ALENDRONATE SODIUM tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ALENDRONATE SODIUM (UNII: 2UY4M2U3RA) (ALENDRONIC ACID - UNII:X1J18R4W8P)

Available from:

Amneal Pharmaceuticals of New York LLC

INN (International Name):

ALENDRONATE SODIUM

Composition:

ALENDRONIC ACID 5 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Alendronate sodium tablets are indicated for the treatment of osteoporosis in postmenopausal women. In postmenopausal women, alendronate sodium tablets increase bone mass and reduces the incidence of fractures, including those of the hip and spine (vertebral compression fractures) [see Clinical Studies (14.1) ]. Alendronate sodium tablets are indicated for the prevention of postmenopausal osteoporosis [see Clinical Studies (14.2) ]. Alendronate sodium tablets are indicated for treatment to increase bone mass in men with osteoporosis [see Clinical Studies (14.3) ]. Alendronate sodium tablets are indicated for the 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 Clinical Studies (14.4) ]. Alendronate sodium tablets are indicated for the treatment of Paget's disease of bone in men and women. Treatment is indicated in patients with Paget's disease of bone who have 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 [see Clinical Studies (14.5) ]. The optimal duration of use has not been determined. The safety and effectiveness of alendronate sodium tablets for the treatment of osteoporosis are based on clinical data of four years duration. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture re-evaluated periodically. Alendronate sodium tablets are contraindicated in patients with the following conditions: - Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia [see Warnings and Precautions (5.1) ] - Inability to stand or sit upright for at least 30 minutes [see Dosage and Administration (2.6); Warnings and Precautions (5.1) ] - Hypocalcemia [see Warnings and Precautions (5.2) ] - Hypersensitivity to any component of this product. Hypersensitivity reactions including urticaria and angioedema have been reported [see Adverse Reactions (6.2) ]. Risk Summary Available data on the use of alendronate sodium in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue alendronate sodium when pregnancy is recognized. In animal reproduction studies, daily oral administration of alendronate to rats from before mating through the end of gestation or lactation showed decreased postimplantation survival and decreased pup body weight gain starting at doses equivalent to less than half of the highest recommended 40 mg clinical daily dose (based on body surface area, mg/m2 ). Oral administration of alendronate to rats during organogenesis resulted in reduced fetal ossification starting at doses 3 times the 40 mg clinical daily dose. No similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at doses equivalent to approximately 10 times the 40 mg clinical daily dose. Delayed or failed delivery of offspring, protracted parturition, and late pregnancy maternal and fetal deaths due to maternal hypocalcemia occurred in rats at oral doses as low as one tenth the 40 mg clinical daily dose (see Data) . 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 available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. Consequently, based on the mechanism of action of bisphosphonates, there is a potential 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. