population of patients with baseline vertebral fracture,
treatment with FOSAMAX significantly reduced the incidence of hospitalizations
(25.0% vs. 30.7%).
In the Three-Year Study of FIT, fractures of the hip occurred in 22 (2.2%) of
1005 patients on placebo and 11 (1.1%) of 1022 patients on FOSAMAX, p=0.047. The
figure below displays the cumulative incidence of hip fractures in this study.
Cumulative Incidence of Hip Fractures in the
Three-Year Study of FIT (patients with radiographic vertebral fracture at
baseline) Fracture Intervention Trial: Four-Year Study
(patients with low bone mass but without a baseline radiographic vertebral
fracture) This randomized, double-blind, placebo-controlled, 4432-patient
study (FOSAMAX, n=2214; placebo, n=2218) further investigated the reduction in
fracture incidence due to FOSAMAX. The intent of the study was to recruit women
with osteoporosis, defined as a baseline femoral neck BMD at least two standard
deviations below the mean for young adult women. However, due to subsequent
revisions to the normative values for femoral neck BMD, 31% of patients were
found not to meet this entry criterion and thus this study included both
osteoporotic and non-osteoporotic women. The results are shown in the table
below for the patients with osteoporosis.
Effect of FOSAMAX on Fracture Incidence in Osteoporotic* Patients in the Four-Year Study of FIT (patients without vertebral fracture at baseline)
* Baseline femoral neck BMD at least 2 SD below the mean for young adult women
† Number evaluable for vertebral fractures: FOSAMAX, n=1426; placebo, n=1428
‡ p less than 0.001
§ p=0.035
¶ p=0.01
# Not significant. This study was not powered to detect differences at these
sites.
Fracture results across studies In the Three-Year Study of FIT, FOSAMAX reduced the percentage of
women experiencing at least one new radiographic vertebral fracture from 15.0%
to 7.9% (47% relative risk reduction, p less than 0.001); in the Four-Year Study of
FIT, the percentage was reduced from 3.8% to 2.1% (44% relative risk reduction,
p=0.001); and in the combined U.S./Multinational studies, from 6.2% to 3.2% (48%
relative risk reduction, p=0.034).
FOSAMAX reduced the percentage of women experiencing multiple (two or more)
new vertebral fractures from 4.2% to 0.6% (87% relative risk reduction,
p less than 0.001) in the combined U.S./Multinational studies and from 4.9% to 0.5%
(90% relative risk reduction, p less than 0.001) in the Three-Year Study of FIT. In the
Four-Year Study of FIT, FOSAMAX reduced the percentage of osteoporotic women
experiencing multiple vertebral fractures from 0.6% to 0.1% (78% relative risk
reduction, p=0.035).
Thus, FOSAMAX reduced the incidence of radiographic vertebral fractures in
osteoporotic women whether or not they had a previous radiographic vertebral
fracture.
FOSAMAX, over a three- or four-year period, was associated with statistically
significant reductions in loss of height vs. placebo in patients with and
without baseline radiographic vertebral fractures. At the end of the FIT studies
the between-treatment group differences were 3.2 mm in the Three-Year Study and
1.3 mm in the Four-Year Study. Bone histology Bone histology in 270 postmenopausal patients with osteoporosis
treated with FOSAMAX at doses ranging from 1 to 20 mg/day for one, two, or three
years revealed normal mineralization and structure, as well as the expected
decrease in bone turnover relative to placebo. These data, together with the
normal bone histology and increased bone strength observed in rats and baboons
exposed to long-term alendronate treatment, support the conclusion that bone
formed during therapy with FOSAMAX is of normal quality. Men The efficacy of FOSAMAX in men with hypogonadal or idiopathic
osteoporosis was demonstrated in two clinical studies.
A two-year, double-blind, placebo-controlled, multicenter study of FOSAMAX 10
mg once daily enrolled a total of 241 men between the ages of 31 and 87 (mean,
63). All patients in the trial had either: 1) a BMD T-score less than or equal to -2 at the femoral
neck and ≤-1 at the lumbar spine, or 2) a baseline osteoporotic fracture and a
BMD T-score less than or equal to -1 at the femoral neck. At two years, the mean increases relative
to placebo in BMD in men receiving FOSAMAX 10 mg/day were significant at the
following sites: lumbar spine, 5.3%; femoral neck, 2.6%; trochanter, 3.1%; and
total body, 1.6%. Treatment with FOSAMAX also reduced height loss (FOSAMAX,
-0.6 mm vs. placebo, -2.4 mm).
A one-year, double-blind, placebo-controlled, multicenter study of once
weekly FOSAMAX 70 mg enrolled a total of 167 men between the ages of 38 and 91
(mean, 66). Patients in the study had either: 1) a BMD T-score less than or equal to -2 at the
femoral neck and less than or equal to -1 at the lumbar spine, 2) a BMD T-score less than or equal to -2 at the lumbar
spine and less than or equal to -1 at the femoral neck, or 3) a baseline osteoporotic fracture and a
BMD T-score less than or equal to -1 at the femoral neck. At one year, the mean increases relative to
placebo in BMD in men receiving FOSAMAX 70 mg once weekly were significant at
the following sites: lumbar spine, 2.8%; femoral neck, 1.9%; trochanter, 2.0%;
and total body, 1.2%. These increases in BMD were similar to those seen at one
year in the 10 mg once-daily study.
In both studies, BMD responses were similar regardless of age (greater than or equal to 65 years vs.
less than 65 years), gonadal function (baseline testosterone less than 9 ng/dL vs. greater than or equal to 9
ng/dL), or baseline BMD (femoral neck and lumbar spine T-score less than or equal to -2.5 vs.
greater than -2.5). Prevention of osteoporosis in postmenopausal
women
Prevention of bone loss was demonstrated in two double-blind,
placebo-controlled studies of postmenopausal women 40-60 years of age. One
thousand six hundred nine patients (FOSAMAX 5 mg/day; n=498) who were at least
six months postmenopausal were entered into a two-year study without regard to
their baseline BMD. In the other study, 447 patients (FOSAMAX 5 mg/day; n=88),
who were between six months and three years postmenopause, were treated for up
to three years. In the placebo-treated patients BMD losses of approximately 1%
per year were seen at the spine, hip (femoral neck and trochanter) and total
body. In contrast, FOSAMAX 5 mg/day prevented bone loss in the majority of
patients and induced significant increases in mean bone mass at each of these
sites (see figures below). In addition, FOSAMAX 5 mg/day reduced the rate of
bone loss at the forearm by approximately half relative to placebo. FOSAMAX
5 mg/day was similarly effective in this population regardless of age, time
since menopause, race and baseline rate of bone turnover.
Osteoporosis Prevention Studies in Postmenopausal
Women
The therapeutic equivalence of once weekly FOSAMAX 35 mg (n=362) and FOSAMAX
5 mg daily (n=361) was demonstrated in a one-year, double-blind, multicenter
study of postmenopausal women without osteoporosis. In the primary analysis of
completers, the mean increases from baseline in lumbar spine BMD at one year
were 2.9% (2.6, 3.2%; 95% CI) in the 35-mg once-weekly group (n=307) and 3.2%
(2.9, 3.5%; 95% CI) in the 5-mg daily group (n=298). The two treatment groups
were also similar with regard to BMD increases at other skeletal sites. The
results of the intention-to-treat analysis were consistent with the primary
analysis of completers.
Bone histology Bone histology was normal in the 28 patients biopsied at the end
of three years who received FOSAMAX at doses of up to 10 mg/day. Concomitant use with estrogen/hormone replacement
therapy (HRT) The effects on BMD of treatment with FOSAMAX 10 mg once daily and
conjugated estrogen (0.625 mg/day) either alone or in combination were assessed
in a two-year, double-blind, placebo-controlled study of hysterectomized
postmenopausal osteoporotic women (n=425). At two years, the increases in lumbar
spine BMD from baseline were significantly greater with the combination (8.3%)
than with either estrogen or FOSAMAX alone (both 6.0%).
