Alendronate Sodium

ALENDRONATE SODIUM — alendronate sodium solution
ANI Pharmaceuticals, Inc.

1 INDICATIONS & USAGE

1.1 Treatment of Osteoporosis in Postmenopausal Women

Alendronate sodium is indicated for the treatment of osteoporosis in postmenopausal women. In postmenopausal women, alendronate increases bone mass and reduces the incidence of fractures, including those of the hip and spine (vertebral compression fractures) [see Clinical Studies (14.1)].

1.3 Treatment to Increase Bone Mass in Men with Osteoporosis

Alendronate sodium is indicated for treatment to increase bone mass in men with osteoporosis [see Clinical Studies (14.3)].

1.6 Important Limitations of Use

The optimal duration of use has not been determined. The safety and effectiveness of alendronate 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.

2 DOSAGE & ADMINISTRATION

2.1 Treatment of Osteoporosis in Postmenopausal Women

The recommended dosage is:

• one bottle of 70 mg oral solution once weekly

2.3 Treatment to Increase Bone Mass in Men with Osteoporosis

The recommended dosage is:

• one bottle of 70 mg oral solution once weekly

2.6 Important Administration Instructions

Instruct patients to do the following:

• Take alendronate at least one-half hour before the first food, beverage, or medication of the day with plain water only [see Patient Counseling Information (17.2)]. Other beverages (including mineral water), food, and some medications are likely to reduce the absorption of alendronate [see Drug Interactions (7.1)]. Waiting less than 30 minutes, or taking alendronate with food, beverages (other than plain water) or other medications will lessen the effect of alendronate by decreasing its absorption into the body.
• Take alendronate upon arising for the day. To facilitate gastric emptying alendronate oral solution should be followed by at least 2 ounces (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. Alendronate 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 and Precautions (5.1) and Patient CounselingInformation (17.2)].

2.7 Recommendations for Calcium and Vitamin D Supplementation

Instruct patients to take supplemental calcium if dietary intake is inadequate [see Warnings andPrecautions (5.2)]. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home-bound, or chronically ill) may need vitamin D supplementation. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.

Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.

2.8 Administration Instructions for Missed Doses

If a once-weekly dose of alendronate sodium is missed, instruct patients to 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.

3 DOSAGE FORMS & STRENGTHS

• Alendronate Sodium Oral Solution, 70 mg, is a clear, colorless to pale pink solution with a raspberry flavor, free from visible particulate matter.

4 CONTRAINDICATIONS

Alendronatesodiumiscontraindicatedinpatientswiththefollowing conditions:

• Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia [see Warnings and Precautions(5.1)]
• Inabilitytostandorsituprightforatleast 30 minutes [see Dosage and Administration(2.6);Warnings and Precautions(5.1)]
• Do not administer alendronate sodium oral solution to patients at increased risk of aspiration.
• Hypocalcemia [see Warnings and Precautions(5.2)]
• Hypersensitivity to any component of this product. Hypersensitivity reactions including urticarial and angioedema have been reported [see AdverseReactions(6.2)]

5 WARNINGS AND PRECAUTIONS

5.1 Upper Gastrointestinal Adverse Reactions

Alendronate, like other bisphosphonates administered orally, may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when alendronate is given to patients with active upper gastrointestinal problems (such as known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis, or ulcers).

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 oral bisphosphonates including alendronate. 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 alendronate 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 oral bisphosphonates including alendronate and/or who fail to swallow oral bisphosphonates including alendronate with the recommended full glass (6 to 8 ounces) of water, and/or who continue to take oral bisphosphonates including alendronate 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 (2.6)]. In patients who cannot comply with dosing instructions due to mental disability, therapy with alendronate should be used under appropriate supervision.

There have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications, although no increased risk was observed in controlled clinical trials [see Adverse Reactions (6.2)].

5.2 Mineral Metabolism

Hypocalcemia must be corrected before initiating therapy with alendronate [see Contraindications (4)]. 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 alendronate.

Presumably due to the effects of alendronate 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.

5.3 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 (6.2)]. This category of drugs includes 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 alendronate, the percentages of patients with these symptoms were similar in the alendronate and placebo groups.