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Reproduction studies in rats dosed orally from before mating to the end of gestation or lactation showed decreased postimplantation survival starting at 2 mg/kg/day and decreased body weight gain starting at 1 mg/kg/day, doses equivalent to less than half the 40 mg clinical daily dose based on body surface area, mg/m2 . Incidence of incomplete fetal ossification in vertebral, skull, and sternebral bones were increased in rats dosed orally during organogenesis starting at 10 mg/kg/day (approximately 3 times the 40 mg clinical daily dose). No similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at up to 35 mg/kg/day (equivalent to approximately 10 times the 40 mg clinical daily dose). Both total and ionized calcium decreased in pregnant rats dosed orally with 15 mg/kg/day alendronate (approximately 4 times the 40 mg clinical daily dose) resulting in delays and failures of delivery. Protracted parturition due to maternal hypocalcemia was observed when rats were treated from before mating through gestation starting at 0.5 mg/kg/day (approximately one tenth the 40 mg clinical daily dose). Maternotoxicity (late pregnancy deaths) also occurred in female rats treated orally with 15 mg/kg/day (approximately 4 times the 40 mg clinical daily dose) for varying gestational time periods. These maternal deaths were lessened but not eliminated by cessation of treatment. Calcium supplementation in the drinking water or by subcutaneous minipump to rats dosed orally with 15 mg/kg/day alendronate could not ameliorate the hypocalcemia or prevent the dystocia-related maternal and neonatal deaths. However, intravenous calcium supplementation prevented maternal, but not neonatal deaths. Risk Summary It is not known whether alendronate sodium is present in human breast milk, affects human milk production, or has effects on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for alendronate sodium and any potential adverse effects on the breastfed child from alendronate or from the underlying maternal condition. Alendronate sodium is not indicated for use in pediatric patients. The safety and efficacy of alendronate sodium were examined in a randomized, double-blind, placebo-controlled two-year study of 139 pediatric patients, aged 4 to 18 years, with severe osteogenesis imperfect (OI). One-hundred-and-nine patients were randomized to 5 mg alendronate, the free acid daily (weight less than 40 kg) or 10 mg alendronate, the free acid 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 alendronate sodium-treated patients and 0.1 in the placebo-treated patients. Treatment with alendronate sodium did not reduce the risk of fracture. Sixteen percent of the alendronate sodium 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 alendronate sodium-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 alendronate sodium and placebo groups in reduction of bone pain. The oral bioavailability in children was similar to that observed in adults. The overall safety profile of alendronate sodium in osteogenesis imperfecta patients treated for up to 24 months was generally similar to that of adults with osteoporosis treated with alendronate sodium. However, there was an increased occurrence of vomiting in osteogenesis imperfecta patients treated with alendronate sodium compared to placebo. During the 24-month treatment period, vomiting was observed in 32 of 109 (29.4%) patients treated with alendronate sodium and 3 of 30 (10%) patients treated with placebo. In a pharmacokinetic study, 6 of 24 pediatric osteogenesis imperfecta patients who received a single oral dose of alendronate, the free acid 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 alendronate sodium [see Adverse Reactions (6.2) ]. Of the patients receiving alendronate sodium 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 alendronate sodium 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 Studies (14.1), (14.3), (14.4), (14.5) ], 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. Alendronate sodium is not recommended for patients with creatinine clearance less than 35 mL/min. No dosage adjustment is necessary in patients with creatinine clearance values between 35 to 60 mL/min [see Clinical Pharmacology (12.3) ]. As there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic impairment. No dosage adjustment is necessary [see Clinical Pharmacology (12.3) ].