The effects on BMD when FOSAMAX was added to stable doses (for at least one
year) of HRT (estrogen ± progestin) were assessed in a one-year, double-blind,
placebo-controlled study in postmenopausal osteoporotic women (n=428). The
addition of FOSAMAX 10 mg once daily to HRT produced, at one year, significantly
greater increases in lumbar spine BMD (3.7%) vs. HRT alone (1.1%).
In these studies, significant increases or favorable trends in BMD for
combined therapy compared with HRT alone were seen at the total hip, femoral
neck, and trochanter. No significant effect was seen for total body BMD.
Histomorphometric studies of transiliac biopsies in 92 subjects showed normal
bone architecture. Compared to placebo there was a 98% suppression of bone
turnover (as assessed by mineralizing surface) after 18 months of combined
treatment with FOSAMAX and HRT, 94% on FOSAMAX alone, and 78% on HRT alone. The
long-term effects of combined FOSAMAX and HRT on fracture occurrence and
fracture healing have not been studied. Glucocorticoid-induced osteoporosis
The efficacy of FOSAMAX 5 and 10 mg once daily in men and women
receiving glucocorticoids (at least 7.5 mg/day of prednisone or equivalent) was
demonstrated in two, one-year, double-blind, randomized, placebo-controlled,
multicenter studies of virtually identical design, one performed in the United
States and the other in 15 different countries (Multinational [which also
included FOSAMAX 2.5 mg/day]). These studies enrolled 232 and 328 patients,
respectively, between the ages of 17 and 83 with a variety of
glucocorticoid-requiring diseases. Patients received supplemental calcium and
vitamin D. The following figure shows the mean increases relative to placebo in
BMD of the lumbar spine, femoral neck, and trochanter in patients receiving
FOSAMAX 5 mg/day for each study.
Studies in Glucocorticoid-Treated Patients: Increase
in BMD: FOSAMAX 5 mg/day at One Year
After one year, significant increases relative to placebo in BMD were seen in
the combined studies at each of these sites in patients who received FOSAMAX
5 mg/day. In the placebo-treated patients, a significant decrease in BMD
occurred at the femoral neck (-1.2%), and smaller decreases were seen at the
lumbar spine and trochanter. Total body BMD was maintained with FOSAMAX
5 mg/day. The increases in BMD with FOSAMAX 10 mg/day were similar to those with
FOSAMAX 5 mg/day in all patients except for postmenopausal women not receiving
estrogen therapy. In these women, the increases (relative to placebo) with
FOSAMAX 10 mg/day were greater than those with FOSAMAX 5 mg/day at the lumbar
spine (4.1% vs. 1.6%) and trochanter (2.8% vs. 1.7%), but not at other sites.
FOSAMAX was effective regardless of dose or duration of glucocorticoid use. In
addition, FOSAMAX was similarly effective regardless of age (less than 65 vs.
greater than or equal to 65 years), race (Caucasian vs. other races), gender, underlying disease,
baseline BMD, baseline bone turnover, and use with a variety of common
medications.
Bone histology was normal in the 49 patients biopsied at the end of one year
who received FOSAMAX at doses of up to 10 mg/day.
Of the original 560 patients in these studies, 208 patients who remained on
at least 7.5 mg/day of prednisone or equivalent continued into a one-year
double-blind extension. After two years of treatment, spine BMD increased by
3.7% and 5.0% relative to placebo with FOSAMAX 5 and 10 mg/day, respectively.
Significant increases in BMD (relative to placebo) were also observed at the
femoral neck, trochanter, and total body.
After one year, 2.3% of patients treated with FOSAMAX 5 or 10 mg/day (pooled)
vs. 3.7% of those treated with placebo experienced a new vertebral fracture (not
significant). However, in the population studied for two years, treatment with
FOSAMAX (pooled dosage groups: 5 or 10 mg for two years or 2.5 mg for one year
followed by 10 mg for one year) significantly reduced the incidence of patients
with a new vertebral fracture (FOSAMAX 0.7% vs. placebo 6.8%). Paget's disease of bone
The efficacy of FOSAMAX 40 mg once daily for six months was
demonstrated in two double-blind clinical studies of male and female patients
with moderate to severe Paget's disease (alkaline phosphatase at least twice the
upper limit of normal): a placebo-controlled, multinational study and a U.S.
comparative study with etidronate disodium 400 mg/day. The following figure
shows the mean percent changes from baseline in serum alkaline phosphatase for
up to six months of randomized treatment.
Studies in Paget's Disease of Bone: Effect on Serum
Alkaline Phosphatase of FOSAMAX 40 mg/day Versus Placebo or Etidronate 400
mg/day
At six months the suppression in alkaline phosphatase in patients treated
with FOSAMAX was significantly greater than that achieved with etidronate and
contrasted with the complete lack of response in placebo-treated patients.
Response (defined as either normalization of serum alkaline phosphatase or
decrease from baseline greater than or equal to 60%) occurred in approximately 85% of patients treated
with FOSAMAX in the combined studies vs. 30% in the etidronate group and 0% in
the placebo group. FOSAMAX was similarly effective regardless of age, gender,
race, prior use of other bisphosphonates, or baseline alkaline phosphatase
within the range studied (at least twice the upper limit of normal).
Bone histology was evaluated in 33 patients with Paget's disease treated with
FOSAMAX 40 mg/day for 6 months. As in patients treated for osteoporosis (see Clinical Studies, Treatment of osteoporosis in
postmenopausal women, Bone histology), FOSAMAX did not impair
mineralization, and the expected decrease in the rate of bone turnover was
observed. Normal lamellar bone was produced during treatment with FOSAMAX, even
where preexisting bone was woven and disorganized. Overall, bone histology data
support the conclusion that bone formed during treatment with FOSAMAX is of
normal quality.
Animal Pharmacology
The relative inhibitory activities on bone resorption and mineralization of
alendronate and etidronate were compared in the Schenk assay, which is based on
histological examination of the epiphyses of growing rats. In this assay, the
lowest dose of alendronate that interfered with bone mineralization (leading to
osteomalacia) was 6000-fold the antiresorptive dose. The corresponding ratio for
etidronate was one to one. These data suggest that alendronate administered in
therapeutic doses is highly unlikely to induce osteomalacia.
Indications And Usage
FOSAMAX is indicated for:
Treatment and prevention of osteoporosis in postmenopausal women
For the treatment of osteoporosis, FOSAMAX increases bone mass and reduces
the incidence of fractures, including those of the hip and spine (vertebral
compression fractures). Osteoporosis may be confirmed by the finding of low bone
mass (for example, at least 2 standard deviations below the premenopausal mean)
or by the presence or history of osteoporotic fracture. (See CLINICAL PHARMACOLOGY, Pharmacodynamics.)
For the prevention of osteoporosis, FOSAMAX may be considered in
postmenopausal women who are at risk of developing osteoporosis and for whom the
desired clinical outcome is to maintain bone mass and to reduce the risk of
future fracture.
Bone loss is particularly rapid in postmenopausal women
younger than age 60. Risk factors often associated with the development of
postmenopausal osteoporosis include early menopause; moderately low bone mass
(for example, at least 1 standard deviation below the mean for healthy young
adult women); thin body build; Caucasian or Asian race; and family history of
osteoporosis. The presence of such risk factors may be important when
considering the use of FOSAMAX for prevention of osteoporosis.
Treatment to increase bone mass in men with osteoporosis
Treatment of glucocorticoid-induced osteoporosis in men and women receiving
glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone
and who have low bone mineral density (see PRECAUTIONS,
Glucocorticoid-induced osteoporosis). Patients treated with glucocorticoids
should receive adequate amounts of calcium and vitamin D.
Treatment of Paget's disease of bone in men and women
Treatment is indicated in patients with Paget's disease of bone having
alkaline phosphatase at least two times the upper limit of normal, or those who
are symptomatic, or those at risk for future complications from their disease.
Contraindications
Abnormalities of the esophagus which delay esophageal emptying such as
stricture or achalasia
Inability to stand or sit upright for at least 30 minutes
Patients at increased risk of aspiration should not receive FOSAMAX oral
solution.
