Download Aldren PI philippines 02.02.11

the drug in pediatric patients have not been established.
DRUG INTERACTIONS
It is likely that calcium supplements, antacids, and some oral
medications will interfere with absorption of alendronate
sodium. Therefore, patients must wait at least one-half hour
after taking alendronate sodium tablets before taking any
other oral medications. In clinical studies, the incidence of
upper gastrointestinal adverse events was increased in
patients receiving concomitant therapy with daily doses of
alendronate sodium greater than 10 mg and aspirin-containing
products. Since NSAID use is associated with gastrointestinal
irritation, caution should be used during concomitant use with
alendronate sodium tablets. Intravenous ranitidine was shown
to double the bioavailability of oral alendronate sodium. The
clinical significance of this increased bioavailability and
whether similar increases will occur in patients given oral H2antagonists 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 sodium (a mean increase ranging from 20 to
44%).
OVERDOSAGE
No specific information is available on the treatment of
overdosage with alendronate sodium. 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 sodium. Due to
the risk of esophageal irritation, vomiting should not be
induced and the patient should remain fully upright. Dialysis
would not be beneficial.
CAUTION
Foods, Drugs, Devices and Cosmetics Act prohibits
dispensing without prescription.
STORAGE
0
STORE AT TEMPERATURES NOT EXCEEDING 25 C
PROTECT FROM LIGHT AND MOISTURE
KEEP OUT OF REACH OF CHILDREN
AVAILABILITY
In Alu-Alu Blister Pack x 4's (Box of 4's)
Manufactured by:
Cadila Healthcare Limited.
Sarkhej-Bavla N.H. No. 8 A,
Moraiya, Tal : Sanand,
Dist : Ahmedabad 382 210, India
Imported and Exclusively Distributed by:
Zydus Philippines, Inc.
Unit Penthouse 1, 19th Floor, Goldloop Tower A,
Escriva Drive, Barangay San Antonio,
Ortigas Center, Pasig City, Philippines
120 x 140 mm
ALENDRONATE SODIUM
ALDREN 70
5 mg, 10 mg and 70 mg
Anti-osteoporosis
FORMULATION:
Each uncoated tablet contain
Alendronate Sodium
5mg (As Alendronic acid)
Alendronate Sodium
10mg (As Alendronic acid)
Alendronate Sodium
70mg (As Alendronic acid)
DESCRIPTION
Alendronate Sodium Tablets contain alendronate sodium
which 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
INDICATIONS
• Treatment and prevention of osteoporosis in
postmenopausal women.
• 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 7.5mg or greater of prednisone and who have
low bone mineral density.
• Treatment of Paget's disease of bone in men and women.
CLINICAL PHARMACOLOGY
Mechanism of Action
Alendronate sodium is a bisphosphonate that binds to bone
hydroxyapatite and specifically inhibits the activity of
osteoclasts, the bone-resorbingcells. Alendronate sodium
reduces bone resorption with no direct effecton bone
formation. Histomorphometry in baboons and rats showed
that alendronate sodium 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.
Pharmacokinetics
Relative to an intravenous (IV) reference dose, the mean oral
bioavailability of alendronate sodium 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.
Bioavailability was decreased (by approximately 40%) when
10 mg alendronate sodium was administered either 0.5 or 1
hour before a standardized breakfast,when compared to
dosing 2 hours before eating. Bioavailability was negligible
whether alendronate sodium was administered with or up to
twohours after a standardized breakfast. Alendronate sodium
transiently distributesto soft tissues following 1 mg/kg IV
administration but is then rapidly redistributed to bone or
excreted in the urine. The meansteady-state volume of
distribution, exclusive of bone, is at least 28 L in humans.
Protein binding in human plasma is approximately 78%. There
is no evidence that alendronate sodium is metabolized in
Black
animals or humans. Following a single IV dose of [14C]
alendronate sodium, approximately 50% of the radioactivity
was excreted in the urine within 72 hours and little or no
radioactivity was recovered in the feces. The terminal half-life
in humans is estimated to exceed 10 years, probably reflecting
release of alendronate sodium from the skeleton.
