No

Bisphosphonate Derivative

Treatment of osteoporosis in postmenopausal women, Paget's disease of the bone; treatment of glucocorticoid-induced osteoporosis in males and females with low bone mineral density who are receiving a daily dosage greater than or equal to 7.5 mg of prednisone (or equivalent)

C

Hypersensitivity to bisphosphonates or any component of the product; 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

Use caution in patients with renal impairment; hypocalcemia must be corrected before therapy initiation with alendronate; ensure adequate calcium and vitamin D intake to provide for enhanced needs in patients with Paget's disease in whom the pretreatment rate of bone turnover may be greatly elevated.

Note: Incidence of adverse effects increases significantly in patients treated for Paget's disease at 40 mg/day, mostly GI adverse effects

Central nervous system: Headache (2.6%); pain (4.1%)

Gastrointestinal: Flatulence (2.6%); acid regurgitation (2%); esophagitis ulcer (1.5%); dysphagia, abdominal distention (1%)

<1%: Rash, erythema (rare), gastritis (0.5%)

Symptoms of overdose include hypocalcemia, hypophosphatemia; upper GI adverse events (upset stomach, heartburn, esophagitis, gastritis or ulcer)

Treat with milk or antacids to bind alendronate; dialysis would not be beneficial

Ranitidine (by increasing gastric pH) can double the bioavailability of alendronate

A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption direction, leading to an indirect decrease in bone formation

Absorption: Oral: Male: 0.6% given in a fasting state; Female: 0.7%

Protein binding: ~78%

Metabolism: Not metabolized

Bioavailability: Reduced up to 60% with food or drink

Half-life: Terminal: Exceeds 10 years; serum concentrations cleared >95% in 6 hours

Elimination: Renal with unabsorbed drug eliminated in feces

Oral: Alendronate must be taken with plain water first thing in the morning and greater than or equal to 30 minutes before the first food, beverage, or other medication of the day. Patients should be instructed to take alendronate with a full glass of water (6-8 oz) and not lie down for at least 30 minutes to improve alendronate absorption.

Osteoporosis in postmenopausal women:

Prophylaxis: 5 mg once daily

Treatment: 10 mg once daily

Paget's disease of bone: 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.

Treatment of glucocorticoid-induced osteoporosis: 5 mg once daily. A dose of 10 mg once daily should be used in postmenopausal women who are not receiving estrogen. Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.

Elderly: No dosage adjustment is necessary

Dosage adjustment in renal impairment:

Cl_cr 30-60 mL/minute: None necessary

Cl_cr <35 mL/minute: Alendronate is not recommended due to lack of experience

Dosage adjustment in hepatic impairment: None necessary

Ensure adequate calcium and vitamin D intake to provide for enhanced needs in patients with Paget's disease in whom the pretreatment rate of bone turnover may be greatly elevated.

Alkaline phosphatase should be periodically measured; serum calcium, phosphorus, and possibly potassium due to its drug class; use of absorptiometry may assist in noting benefit in osteoporosis; monitor pain and fracture rate

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)

None reported

None reported

No information available to require special precautions

No effects or complications reported

Take as directed, with a full glass of water. Stay in sitting or standing position for 30 minutes following administration to reduce potential for esophageal irritation. Avoid aspirin- or aspirin-containing medications. Consult prescriber to determine necessity of lifestyle changes or dietary supplements of calcium or dietary vitamin D. You may experience GI upset (eg, flatulence, bloating, nausea, acid regurgitation); small frequent meals may help. Report acute headache or gastric pain, unresolved GI upset, or acid stomach. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

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) and not to lie down (stay fully upright sitting or standing) for at least 30 minutes following administration 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 alcohol consumption if these factors exist.

Tablet, as sodium: 5 mg, 10 mg, 40 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.

Watts NB, "Treatment of Osteoporosis With Bisphosphonates," Rheum Dis Clin North Am, 1994, 20(3):717-34.