FOSAMAX, like other bisphosphonates, may cause local irritation
of the upper gastrointestinal mucosa.
Esophageal adverse experiences, such as esophagitis, esophageal ulcers and
esophageal erosions, occasionally with bleeding and rarely followed by
esophageal stricture or perforation, have been reported in patients receiving
treatment with FOSAMAX. In some cases these have been severe and required
hospitalization. Physicians should therefore be alert to any signs or symptoms
signaling a possible esophageal reaction and patients should be instructed to
discontinue FOSAMAX and seek medical attention if they develop dysphagia,
odynophagia, retrosternal pain or new or worsening heartburn.
The risk of severe esophageal adverse experiences appears to be greater in
patients who lie down after taking FOSAMAX and/or who fail to swallow it with
the recommended amount of water, and/or who continue to take FOSAMAX after
developing symptoms suggestive of esophageal irritation. Therefore, it is very
important that the full dosing instructions are provided to, and understood by,
the patient (see DOSAGE AND ADMINISTRATION). In
patients who cannot comply with dosing instructions due to mental disability,
therapy with FOSAMAX should be used under appropriate supervision.
Because of possible irritant effects of FOSAMAX on the upper gastrointestinal
mucosa and a potential for worsening of the underlying disease, caution should
be used when FOSAMAX is given to patients with active upper gastrointestinal
problems (such as dysphagia, esophageal diseases, gastritis, duodenitis, or
ulcers).
There have been post-marketing reports of gastric and duodenal ulcers, some
severe and with complications, although no increased risk was observed in
controlled clinical trials.
Precautions
General Causes of osteoporosis other than estrogen deficiency, aging, and
glucocorticoid use should be considered.
Hypocalcemia must be corrected before initiating therapy with FOSAMAX (see CONTRAINDICATIONS). Other disorders affecting mineral
metabolism (such as vitamin D deficiency) should also be effectively treated. In
patients with these conditions, serum calcium and symptoms of hypocalcemia
should be monitored during therapy with FOSAMAX.
Presumably due to the effects of FOSAMAX on increasing bone mineral, small,
asymptomatic decreases in serum calcium and phosphate may occur, especially in
patients with Paget's disease, in whom the pretreatment rate of bone turnover
may be greatly elevated and in patients receiving glucocorticoids, in whom
calcium absorption may be decreased.
Ensuring adequate calcium and vitamin D intake is especially important in
patients with Paget's disease of bone and in patients receiving
glucocorticoids. Musculoskeletal Pain In post marketing experience, severe and occasionally
incapacitating bone, joint, and/or muscle pain has been reported in patients
taking bisphosphonates that are approved for the prevention and treatment of
osteoporosis (see ADVERSE REACTIONS). However, such
reports have been infrequent. This category of drugs includes FOSAMAX
(alendronate). Most of the patients were postmenopausal women. The time to onset
of symptoms varied from one day to several months after starting the drug.
Discontinue use if severe symptoms develop. Most patients had relief of symptoms
after stopping. A subset had recurrence of symptoms when rechallenged with the
same drug or another bisphosphonate.
In placebo-controlled clinical studies of FOSAMAX, the percentages of
patients with these symptoms were similar in the FOSAMAX and placebo
groups. Dental Osteonecrosis of the jaw, generally associated with tooth
extraction and/or local infection, often with delayed healing, has been reported
in patients taking bisphosphonates. Most reported cases of
bisphosphonate-associated osteonecrosis have been in cancer patients treated
with intravenous bisphosphonates, but some have occurred in patients with
postmenopausal osteoporosis. Known risk factors for osteonecrosis include a
diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy,
corticosteroids), poor oral hygiene, and co-morbid disorders (e.g., pre-existing
dental disease, anemia, coagulopathy, infection).
Patients who develop osteonecrosis of the jaw (ONJ) while on bisphosphonate
therapy should receive care by an oral surgeon. Dental surgery may exacerbate
the condition. For patients requiring dental procedures, there are no data
available to suggest whether discontinuation of bisphosphonate treatment reduces
the risk for ONJ. Clinical judgment of the treating physician should guide the
management plan of each patient based on individual benefit/risk
assessment. Renal insufficency FOSAMAX is not recommended for patients with renal insufficiency
(creatinine clearance less than 35 mL/min). (See DOSAGE AND
ADMINISTRATION.) Glucocorticoid-induced osteoporosis The risk versus benefit of FOSAMAX for treatment at daily dosages
of glucocorticoids less than 7.5 mg of prednisone or equivalent has not been
established (see INDICATIONS AND USAGE). Before
initiating treatment, the hormonal status of both men and women should be
ascertained and appropriate replacement considered.
A bone mineral density measurement should be made at the initiation of
therapy and repeated after 6 to 12 months of combined FOSAMAX and glucocorticoid
treatment.
The efficacy of FOSAMAX for the treatment of glucocorticoid-induced
osteoporosis has been shown in patients with a median bone mineral density which
was 1.2 standard deviations below the mean for healthy young adults.
The efficacy of FOSAMAX has been established in studies of two years'
duration. The greatest increase in bone mineral density occurred in the first
year with maintenance or smaller gains during the second year. Efficacy of
FOSAMAX beyond two years has not been studied.
The efficacy of FOSAMAX in respect to fracture prevention has been
demonstrated for vertebral fractures. However, this finding was based on very
few fractures that occurred primarily in postmenopausal women. The efficacy for
prevention of non-vertebral fractures has not been demonstrated. Information for PatientsGeneral Physicians should instruct their patients to read the patient
package insert before starting therapy with FOSAMAX and to reread it each time
the prescription is renewed.
Patients should be instructed to take supplemental calcium and vitamin D, if
daily dietary intake is inadequate. Weight-bearing exercise should be considered
along with the modification of certain behavioral factors, such as cigarette
smoking and/or excessive alcohol consumption, if these factors exist. Dosing Instructions Patients should be instructed that the expected benefits of
FOSAMAX may only be obtained when it is taken with plain water the first thing
upon arising for the day at least 30 minutes before the first food, beverage, or
medication of the day. Even dosing with orange juice or coffee has been shown to
markedly reduce the absorption of FOSAMAX (see CLINICAL
PHARMACOLOGY, Pharmacokinetics, Absorption).
To facilitate delivery to the stomach and thus reduce the potential for
esophageal irritation patients should be instructed to swallow each tablet of
FOSAMAX with a full glass of water (6-8 oz). To facilitate gastric emptying
patients should drink at least 2 oz (a quarter of a cup) of water after taking
FOSAMAX oral solution. Patients should be instructed not to lie down for at
least 30 minutes and until after their first food
of the day. Patients should not chew or suck on the tablet because of a
potential for oropharyngeal ulceration. Patients should be specifically
instructed not to take FOSAMAX at bedtime or before arising for the day.
Patients should be informed that failure to follow these instructions may
increase their risk of esophageal problems. Patients should be instructed that
if they develop symptoms of esophageal disease (such as difficulty or pain upon
swallowing, retrosternal pain or new or worsening heartburn) they should stop
taking FOSAMAX and consult their physician.
