Generic Name: Alendronate Sodium
Class: Bone Resorption Inhibitors
VA Class: HS900
Chemical Name: (4-Amino-1-hydroxybutylidene)bis-phosphonic acid, monosodium salt, trihydrate
Molecular Formula: C4H13NO7P2•3H2O•Na
CAS Number: 121268-17-5

Introduction

Synthetic bisphosphonate; bone resorption inhibitor.1 2 3 4 112

Uses for Fosamax

Osteoporosis

Prevention of osteoporosis in postmenopausal women1 24 25 with risk factors for development of osteoporosis.1 41 46 47 50 51 52 53 62 Risk factors include premature ovarian failure; family history of osteoporosis; small, slim body frame; endocrine disorders (e.g., thyrotoxicosis, hyperparathyroidism, Cushing’s syndrome, hyperprolactinemia, insulin-dependent diabetes mellitus); cigarette smoking; excessive alcohol use; sedentary lifestyle; low body weight; moderately low body mass; low dietary calcium intake; and Caucasian or Asian race.1 41 46 47 50 51 52 53 62

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Used alone or in fixed combination with cholecalciferol (vitamin D3) for treatment of osteoporosis in postmenopausal women.1 2 3 5 6 7 8 10 11 12 13 112

Used alone or in fixed combination with cholecalciferol for treatment of osteoporosis in men.1 66 70 112

Alendronate/cholecalciferol fixed combination is not recommended for treatment of vitamin D deficiency.112 116

Alendronate has been used concomitantly with hormone replacement therapy.1 68 69

Corticosteroid-induced Osteoporosis

Treatment of corticosteroid-induced osteoporosis in men or women receiving corticosteroids (daily dosage equivalent to ≥7.5 mg of prednisone) who have low bone mineral density.1 57 58 73 78 110

Also used for prevention of corticosteroid-induced osteoporosis.57 58 73 78 110

The American College of Rheumatology (ACR) currently recommends use of one of several bisphosphonates (i.e., alendronate, risedronate, or zoledronic acid) in conjunction with lifestyle modification and calcium and vitamin D supplementation for the prevention and treatment of corticosteroid-induced osteoporosis in select postmenopausal women and men ≥50 years of age who are initiating or currently receiving corticosteroid therapy.110

ACR recommendations based on a risk-stratification approach in which an individual’s clinical risk for developing a fracture is determined based on variables such as gender, age, race/ethnicity, and femoral neck density111 and the individual’s preexisting or anticipated corticosteroid dosage.110

ACR states that because of limited data, use of bisphosphonates for prevention or treatment of corticosteroid-induced osteoporosis in premenopausal women and men <50 years of age can be recommended only in those who have a history of fragility fracture.110

Paget’s Disease of Bone

Treatment of moderate to severe Paget’s disease of bone (osteitis deformans) in patients with serum alkaline phosphatase concentrations ≥ twice ULN or who are symptomatic or at risk for future complications.1 15

Fosamax Dosage and Administration

General

  • Use adjunctively with other measures (e.g., diet, weight-bearing exercise, physical therapy, reduction in smoking, alcohol use) to retard further bone loss.1 41 45 78 112 116

  • Supplemental calcium and vitamin D recommended if daily dietary intake is inadequate, particularly in patients with Paget’s disease of bone or receiving corticosteroids.1 112 116

  • Supplemental vitamin D recommended in patients at increased risk for vitamin D insufficiency (e.g., >70 years of age, nursing home bound, chronically ill, with GI malabsorption syndrome) if necessary.112 (See Metabolic Effects under Cautions.)

  • Recommended intake of vitamin D is 400–800 units daily; once-weekly dose of alendronate/cholecalciferol fixed-combination preparation containing cholecalciferol 2800 or 5600 units provides the equivalent of 400 or 800 units, respectively, of vitamin D daily.112

Administration

Oral Administration (Alendronate and Alendronate/Cholecalciferol)

Administer tablet orally upon arising with a full glass (180–240 mL) of plain water at least 30 minutes before first food, beverage, or other orally administered drug of the day.1 112 (See Food under Pharmacokinetics.)

Drink at least 60 mL (2 oz., a quarter of a cup) of water after taking the oral solution to facilitate gastric emptying.1

Administer in an upright position (sitting or standing).1 112 Avoid lying down for at least 30 minutes following administration and until after the first food of the day.1 112 (See Upper GI Effects under Cautions.)

Avoid administering at bedtime or before arising for the day.1 20 112

Do not suck or chew tablets; potential oropharyngeal irritation.20 1 112 116

Avoid any other medications, including calcium supplements or antacids, for 30 minutes after alendronate is administered.1 112 (See Antacids or Mineral Supplements Containing Divalent Cations under Interactions.)

