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Treatment and prevention of osteoporosis in postmenopausal females; treatment of osteoporosis in males; Paget's disease of the bone in patients who are symptomatic, at risk for future complications, or with alkaline phosphatase 2 times the upper limit of normal; treatment of glucocorticoid-induced osteoporosis in males and females with low bone mineral density who are receiving a daily dosage 7.5 mg of prednisone (or equivalent)
Safety and efficacy have not been established in pregnant women. Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. Based on limited case reports with pamidronate, serum calcium levels in the newborn may be altered if administered during pregnancy.
Excretion in breast milk unknown/use caution
Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; oral solution should not be used in patients at risk of aspiration
Use caution in patients with renal impairment; hypocalcemia must be corrected before therapy initiation; ensure adequate calcium and vitamin D intake. May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition).
Incidence of adverse effects increases significantly in patients treated for Paget's disease at 40 mg/day, mostly GI adverse effects.Note:
>10%: Endocrine & metabolic: Hypocalcemia (transient, mild, 18%); hypophosphatemia (transient, mild, 10%)
1% to 10%:
Central nervous system: Headache (0.2% to 3%)
Gastrointestinal: Abdominal pain (1% to 7%), acid reflux (1% to 5%), dyspepsia (1% to 4%), nausea (1% to 4%), flatulence (0.2% to 4%), diarrhea (0.6% to 3%), constipation (0.3% to 3%), esophageal ulcer (0.1% to 2%), abdominal distension (0.2% to 1%), gastritis (0.2% to 1%), vomiting (0.2% to 1%), dysphagia (0.1% to 1%), gastric ulcer (1%), melena (1%)
Neuromuscular & skeletal: Musculoskeletal pain (0.4% to 4%), muscle cramps (0.2% to 1%)
<1%, postmarketing, and/or case reports: Angioedema; bone, muscle, or joint pain (occasionally severe, considered incapacitating in rare cases); duodenal ulcer, esophageal erosions, esophageal perforation, esophageal stricture, esophagitis, hypersensitivity reactions, hypocalcemia (symptomatic), oropharyngeal ulceration, osteonecrosis, photosensitivity (rare), pruritus, rash, scleritis (rare), Stevens-Johnson syndrome, taste perversion, toxic epidermal necrolysis, urticaria, uveitis (rare)
Symptoms of overdose include hypocalcemia, hypophosphatemia, and upper GI adverse affects (eg, upset stomach, heartburn, esophagitis, gastritis, or ulcer). Treat with milk or antacids to bind alendronate. Dialysis would not be beneficial.
Aspirin: Increased incidence of adverse GI effects when >10 mg alendronate is used in patients taking aspirin-containing products
Oral medications (especially those containing multivalent cations): May interfere with alendronate absorption; wait at least 30 minutes after taking alendronate before taking any oral medications
Ranitidine (by increasing gastric pH) can double the bioavailability of alendronate
Food: All food and beverages interfere with absorption. Coadministration with caffeine may reduce alendronate efficacy. Coadministration with dairy products may decrease alendronate absorption. Beverages (especially orange juice and coffee), food, and medications (eg, antacids, calcium, iron, and multivalent cations) may reduce the absorption of alendronate as much as 60%.
Store tablets and oral solution at room temperature of 15°C to 30°C (59°F to 86°F); keep in well-closed container
A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density. In Paget's disease, characterized by disordered resorption and formation of bone, inhibition of resorption leads to an indirect decrease in bone formation; but the newly-formed bone has a more normal architecture.
Distribution: 28 L (exclusive of bone)
Protein binding: ~78%
Bioavailability: Fasting: Female: 0.7%; Male: 0.6%; reduced 60% with food or drink
Half-life elimination: Exceeds 10 years
Excretion: Urine; feces (as unabsorbed drug)
Oral: Adults: Patients treated with glucocorticoids and those with Paget's disease should receive adequate amounts of calcium and vitamin D.Note:
Osteoporosis in postmenopausal females:
Prophylaxis: 5 mg once daily or 35 mg once weekly
Treatment: 10 mg once daily or 70 mg once weekly
Osteoporosis in males: 10 mg once daily or 70 mg once weekly
Osteoporosis secondary to glucocorticoids in males and females: Treatment: 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen.