Patients should be instructed that if they miss a dose of once weekly
FOSAMAX, they should take one dose on the morning after they remember. They
should not take two doses on the same day but should return to taking one dose
once a week, as originally scheduled on their chosen day. Drug Interactions (also see CLINICAL PHARMACOLOGY,
Pharmacokinetics, Drug Interactions) Estrogen/hormone replacement therapy (HRT) Concomitant use of HRT (estrogen ± progestin) and FOSAMAX was
assessed in two clinical studies of one or two years' duration in postmenopausal
osteoporotic women. In these studies, the safety and tolerability profile of the
combination was consistent with those of the individual treatments; however, the
degree of suppression of bone turnover (as assessed by mineralizing surface) was
significantly greater with the combination than with either component alone. The
long-term effects of combined FOSAMAX and HRT on fracture occurrence have not
been studied (see CLINICAL PHARMACOLOGY, Clinical
Studies, Concomitant use with estrogen/hormone replacement therapy (HRT) and
ADVERSE REACTIONS, Clinical Studies, Concomitant use
with estrogen/hormone replacement therapy). Calcium Supplements/Antacids It is likely that calcium supplements, antacids, and some oral
medications will interfere with absorption of FOSAMAX. Therefore, patients must
wait at least one-half hour after taking FOSAMAX before taking any other oral
medications. Aspirin In clinical studies, the incidence of upper gastrointestinal
adverse events was increased in patients receiving concomitant therapy with
daily doses of FOSAMAX greater than 10 mg and aspirin-containing products. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) FOSAMAX may be administered to patients taking NSAIDs. In a
3-year, controlled, clinical study (n=2027) during which a majority of patients
received concomitant NSAIDs, the incidence of upper gastrointestinal adverse
events was similar in patients taking FOSAMAX 5 or 10 mg/day compared to those
taking placebo. However, since NSAID use is associated with gastrointestinal
irritation, caution should be used during concomitant use with FOSAMAX. Carcinogenesis, Mutagenesis,
Impairment of Fertility Harderian gland (a retro-orbital gland not present in humans)
adenomas were increased in high-dose female mice (p=0.003) in a 92-week oral
carcinogenicity study at doses of alendronate of 1, 3, and 10 mg/kg/day (males)
or 1, 2, and 5 mg/kg/day (females). These doses are equivalent to 0.12
to 1.2 times a maximum recommended daily dose of 40 mg (Paget's disease) based
on surface area, mg/m2. The relevance of this finding to
humans is unknown.
Parafollicular cell (thyroid) adenomas were increased in high-dose male rats
(p=0.003) in a 2-year oral carcinogenicity study at doses of 1 and 3.75 mg/kg
body weight. These doses are equivalent to 0.26 and 1 times a 40 mg human daily
dose based on surface area, mg/m2. The relevance of this
finding to humans is unknown.
Alendronate was not genotoxic in the in vitro
microbial mutagenesis assay with and without metabolic activation, in an in vitro mammalian cell mutagenesis assay, in an in vitro alkaline elution assay in rat hepatocytes, and in
an in vivo chromosomal aberration assay in mice. In
an in vitro chromosomal aberration assay in Chinese
hamster ovary cells, however, alendronate gave equivocal results.
Alendronate had no effect on fertility (male or female) in rats at oral doses
up to 5 mg/kg/day (1.3 times a 40 mg human daily dose based on surface area,
mg/m2). PregnancyPregnancy Category C: Reproduction studies in rats showed decreased postimplantation
survival at 2 mg/kg/day and decreased body weight gain in normal pups at 1
mg/kg/day. Sites of incomplete fetal ossification were statistically
significantly increased in rats beginning at 10 mg/kg/day in vertebral
(cervical, thoracic, and lumbar), skull, and sternebral bones. The above doses
ranged from 0.26 times (1 mg/kg) to 2.6 times (10 mg/kg) a maximum recommended
daily dose of 40 mg (Paget's disease) based on surface area, mg/m2. No similar fetal effects were seen when pregnant rabbits
were treated at doses up to 35 mg/kg/day (10.3 times a 40 mg human daily dose
based on surface area, mg/m2).
Both total and ionized calcium decreased in pregnant rats at 15 mg/kg/day
(3.9 times a 40 mg human daily dose based on surface area, mg/m2) resulting in delays and failures of delivery. Protracted
parturition due to maternal hypocalcemia occurred in rats at doses as low as
0.5 mg/kg/day (0.13 times a 40 mg human daily dose based on surface area,
mg/m2) when rats were treated from before mating through
gestation. Maternotoxicity (late pregnancy deaths) occurred in the female rats
treated with 15 mg/kg/day for varying periods of time ranging from treatment
only during pre-mating to treatment only during early, middle, or late
gestation; these deaths were lessened but not eliminated by cessation of
treatment. Calcium supplementation either in the drinking water or by minipump
could not ameliorate the hypocalcemia or prevent maternal and neonatal deaths
due to delays in delivery; calcium supplementation IV prevented maternal, but
not fetal deaths.
Bisphosphonates are incorporated into the bone matrix, from which they are
gradually released over a period of years. The amount of bisphosphonate
incorporated into adult bone, and hence, the amount available for release back
into the systemic circulation, is directly related to the dose and duration of
bisphosphonate use. There are no data on fetal risk in humans. However, there is
a theoretical risk of fetal harm, predominantly skeletal, if a woman becomes
pregnant after completing a course of bisphosphonate therapy. The impact of
variables such as time between cessation of bisphosphonate therapy to
conception, the particular bisphosphonate used, and the route of administration
(intravenous versus oral) on the risk has not been studied.
There are no studies in pregnant women. FOSAMAX should be used during
pregnancy only if the potential benefit justifies the potential risk to the
mother and fetus. Nursing Mothers It is not known whether alendronate is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
FOSAMAX is administered to nursing women. Pediatric Use The efficacy and safety of FOSAMAX were examined in a randomized,
double-blind, placebo-controlled two-year study of 139 pediatric patients, aged
4-18 years, with severe osteogenesis imperfecta. One-hundred-and-nine patients
were randomized to 5 mg FOSAMAX daily (weight less than 40 kg) or 10 mg FOSAMAX daily
(weight greater than or equal to 40 kg) and 30 patients to placebo. The mean baseline lumbar spine BMD
Z-score of the patients was -4.5. The mean change in lumbar spine BMD Z-score
from baseline to Month 24 was 1.3 in the FOSAMAX-treated patients and 0.1 in the
placebo-treated patients. Treatment with FOSAMAX did not reduce the risk of
fracture. Sixteen percent of the FOSAMAX patients who sustained a
radiologically-confirmed fracture by Month 12 of the study had delayed fracture
healing (callus remodeling) or fracture non-union when assessed radiographically
at Month 24 compared with 9% of the placebo-treated patients. In FOSAMAX-treated
patients, bone histomorphometry data obtained at Month 24 demonstrated decreased
bone turnover and delayed mineralization time; however, there were no
mineralization defects. There were no statistically significant differences
between the FOSAMAX and placebo groups in reduction of bone pain.
FOSAMAX is not indicated for use in children.
(For clinical adverse experiences in children, see ADVERSE REACTIONS, Clinical Studies, Osteogenesis
Imperfecta.) Geriatric Use Of the patients receiving FOSAMAX in the Fracture Intervention
Trial (FIT), 71% (n=2302) were greater than or equal to 65 years of age and 17% (n=550) were
greater than or equal to 75 years of age. Of the patients receiving FOSAMAX in the United States and
Multinational osteoporosis treatment studies in women, osteoporosis studies in
men, glucocorticoid-induced osteoporosis studies, and Paget's disease studies
(see CLINICAL PHARMACOLOGY, Clinical Studies), 45%,
54%, 37%, and 70%, respectively, were 65 years of age or over. No overall
differences in efficacy or safety were observed between these patients and
younger patients, but greater sensitivity of some older individuals cannot be
ruled out.
Adverse Reactions
Clinical Studies In clinical studies of up to five years in duration adverse
experiences associated with FOSAMAX usually were mild, and generally did not
require discontinuation of therapy.
FOSAMAX has been evaluated for safety in approximately 8000 postmenopausal
women in clinical studies. Treatment of osteoporosisPostmenopausal women In two identically designed, three-year, placebo-controlled,
double-blind, multicenter studies (United States and Multinational; n=994),
discontinuation of therapy due to any clinical adverse experience occurred in
4.1% of 196 patients treated with FOSAMAX 10 mg/day and 6.0% of 397 patients
treated with placebo. In the Fracture Intervention Trial (n=6459),
discontinuation of therapy due to any clinical adverse experience occurred in
9.1% of 3236 patients treated with FOSAMAX 5 mg/day for 2 years and 10 mg/day
for either one or two additional years and 10.1% of 3223 patients treated with
placebo. Discontinuations due to upper gastrointestinal adverse experiences
were: FOSAMAX, 3.2%; placebo, 2.7%. In these study populations, 49-54% had a
history of gastrointestinal disorders at baseline and 54-89% used nonsteroidal
anti-inflammatory drugs or aspirin at some time during the studies. Adverse
experiences from these studies considered by the investigators as possibly,
probably, or definitely drug related in ≥1% of patients treated with either
FOSAMAX or placebo are presented in the following table.