DOSAGE AND ADMINISTRATION
Alendronate sodium Tablets must be taken at least one-half
hour before the first food, beverage, or medication of the day
with plain water only. Other beverages (including mineral
water), food, and some medications are likely to reduce the
absorption of alendronate sodium. Waiting less than 30
minutes, or taking alendronte sodium tablets with food,
beverages (other than plain water) or other medication will
lessen the effect of alendronate sodium by decreasing its
absorption into the body. To facilitate delivery to the stomach
and thus reduce the potential for esophageal irritation,
alendronate sodium tablets should only be swallowed upon
arising for the day with a full glass of water (6-8 oz) and
patients should not lie down for at least 30 minutes and until
after their first food of the day. Alendronate sodium Tablets
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. Patients should receive
supplemental calcium and vitamin D, if dietary intake is
inadequate. No dosage adjustment is necessary for the elderly
or for patients with mild-to-moderate renal insufficiency
(creatinine clearance 35 to 60 mL/min). Alendronate sodium
Tablets are not recommended for patients with more severe
renal insufficiency (creatinine clearance < 35 mL/min) due to
lack of experience.
Treatment of osteoporosis in postmenopausal women:
The recommended dosage is:
* one 70 mg tablet once weekly or
* one 10 mg tablet once daily
Treatment to increase bone mass in men with
osteoporosis:
The recommended dosage is one 10 mg tablet once daily.
Prevention of osteoporosis in postmenopausal women:
The recommended dosage is:
* one 35mg tablet once weekly or
* one 5 mg tablet once daily
Treatment of glucocorticoid-induced osteoporosis in
men and women:
The recommended dosage is one 5mg 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 40mg once a day for
six months.
CONTRAINDICATIONS
Alendronate sodium Tablets are contraindicated in the
following settings:
• Abnormalities of the esophagus which delay esophageal
emptying such as stricture or achalasia.
• Inability to stand or sit upright for at least 30 minutes.
• Hypersensitivity to any component of this product.
• Hypocalcemia.
ADVERSE REACTIONS
In clinical studies of up to five years in duration adverse
experiences associated with alendronate sodium usually were
mild, and generally did not require discontinuation of therapy.
The most commonly reported adverse effects reported with
alendronate sodium therapy include the following:
Gastrointestinal: abdominal pain, nausea, dyspepsia,
constipation, diarrhea, flatulence, acid regurgitation,
esophageal ulcer, vomiting, dysphagia, abdominal distention,
gastritis, gastric ulcer, melena.
Musculoskeletal: musculoskeletal (bone, muscle or joint) pain,
muscle cramps.
Nervous System/Psychiatric: headache, dizziness.
Special Senses: taste perversion
PRECAUTIONS AND WARNINGS
Alendronate sodium, 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,
have been reported in patients receiving treatment with
alendronate sodium. Patients should be instructed to
discontinue alendronate sodium tablets 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 alendronate sodium and/or
who fail to swallow it with a full glass (6-8 oz) of water, and/or
who continue to take alendronate sodium after developing
symptoms suggestive of esophageal irritation. Because of
possible irritant effects of alendronate sodium on the upper
gastrointestinal mucosa and a potential for worsening of the
underlying disease, caution should be used when alendronate
sodium tablets are given to patients with active upper
gastrointestinal problems (such as dysphagia, esophageal
diseases, gastritis, duodenitis, or ulcers). Hypocalcemia must
be corrected before initiating therapy with alendronate
sodium. Other disturbances of mineral metabolism (such as
vitamin D deficiency) should also be effectively treated.
Presumably due to the effects of alendronate sodium 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. Alendronate sodium
tablets are not recommended for patients with renal
insufficiency (creatinine clearance < 35 mL/min).
Pregnancy, Lactation & Children
Since there are no studies in pregnant women, alendronate
sodium should be used during pregnancy only if the potential
benefit justifies the potential risk to the mother and fetus. It is
not known whether alendronate sodium is excreted in human
milk. Because many drugs are excreted in human milk, caution
should be exercised when alendronate sodium is
administered to nursing women. Safety and effectiveness of