Paget's disease of bone in males and females: 40 mg once daily for 6 months
Retreatment: Relapses during the 12 months following therapy occurred in 9% of patients who responded to treatment. Specific retreatment data are not available. Retreatment with alendronate may be considered, following a 6-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.
Elderly: No dosage adjustment is necessary
Dosage adjustment in renal impairment:
Clcr 35-60 mL/minute: None necessary
Clcr<35 mL/minute: Alendronate is not recommended due to lack of experience
Dosage adjustment in hepatic impairment: None necessary
Alendronate must be taken with plain water (tablets 6-8 oz; oral solution 2 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Patients should be instructed to stay upright (not to lie down) for at least 30 minutes until after first food of the day (to reduce esophageal irritation). Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
Alkaline phosphatase should be periodically measured; serum calcium and phosphorus; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging; phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
Ensure adequate calcium and vitamin D intake; however, wait at least 30 minutes after taking alendronate before taking any supplement. Must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed, with a full glass of water first thing in the morning and at least 30 minutes before the first food or beverage of the day. Wait at least 30 minutes after taking alendronate before taking anything else. Stay in sitting or standing position for 30 minutes following administration and until after the first food of the day to reduce potential for esophageal irritation. Consult prescriber to determine necessity of lifestyle changes (eg, decreased smoking, decreased alcohol intake, dietary supplements of calcium or vitamin D). May cause flatulence, bloating, nausea, or acid regurgitation; small, frequent meals may help. Report acute headache or gastric pain, unresolved GI upset, or acid stomach. Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.Pregnancy/breast-feeding precautions:
Patients should be instructed that the expected benefits of alendronate may only be obtained when each tablet is administered with plain water the first thing in the morning and at least 30 minutes before the first food, beverage, or medication of the day. Also instruct them that waiting >30 minutes will improve alendronate absorption. Even dosing with orange juice or coffee markedly reduces the absorption of alendronate.
Patients should be instructed to take alendronate with a full glass of water (6-8 oz/180-240 mL); do not allow patient to lie down (keep patient fully upright sitting or standing) for at least 30 minutes following administration and until after eating the first food of the day to facilitate delivery to the stomach and reduce the potential for esophageal irritation.
Patients should be instructed to take supplemental calcium and vitamin D if dietary intake is inadequate. Consider weight-bearing exercise along with the modification of certain behavioral factors, such as excessive cigarette smoking or ethanol consumption if these factors exist.
No significant effects or complications reported
No information available to require special precautions
Solution, oral, as monosodium trihydrate: 70 mg/75 mL [contains parabens; raspberry flavor]
Tablet, as sodium: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
Chesnut CH 3rd, McClung MR, Ensrud KE, et al, "Alendronate Treatment of the Postmenopausal Osteoporatic Woman: Effect of Multiple Dosages on Bone Mass and Bone Remodeling,"Am J Med, 1995, 99(2):144-52.
French AE, Kaplan N, Lishner M, et al, "Taking Bisphosphonates During Pregnancy,"Can Fam Physician, 2003, 49:1281-2.
Orwoll E, Ettinger M, Weiss S, et al, "Alendronate for the Treatment of Osteoporosis in Men,"N Engl J Med, 2000, 343(9):604-10.
Ruggiero SL, Mehrotra B, Rosenberg TJ, et al, "Osteonecrosis of the Jaws Associated With the Use of Bisphosphonates: A Review of 63 Cases,"J Oral Maxillofac Surg, 2004, 62(5):527-34.
Watts NB, "Treatment of Osteoporosis With Bisphosphonates,"Rheum Dis Clin North Am, 1994, 20(3):717-34.
Fosamax® (CA); Novo-Alendronate (CA)