Osteoporosis Treatment Studies in Postmenopausal Women: Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in ≥1% of Patients
* 10 mg/day for three years
† 5 mg/day for 2 years and 10 mg/day for either 1 or 2 additional years
Rarely, rash and erythema have occurred.
One patient treated with FOSAMAX (10 mg/day), who had a history of peptic
ulcer disease and gastrectomy and who was taking concomitant aspirin developed
an anastomotic ulcer with mild hemorrhage, which was considered drug related.
Aspirin and FOSAMAX were discontinued and the patient recovered.
The adverse experience profile was similar for the 401 patients treated with
either 5 or 20 mg doses of FOSAMAX in the United States and Multinational
studies. The adverse experience profile for the 296 patients who received
continued treatment with either 5 or 10 mg doses of FOSAMAX in the two-year
extension of these studies (treatment years 4 and 5) was similar to that
observed during the three-year placebo-controlled period. During the extension
period, of the 151 patients treated with FOSAMAX 10 mg/day, the proportion of
patients who discontinued therapy due to any clinical adverse experience was
similar to that during the first three years of the study.
In a one-year, double-blind, multicenter study, the overall safety and
tolerability profiles of once weekly FOSAMAX 70 mg and FOSAMAX 10 mg daily were
similar. The adverse experiences considered by the investigators as possibly,
probably, or definitely drug related in ≥1% of patients in either treatment
group are presented in the following
table.
Osteoporosis Treatment Studies in Postmenopausal Women: Adverse
Experiences Considered Possibly, Probably, or Definitely Drug Related by the
Investigators and Reported in ≥1% of Patients
Men In two placebo-controlled, double-blind, multicenter studies in
men (a two-year study of FOSAMAX 10 mg/day and a one-year study of once weekly
FOSAMAX 70 mg) the rates of discontinuation of therapy due to any clinical
adverse experience were 2.7% for FOSAMAX 10 mg/day vs. 10.5% for placebo, and
6.4% for once weekly FOSAMAX 70 mg vs. 8.6% for placebo. The adverse experiences
considered by the investigators as possibly, probably, or definitely drug
related in ≥2% of patients treated with either FOSAMAX or placebo are presented
in the following table.
Osteoporosis Studies in Men: Adverse Experiences Considered Possibly,
Probably, or Definitely Drug Related by the Investigators and Reported in ≥2% of
Patients
Prevention of osteoporosis in postmenopausal
women The safety of FOSAMAX 5 mg/day in postmenopausal women 40-60
years of age has been evaluated in three double-blind, placebo-controlled
studies involving over 1,400 patients randomized to receive FOSAMAX for either
two or three years. In these studies the overall safety profiles of FOSAMAX
5 mg/day and placebo were similar. Discontinuation of therapy due to any
clinical adverse experience occurred in 7.5% of 642 patients treated with
FOSAMAX 5 mg/day and 5.7% of 648 patients treated with placebo.
In a one-year, double-blind, multicenter study, the overall safety and
tolerability profiles of once weekly FOSAMAX 35 mg and FOSAMAX 5 mg daily were
similar.
The adverse experiences from these studies considered by the investigators as
possibly, probably, or definitely drug related in ≥1% of patients treated with
either once weekly FOSAMAX 35 mg, FOSAMAX 5 mg/day or placebo are presented in
the following table.
Osteoporosis Prevention Studies in Postmenopausal Women: Adverse
Experiences Considered Possibly, Probably, or Definitely Drug Related by the
Investigators and Reported in ≥1% of Patients
Musculoskeletal
musculoskeletal (bone, muscle or joint) pain
0.8
0.9
1.9
2.2
Concomitant use with estrogen/hormone replacement
therapy In two studies (of one and two years' duration) of postmenopausal
osteoporotic women (total: n=853), the safety and tolerability profile of
combined treatment with FOSAMAX 10 mg once daily and estrogen ± progestin
(n=354) was consistent with those of the individual treatments. Treatment of glucocorticoid-induced osteoporosis In two, one-year, placebo-controlled, double-blind, multicenter
studies in patients receiving glucocorticoid treatment, the overall safety and
tolerability profiles of FOSAMAX 5 and 10 mg/day were generally similar to that
of placebo. The adverse experiences considered by the investigators as possibly,
probably, or definitely drug related in ≥1% of patients treated with either
FOSAMAX 5 or 10 mg/day or placebo are presented in the following table.
One-Year Studies in Glucocorticoid-Treated Patients: Adverse
Experiences Considered Possibly, Probably, or Definitely Drug Related by the
Investigators and Reported in ≥1% of Patients
The overall safety and tolerability profile in the glucocorticoid-induced
osteoporosis population that continued therapy for the second year of the
studies (FOSAMAX: n=147) was consistent with that observed in the first
year. Paget's disease of bone In clinical studies (osteoporosis and Paget's disease), adverse
experiences reported in 175 patients taking FOSAMAX 40 mg/day for 3-12 months
were similar to those in postmenopausal women treated with FOSAMAX 10 mg/day.
However, there was an apparent increased incidence of upper gastrointestinal
adverse experiences in patients taking FOSAMAX 40 mg/day (17.7% FOSAMAX vs.
10.2% placebo). One case of esophagitis and two cases of gastritis resulted in
discontinuation of treatment.
Additionally, musculoskeletal (bone, muscle or joint) pain, which has been
described in patients with Paget's disease treated with other bisphosphonates,
was considered by the investigators as possibly, probably, or definitely drug
related in approximately 6% of patients treated with FOSAMAX 40 mg/day versus
approximately 1% of patients treated with placebo, but rarely resulted in
discontinuation of therapy. Discontinuation of therapy due to any clinical
adverse experience occurred in 6.4% of patients with Paget's disease treated
with FOSAMAX 40 mg/day and 2.4% of patients treated with placebo. Osteogenesis Imperfecta FOSAMAX is not indicated for use in children.
The overall safety profile of FOSAMAX in OI patients treated for up to 24
months was generally similar to that of adults with osteoporosis treated with
FOSAMAX. However, there was an increased occurrence of vomiting in OI patients
treated with FOSAMAX compared to placebo. During the 24-month treatment period,
vomiting was observed in 32 of 109 (29.4%) patients treated with FOSAMAX and 3
of 30 (10%) patients treated with placebo.
In a pharmacokinetic study, 6 of 24 pediatric OI patients who received a
single oral dose of FOSAMAX 35 or 70 mg developed fever, flu-like symptoms,
and/or mild lymphocytopenia within 24 to 48 hours after administration. These
events, lasting no more than 2 to 3 days and responding to acetaminophen, are
consistent with an acute-phase response that has been reported in patients
receiving bisphosphonates, including FOSAMAX. See ADVERSE
REACTIONS, Post-Marketing Experience, Body as a Whole. Laboratory Test Findings In double-blind, multicenter, controlled studies, asymptomatic,
mild, and transient decreases in serum calcium and phosphate were observed in
approximately 18% and 10%, respectively, of patients taking FOSAMAX versus
approximately 12% and 3% of those taking placebo. However, the incidences of
decreases in serum calcium to less than 8.0 mg/dL (2.0 mM) and serum phosphate to
less than or equal to 2.0 mg/dL (0.65 mM) were similar in both treatment groups. Post-Marketing Experience The following adverse reactions have been reported in
post-marketing use:
Body as a Whole: hypersensitivity reactions
including urticaria and rarely angioedema. Transient symptoms of myalgia,
malaise, asthenia and rarely, fever have been reported with FOSAMAX, typically
in association with initiation of treatment. Rarely, symptomatic hypocalcemia
has occurred, generally in association with predisposing conditions. Rarely,
peripheral edema.