Product summary:

Alendronate Sodium Tablets USP, for oral administration, are available as: 5 mg – white to off-white, round, flat-faced beveled-edge, unscored tablet debossed with “93” on one side and “5140” on the other side. They are available as follows: Bottles of 30:                NDC 0115-1676-08 Bottles of 100:                NDC 0115-1676-01 10 mg – white to off-white, round, convex, unscored tablet debossed with “93” on one side and “5141” on the other side. They are available as follows: Bottles of 30:               NDC 0115-1678-08 Bottles of 100:               NDC 0115-1678-01 35 mg – white to off-white, pillow-shaped, convex, unscored tablet debossed with “93” on one side and “5172” on the other side. They are available as follows: Cartons of 4:               NDC 0115-1679-34 Cartons of 12 (3 x 4):    NDC 0115-1679-26 40 mg – white to off-white, oval, convex, unscored tablet debossed with “93” on one side and “5142” on the other side. They are available as follows: Bottles of 30:            NDC 0115-1680-08 70 mg – white to off-white, pillow-shaped, convex, unscored tablet debossed with “93” on one side and “5171” on the other side. They are available as follows: Cartons of 4:               NDC 0115-1681-34 Cartons of 12 (3 x 4):    NDC 0115-1681-26 Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). KEEP THIS AND ALL OTHER MEDICATIONS OUT OF THE REACH OF CHILDREN.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Amneal Pharmaceuticals of New York LLC
----------
MEDICATION GUIDE
ALENDRONATE SODIUM (a len’ droe nate soe’ dee um) TABLETS, USP
Read the Medication Guide that comes with alendronate sodium tablets
before you start taking them and
each time you get a refill. There may be new information. This
Medication Guide does not take the place
of talking with your doctor about your medical condition or treatment.
Talk to your doctor if you have
any questions about alendronate sodium tablets.
What is the most important information I should know about alendronate
sodium tablets?
Alendronate sodium tablets can cause serious side effects including:
1.
Esophagus problems
2.
Low calcium levels in your blood (hypocalcemia)
3.
Bone, joint, or muscle pain
4.
Severe jaw bone problems (osteonecrosis)
5.
Unusual thigh bone fractures
1. Esophagus problems.
Some people who take alendronate sodium tablets may develop problems
in the esophagus (the tube that
connects the mouth and the stomach). These problems include
irritation, inflammation, or ulcers of the
esophagus which may sometimes bleed.
•
It is important that you take alendronate sodium tablets exactly as
prescribed to help lower your
chance of getting esophagus problems. (See the section “How should I
take alendronate sodium
tablets?”)
•
Stop taking alendronate sodium tablets and call your doctor right away
if you get chest pain, new
or worsening heartburn, or have trouble or pain when you swallow.
2. Low calcium levels in your blood (hypocalcemia).
Alendronate sodium tablets may lower the calcium levels in your blood.
If you have low blood calcium
before you start taking alendronate sodium tablets, it may get worse
during treatment. Your low blood
calcium must be treated before you take alendronate sodium tablets.
Most people with low blood calcium
levels do not have symptoms, but some people may have symptoms. Call
your doctor right away if you
have symptoms of low blood calcium such as:
•
Spasms, twitches, or cramps in your muscles
•
Numbness or tingling in yo

Summary of Product characteristics

ALENDRONATE SODIUM- ALENDRONATE SODIUM TABLET
AMNEAL PHARMACEUTICALS OF NEW YORK LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ALENDRONATE SODIUM
TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
ALENDRONATE SODIUM
TABLETS.
ALENDRONATE SODIUM TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1995
INDICATIONS AND USAGE
Alendronate sodium tablets are a bisphosphonate indicated for:
Treatment and prevention of osteoporosis in postmenopausal women (1.1,
1.2)
Treatment to increase bone mass in men with osteoporosis (1.3)
Treatment of glucocorticoid-induced osteoporosis (1.4)
Treatment of Paget's disease of bone (1.5)
Limitations of use:
Optimal duration of use has not been determined. For patients at
low-risk for fracture, consider drug
discontinuation after 3 to 5 years of use. (1.6)
DOSAGE AND ADMINISTRATION
Treatment of osteoporosis in postmenopausal women and in men: 10 mg
daily or 70 mg (tablet) once
weekly. (2.1, 2.3)
Prevention of osteoporosis in postmenopausal women: 5 mg daily or 35
mg once weekly. (2.2)
Glucocorticoid-induced osteoporosis: 5 mg daily; or 10 mg daily in
postmenopausal women not
receiving estrogen. (2.4)
Paget's disease: 40 mg daily for six months. (2.5)
Instruct patients to: (2.6)
Swallow tablets whole with 6 to 8 ounces plain water at least 30
minutes before the first food, drink,
or medication of the day.
Not lie down for at least 30 minutes after taking alendronate sodium
tablets and until after food.
DOSAGE FORMS AND STRENGTHS
5 mg, 10 mg, 35 mg, 40 mg and 70 mg tablets (3)
CONTRAINDICATIONS
Abnormalities of the esophagus which delay emptying such as stricture
or achalasia (4, 5.1)
Inability to stand/sit upright for at least 30 minutes (2.6, 4, 5.1)
Hypocalcemia (4, 5.2)
Hypersensitivity to any component of this product (4, 6.2)
WARNINGS AND PRECAUTIONS
_Upper Gastrointestinal Adverse Reactions_ can occur. Instruct
patients to follow dosing instructions.
Discontinue if new or worsening symptoms occur. (