Gastrointestinal: esophagitis, esophageal
erosions, esophageal ulcers, rarely esophageal stricture or perforation, and
oropharyngeal ulceration. Gastric or duodenal ulcers, some severe and with
complications have also been reported (see WARNINGS, PRECAUTIONS, Information for Patients, and DOSAGE AND ADMINISTRATION).
Localized osteonecrosis of the jaw, generally associated with tooth
extraction and/or local infection, often with delayed healing, has been reported
rarely (see PRECAUTIONS, Dental).
Musculoskeletal: bone, joint, and/or muscle pain,
occasionally severe, and rarely incapacitating (see PRECAUTIONS, Musculoskeletal Pain); joint swelling.
Nervous system: dizziness and vertigo.
Skin: rash (occasionally with photosensitivity),
pruritus, alopecia, rarely severe skin reactions, including Stevens-Johnson
syndrome and toxic epidermal necrolysis.
Special Senses: rarely uveitis, scleritis or
episcleritis.
Overdosage
Significant lethality after single oral doses was seen in female
rats and mice at 552 mg/kg (3256 mg/m2) and 966 mg/kg
(2898 mg/m2), respectively. In males, these values were
slightly higher, 626 and 1280 mg/kg, respectively. There was no lethality in
dogs at oral doses up to 200 mg/kg (4000 mg/m2).
No specific information is available on the treatment of overdosage with
FOSAMAX. Hypocalcemia, hypophosphatemia, and upper gastrointestinal adverse
events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer, may
result from oral overdosage. Milk or antacids should be given to bind
alendronate. Due to the risk of esophageal irritation, vomiting should not be
induced and the patient should remain fully upright.
Dialysis would not be beneficial.
Dosage And Administration
FOSAMAX must be taken at least
one-half hour before the first food, beverage, or medication of the day with
plain water only (see PRECAUTIONS, Information for
Patients). Other beverages (including mineral water), food, and some
medications are likely to reduce the absorption of FOSAMAX (see PRECAUTIONS, Drug Interactions). Waiting less than 30
minutes, or taking FOSAMAX with food, beverages (other than plain water) or
other medications will lessen the effect of FOSAMAX by decreasing its absorption
into the body.
FOSAMAX should only be taken upon arising for the day. To facilitate delivery
to the stomach and thus reduce the potential for esophageal irritation, a
FOSAMAX tablet should be swallowed with a full glass of water (6-8 oz). To
facilitate gastric emptying FOSAMAX oral solution should be followed by at least
2 oz (a quarter of a cup) of water. Patients should not lie down for at least 30
minutes and until after their first food of the
day. FOSAMAX should not be taken at bedtime or before arising for the day.
Failure to follow these instructions may increase the risk of esophageal adverse
experiences (see WARNINGS, PRECAUTIONS, Information for Patients).
Patients should receive supplemental calcium and vitamin D, if dietary intake
is inadequate (see PRECAUTIONS, General).
No dosage adjustment is necessary for the elderly or for patients with
mild-to-moderate renal insufficiency (creatinine clearance 35 to 60 mL/min).
FOSAMAX is not recommended for patients with more severe renal insufficiency
(creatinine clearance less than 35 mL/min) due to lack of experience. Treatment of osteoporosis in postmenopausal women
(see INDICATIONS AND USAGE)
The recommended dosage is:
one 70 mg tablet once weekly or
one bottle of 70 mg oral solution once weekly or
one 10 mg tablet once daily
Treatment to increase bone mass in men with
osteoporosis The recommended dosage is:
The safety of treatment and prevention of osteoporosis with FOSAMAX has been
studied for up to 7 years. Treatment of glucocorticoid-induced osteoporosis in
men and women The recommended dosage is one 5 mg tablet once daily, except for
postmenopausal women not receiving estrogen, for whom the recommended dosage is
one 10 mg tablet once daily. Paget's disease of bone in men and women The recommended treatment regimen is 40 mg once a day for six
months. Retreatment of Paget's disease In clinical studies in which patients were followed every six
months, relapses during the 12 months following therapy occurred in 9% (3 out of
32) of patients who responded to treatment with FOSAMAX. Specific retreatment
data are not available, although responses to FOSAMAX were similar in patients
who had received prior bisphosphonate therapy and those who had not. Retreatment
with FOSAMAX may be considered, following a six-month post-treatment evaluation
period in patients who have relapsed, based on increases in serum alkaline
phosphatase, which should be measured periodically. Retreatment may also be
considered in those who failed to normalize their serum alkaline phosphatase.
How Supplied
No. 3759 — Tablets FOSAMAX, 5 mg, are white, round, uncoated
tablets with an outline of a bone image on one side and code MRK 925 on the
other. They are supplied as follows:
NDC 54868-4384-0 bottles of 30.
No. 3797 — Tablets FOSAMAX, 10 mg, are white, oval, wax-polished tablets with
code MRK on one side and 936 on the other. They are supplied as follows:
NDC 54868-3857-0 bottles of 30.
No. 3813 — Tablets FOSAMAX, 35 mg, are white, oval, uncoated tablets with
code 77 on one side and a bone image on the other. They are supplied as
follows:
NDC 54868-4463-0 bottle of 4.
No. 3814 — Tablets FOSAMAX, 70 mg, are white, oval, uncoated tablets with
code 31 on one side and an outline of a bone image on the other. They are
supplied as follows:
NDC 54868-4462-0 bottle of 4
NDC 54868-4462-1 bottle of 12.
Storage FOSAMAX Tablets:
Store in a well-closed container at room temperature, 15-30°C (59-86°F).
FOSAMAX Oral Solution:
Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). [See USP
Controlled Room Temperature.] Do not freeze.
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
Issued February 2008
Printed in USA
9635608
9636808
Supplemental Patient Material
Patient Information
Once Weekly FOSAMAX®
(FOSS-ah-max)
You must take once weekly FOSAMAX exactly as directed to
help make sure it works and to help lower the chance of problems in your
esophagus (the tube that connects your mouth and stomach).
(See “ How should I take once weekly
FOSAMAX?”).
If you have chest pain, new or worsening heartburn, or have
trouble or pain when you swallow, stop taking FOSAMAX and call your doctor.
(See “ What are the possible
side effects of FOSAMAX?”).
What is FOSAMAX?
FOSAMAX is a prescription medicine for:
The treatment or prevention of osteoporosis (thinning of bone) in women
after menopause. It reduces the chance of having a hip or spinal fracture
(break).
Treatment to increase bone mass in men with osteoporosis.
FOSAMAX tablets are for treatment and prevention of osteoporosis.
FOSAMAX oral solution is for treatment of osteoporosis.
Improvement in bone density may be observed as early as 3 months after you
start taking FOSAMAX even though you won’t see or feel a difference. For FOSAMAX
to continue to work, you need to keep taking it.
FOSAMAX is not a hormone.
There is more information about osteoporosis at the end of this leaflet.
Who should not take FOSAMAX?
Do not take FOSAMAX (tablets or oral solution) if you:
Have certain problems with your esophagus, the tube that connects your mouth
with your stomach
Cannot stand or sit upright for at least 30 minutes
Have low levels of calcium in your blood
Are allergic to FOSAMAX or any of its ingredients. A ul of ingredients is
at the end of this leaflet.
Do not take FOSAMAX oral solution if you have trouble swallowing liquids.
What should I tell my doctor before
using FOSAMAX?
Tell your doctor about all of your medical
conditions, including if you:
have problems with swallowing
have stomach or digestive problems
have kidney problems
are pregnant or planning to become pregnant. It is
not known if FOSAMAX can harm your unborn baby.
are breastfeeding. It is not known if FOSAMAX passes
into your milk and if it can harm your baby.
Tell your doctor about all medicines you take, including prescription and
non-prescription medicines, vitamins, and herbal supplements.
Know the medicines you take. Keep a ul of them and show it to your doctor
and pharmacist each time you get a new medicine. How should I take once weekly
FOSAMAX?
Choose the day of the week that best fits your schedule.
Take 1 dose of FOSAMAX every week on your chosen day after you get up for the day and before taking your first food, drink, or other medicine
Take FOSAMAX while you are sitting or standing.
Take your FOSAMAX with plain water only as
follows:
TABLETS: Swallow one tablet with a full glass (6-8
oz) of plain water.
ORAL SOLUTION: Drink one entire bottle of solution
followed by at least 2 ounces (a quarter of a cup) of plain water.
Do not take FOSAMAX with:
Mineral waterCoffee or teaJuice
FOSAMAX works only if it is taken on an empty stomach.
Do not chew or suck on a tablet of FOSAMAX.
After taking your FOSAMAX, wait at least 30 minutes:
before you lie down. You may sit, stand or walk, and do normal activities
like reading.
before you take your first food or drink except for plain water.
before you take other medicines, including antacids, calcium, and other
supplements and vitamins.
Do not lie down until after your first food of the
day.
It is important that you keep taking FOSAMAX for as long as your doctor says
to take it. For FOSAMAX to continue to work, you need to keep taking it.
What should I do if I miss a dose of
FOSAMAX or if I take too many?
If you miss a dose, take only 1 dose of FOSAMAX on the morning after you
remember. Do not take 2 doses on the same day. Continue your usual schedule of 1
dose once a week on your chosen day.
If you think you took more than the prescribed dose of FOSAMAX, drink a full
glass of milk and call your doctor right away. Do not try to vomit. Do not lie
down.
What should I avoid while taking
FOSAMAX?
Do not eat, drink, or take other medicines or supplements before taking FOSAMAX.
Wait for at least 30 minutes after taking FOSAMAX to
eat, drink, or take other medicines or supplements.
Do not lie down for at least 30 minutes after taking
FOSAMAX. Do not lie down until after your first food of
the day.
What are the possible side effects
of FOSAMAX?
FOSAMAX may cause problems in your esophagus
(the tube that connects the mouth and stomach). (See “ What is the most important information I should know
about once weekly FOSAMAX?”.) These problems include irritation,
inflammation, or ulcers of the esophagus, which may sometimes bleed. This may
occur especially if you do not drink a full glass of water with FOSAMAX or if
you lie down in less than 30 minutes or before your first food of the day.
Stop taking FOSAMAX and call your doctor right away if you
get any of these signs of possible serious problems of the esophagus:
Chest pain
New or worsening heartburn
Trouble or pain when swallowing
Esophagus problems may get worse if you continue to take FOSAMAX.
Mouth sores (ulcers) may occur if the FOSAMAX tablet is chewed or dissolved
in the mouth.
You may get flu-like symptoms, typically at the start of treatment with
FOSAMAX.
You may get allergic reactions, such as hives or, in rare cases, swelling of
your face, lips, tongue, or throat.
FOSAMAX may cause jaw-bone problems in some people. Jaw-bone problems may
include infection, and delayed healing after teeth are pulled.
The most common side effect is stomach area (abdominal) pain. Less common
side effects are nausea, vomiting, a full or bloated feeling in the stomach,
constipation, diarrhea, black or bloody stools (bowel movements), gas, eye pain,
rash that may be made worse by sunlight, hair loss, headache, dizziness, a
changed sense of taste, joint swelling or swelling in the hands or legs, and
bone, muscle, or joint pain.
Call your doctor if you develop severe bone, muscle, or
joint pain.
Tell your doctor about any side effect that bothers you or that does not go
away.
These are not all the side effects with FOSAMAX. Ask your doctor or
pharmacist for more information. How do I store FOSAMAX?
Store at room temperature, 59 to 86°F (15 to 30°C).
Safely discard FOSAMAX that is out-of-date or no longer needed.
Keep FOSAMAX and all medicines out of the reach of
children.
General information about using
FOSAMAX safely and effectively
Medicines are sometimes prescribed for conditions that are not
mentioned in patient information leaflets. Do not use FOSAMAX for a condition
for which it was not prescribed. Do not give FOSAMAX to other people, even if
they have the same symptoms you have. It may harm them.
FOSAMAX is not indicated for use in children.
This leaflet is a summary of information about FOSAMAX. If you have any
questions or concerns about FOSAMAX or osteoporosis, talk to your doctor,
pharmacist, or other health care provider. You can ask your doctor or pharmacist
for information about FOSAMAX written for health care providers. For more
information, call 1-877-408-4699 (toll-free) or visit the following website: www.fosamax.com. What are the ingredients in
FOSAMAX?
TabletsFOSAMAX tablets contain alendronate sodium as the
active ingredient and the following inactive ingredients: cellulose, lactose,
croscarmellose sodium and magnesium stearate.
Oral SolutionFosamax oral solution contains alendronate sodium as the
active ingredient and the following inactive ingredients: sodium citrate, citric
acid, sodium saccharin, artificial raspberry flavor, purified water, sodium
propylparaben and sodium butylparaben. What should I know about
osteoporosis?
Normally your bones are being rebuilt all the time. First, old
bone is removed (resorbed). Then a similar amount of new bone is formed. This
balanced process keeps your skeleton healthy and strong.
Osteoporosis is a thinning and weakening of the bones. It is common in women
after menopause, and may also occur in men. In osteoporosis, bone is removed
faster than it is formed, so overall bone mass is lost and bones become weaker.
Therefore, keeping bone mass is important to keep your bones healthy. In both
men and women, osteoporosis may also be caused by certain medicines called
corticosteroids.
At first, osteoporosis usually has no symptoms, but it can cause fractures
(broken bones). Fractures usually cause pain. Fractures of the bones of the
spine may not be painful, but over time they can make you shorter. Eventually,
your spine can curve and your body can become bent over. Fractures may happen
during normal, everyday activity, such as lifting, or from minor injury that
would normally not cause bones to break. Fractures most often occur at the hip,
spine, or wrist. This can lead to pain, severe disability, or loss of ability to
move around (mobility). Who is at risk for
osteoporosis?
Many things put people at risk of osteoporosis. The following
people have a higher chance of getting osteoporosis:
Women who:
Are going through or who are past menopause
Men who:
Are elderly
People who:
Are white (Caucasian) or oriental (Asian)
Are thin
Have family member with osteoporosis
Do not get enough calcium or vitamin D
Do not exercise
Smoke
Drink alcohol often
Take bone thinning medicines (like prednisone or other corticosteroids) for
a long time
What can I do to help prevent or
treat osteoporosis?
In addition to FOSAMAX, your doctor may suggest one or more of
the following lifestyle changes:
Stop smoking. Smoking may increase your chance of
getting osteoporosis.
Reduce the use of alcohol. Too much alcohol may
increase the risk of osteoporosis and injuries that can cause fractures.
Exercise regularly. Like muscles, bones need
exercise to stay strong and healthy. Exercise must be safe to prevent injuries,
including fractures. Talk with your doctor before you begin any exercise
program.
Eat a balanced diet. Having enough calcium in your
diet is important. Your doctor can advise you whether you need to change your
diet or take any dietary supplements, such as calcium or vitamin D.
Rx only
MERCK & CO., INC.Whitehouse Station, NJ 08889, USA
You must take FOSAMAX exactly as directed to help make sure
it works and to help lower the chance of problems in your esophagus (the tube
that connects your mouth and stomach).
(See “How should I take FOSAMAX?”).
If you have chest pain, new or worsening heartburn, or have
trouble or pain when you swallow, stop taking FOSAMAX and call your
doctor.
(See “ What are the
possible side effects of FOSAMAX?”).
What is FOSAMAX?
FOSAMAX is a prescription medicine for:
The treatment or prevention of osteoporosis (thinning of bone) in women
after menopause. It reduces the chance of having a hip or spinal fracture
(break).
Treatment to increase bone mass in men with osteoporosis.
The treatment of osteoporosis in either men or women who are taking
corticosteroid medicines (for example, prednisone).
Improvement in bone density may be observed as early as 3 months after you
start taking FOSAMAX even though you won’t see or feel a difference. For FOSAMAX
to continue to work, you need to keep taking it.
FOSAMAX is not a hormone.
There is more information about osteoporosis at the end of this
leaflet. Who should not take FOSAMAX?
Do not take FOSAMAX if you:
Have certain problems with your esophagus, the tube that connects your mouth
with your stomach
Cannot stand or sit upright for at least 30 minutes
Have low levels of calcium in your blood
Are allergic to FOSAMAX or any of its ingredients. A ul of ingredients is
at the end of this leaflet.
What should I tell my doctor before
using FOSAMAX?
Tell your doctor about all of your medical
conditions, including if you:
have problems with swallowing
have stomach or digestive problems
have kidney problems
are pregnant or planning to become pregnant. It is
not known if FOSAMAX can harm your unborn baby.
are breastfeeding. It is not known if FOSAMAX passes
into your milk and if it can harm your baby.
Tell your doctor about all medicines you take, including prescription and
non-prescription medicines, vitamins, and herbal supplements.
Know the medicines you take. Keep a ul of them and show it to your doctor
and pharmacist each time you get a new medicine. How should I take FOSAMAX?
Take 1 FOSAMAX tablet once a day, every day after
you get up for the day and before taking your first
food, drink, or other medicine.
Take FOSAMAX while you are sitting or standing.
Swallow your FOSAMAX tablet with a full glass (6-8 oz) of plain water only.
Do not take FOSAMAX with:
Mineral waterCoffee or teaJuice
FOSAMAX works only if taken on an empty stomach.
Do not chew or suck on a tablet of FOSAMAX.
After swallowing your FOSAMAX tablet, wait at least 30 minutes:
before you lie down. You may sit, stand or walk, and do normal activities
like reading.
before you take your first food or drink except for plain water.
before you take other medicines, including antacids, calcium, and other
supplements and vitamins.
Do not lie down until after first food of the day.
It is important that you keep taking FOSAMAX for as long as your doctor says
to take it. For FOSAMAX to continue to work, you need to keep taking it.
What should I do if I miss a dose of
FOSAMAX or if I take too many?
If you miss a dose, do not take it later in the day. Continue your usual
schedule of 1 tablet once a day the next morning.
If you think you took more than the prescribed dose of FOSAMAX, drink a full
glass of milk and call your doctor right away. Do not try to vomit. Do not lie
down.
What should I avoid while taking
FOSAMAX?
Do not eat, drink, or take other medicines or supplements before taking FOSAMAX.
Wait for at least 30 minutes after taking FOSAMAX to
eat, drink, or take other medicines or supplements.
Do not lie down for at least 30 minutes after taking
FOSAMAX. Do not lie down until after your first food of
the day.
What are the possible side effects
of FOSAMAX?
FOSAMAX may cause problems in your esophagus
(the tube that connects the mouth and stomach). (See “ What is the most important information I should know
about FOSAMAX?”.) These problems include irritation, inflammation, or ulcers
of the esophagus, which may sometimes bleed. This may occur especially if you do
not drink a full glass of water with FOSAMAX or if you lie down in less than 30
minutes or before your first food of the day.
Stop taking FOSAMAX and call your doctor right away if you
get any of these signs of possible serious problems of the esophagus:
Chest pain
New or worsening heartburn
Trouble or pain when swallowing
Esophagus problems may get worse if you continue to take FOSAMAX.
Mouth sores (ulcers) may occur if the FOSAMAX tablet is chewed or dissolved
in the mouth.
You may get flu-like symptoms typically at the start of treatment with
FOSAMAX.
You may get allergic reactions, such as hives or, in rare cases, swelling of
your face, lips, tongue, or throat.
FOSAMAX may cause jaw-bone problems in some people. Jaw-bone problems
include infection, and delayed healing after teeth are pulled.
The most common side effect is stomach area (abdominal) pain. Less common
side effects are nausea, vomiting, a full or bloated feeling in the stomach,
constipation, diarrhea, black or bloody stools (bowel movements), gas, eye pain,
rash that may be made worse by sunlight, hair loss, headache, dizziness, a
changed sense of taste, joint swelling or swelling in the hands or legs, and
bone, muscle, or joint pain.
Call your doctor if you develop severe bone, muscle, or
joint pain.
Tell your doctor about any side effect that bothers you or that does not go
away.
These are not all the side effects with FOSAMAX. Ask your doctor or
pharmacist for more information. How do I store FOSAMAX?
Store FOSAMAX at room temperature, 59 to 86°F (15 to 30°C).
Safely discard FOSAMAX that is out-of-date or no longer needed.
Keep FOSAMAX and all medicines out of the reach of
children.
General information about using
FOSAMAX safely and effectively
Medicines are sometimes prescribed for conditions that are not
mentioned in patient information leaflets. Do not use FOSAMAX for a condition
for which it was not prescribed. Do not give FOSAMAX to other people, even if
they have the same symptoms you have. It may harm them.
FOSAMAX is not indicated for use in children.
This leaflet is a summary of information about FOSAMAX. If you have any
questions or concerns about FOSAMAX or osteoporosis, talk to your doctor,
pharmacist, or other health care provider. You can ask your doctor or pharmacist
for information about FOSAMAX written for health care providers. For more
information, call 1-877-408-4699 (toll-free) or visit the following website: www.fosamax.com. What are the ingredients in
FOSAMAX?
FOSAMAX contains alendronate sodium as the active ingredient and
the following inactive ingredients: cellulose, lactose, croscarmellose sodium
and magnesium stearate. The 10 mg tablet also contains carnauba wax. What should I know about
osteoporosis?
Normally your bones are being rebuilt all the time. First, old
bone is removed (resorbed). Then a similar amount of new bone is formed. This
balanced process keeps your skeleton healthy and strong.
Osteoporosis is a thinning and weakening of the bones. It is common in women
after menopause, and may also occur in men. In osteoporosis, bone is removed
faster than it is formed, so overall bone mass is lost and bones become weaker.
Therefore, keeping bone mass is important to keep your bones healthy. In both
men and women, osteoporosis may also be caused by certain medicines called
corticosteroids.
At first, osteoporosis usually has no symptoms, but it can cause fractures
(broken bones). Fractures usually cause pain. Fractures of the bones of the
spine may not be painful, but over time they can make you shorter. Eventually,
your spine can curve and your body can become bent over. Fractures may happen
during normal, everyday activity, such as lifting, or from minor injury that
would normally not cause bones to break. Fractures most often occur at the hip,
spine, or wrist. This can lead to pain, severe disability, or loss of ability to
move around (mobility). Who is at risk for
osteoporosis?
Many things put people at risk of osteoporosis. The following
people have a higher chance of getting osteoporosis:
Women who:
Are going through or who are past menopause
Men who:
Are elderly
People who:
Are white (Caucasian) or oriental (Asian)
Are thin
Have family member with osteoporosis
Do not get enough calcium or vitamin D
Do not exercise
Smoke
Drink alcohol often
Take bone thinning medicines (like prednisone or other corticosteroids) for
a long time
What can I do to help prevent or
treat osteoporosis?
In addition to FOSAMAX, your doctor may suggest one or more of
the following lifestyle changes:
Stop smoking. Smoking may increase your chance of
getting osteoporosis.
Reduce the use of alcohol. Too much alcohol may
increase the risk of osteoporosis and injuries that can cause fractures.
Exercise regularly. Like muscles, bones need
exercise to stay strong and healthy. Exercise must be safe to prevent injuries,
including fractures. Talk with your doctor before you begin any exercise
program.
Eat a balanced diet. Having enough calcium in your
diet is important. Your doctor can advise you whether you need to change your
diet or take any dietary supplements, such as calcium or vitamin D.
Rx Only
MERCK & CO., INC.Whitehouse Station, NJ 08889, USA
Issued February 2008
9636808
Principal Display Panel
FOSAMAX, Tablets, 5 mg
FOSAMAX, Tablets, 10 mg
FOSAMAX, Tablets, 35 mg
FOSAMAX, Tablets, 70 mg
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