If a weekly dose is missed, administer missed dose the morning after it is remembered, followed by resumption of the regular weekly schedule.1 112 However, do not take two 70-mg tablets on the same day.1 112

Dosage

Available as alendronate sodium; dosage expressed in terms of alendronate.1 112

Adults

Osteoporosis
Prevention of Postmenopausal Osteoporosis
Oral

Alendronate 5 mg once daily or 35 mg once weekly.1

Treatment of Osteoporosis
Oral

Alendronate 10 mg once daily or 70 mg once weekly in men and postmenopausal women.1

Alendronate/cholecalciferol fixed-combination: Usually, alendronate 70 mg and cholecalciferol 5600 units once weekly in men and postmenopausal women.112 Alternatively, alendronate 70 mg and cholecalciferol 2800 units once weekly.112

Optimal duration of treatment not established.89 90 91 Safety and efficacy based on data supporting fracture reduction over 4 years of treatment.89 90 Reevaluate need for continued therapy periodically in all patients receiving bisphosphonates.1 112

Corticosteroid-induced Osteoporosis
Prevention
Oral

Alendronate 5 mg once daily in postmenopausal women receiving hormone replacement therapy (HRT), premenopausal women, and men.73 78

Alendronate 10 mg once daily in postmenopausal women not receiving HRT.78

Continue alendronate as long as patient continues to receive corticosteroid therapy.78

Treatment
Oral

Alendronate 5 mg once daily in postmenopausal women receiving HRT, premenopausal women, and men.1 73 78

Alendronate 10 mg once daily in postmenopausal women not receiving HRT.1 78

Continue alendronate as long as patient continues to receive corticosteroid therapy.78

Paget’s Disease of Bone
Oral

Alendronate 40 mg once daily for 6 months.1

Consider retreatment after a 6-month posttreatment evaluation period if relapse occurs (i.e., increased serum alkaline phosphatase concentration) or if initial treatment failed to normalize serum alkaline phosphatase concentrations.1

Special Populations

Renal Impairment

No dosage adjustment required in patients with mild to moderate impairment (Clcr 35–60 mL/minute); not recommended in patients with severe impairment (Clcr <35 mL/minute).1 112

Geriatric Patients

No dosage adjustment required.112

Cautions for Fosamax

Contraindications

  • Esophageal abnormalities that delay esophageal emptying (e.g., stricture, achalasia).1 20 21 23 112

  • Patients at increased risk of aspiration should not receive alendronate oral solution.1

  • Inability to stand or sit upright for at least 30 minutes.1 20 21 23 112

  • Hypocalcemia.1 112

  • Known hypersensitivity to alendronate or any ingredient in the formulation.1 112

Warnings/Precautions

Warnings

Upper GI Effects

Possible severe adverse esophageal effects (e.g., esophagitis, esophageal ulcers, erosions, strictures, perforation).1 16 18 20 21 23 112 Monitor for any manifestations1 16 18 20 21 23 112 and discontinue if dysphagia, odynophagia, new or worsening heartburn, or retrosternal pain occurs.1 20 23 112

Use with caution in patients with history of upper GI disease (e.g., Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis, ulcers).1 20 23 112 Gastric and duodenal ulcers (some severe and with complications) reported during postmarketing experience.1 112

General Precautions

Diagnosis

Consider other possible causes of osteoporosis before beginning alendronate.1 112

Metabolic Effects

Possible asymptomatic decreases in serum calcium and phosphate concentrations, particularly in patients with Paget’s disease and in those receiving corticosteroids; ensure adequate calcium and vitamin D intake.1 112

Correct hypocalcemia and other disorders affecting mineral metabolism (e.g., vitamin D deficiency) before initiation of alendronate therapy;1 112 administer supplemental calcium and vitamin D if daily dietary intake is inadequate.1 26 27 28 29 38 46 47 48 51 52 53 Monitor serum calcium and monitor for symptoms of hypocalcemia during therapy.112

Fixed combination of alendronate and cholecalciferol (vitamin D3) is not recommended for treatment of vitamin D deficiency (i.e., 25-hydroxyvitamin D concentration <9 ng/mL).112 Patients at risk for vitamin D insufficiency (e.g., GI malabsorption syndromes) may require higher doses of vitamin D supplementation; consider measurement of 25-hydroxyvitamin D.112

Vitamin D3 supplementation may increase risk of hypercalcemia and/or hypercalciuria in patients with diseases associated with unregulated overproduction of 1,25-dihydroxyvitamin D (e.g., leukemia, lymphoma, sarcoidosis).112 Monitor urine and serum calcium in these patients.112

Musculoskeletal Effects

Severe and occasionally incapacitating bone, joint, and/or muscle pain reported infrequently with bisphosphonate therapy.1 84 85 86 Time to onset varied from 1 day to years (mean onset about 3 months) after treatment initiation.1 If severe symptoms occur, discontinue drug.1 Such pain generally improves following discontinuance, but may recur upon subsequent rechallenge with the same drug or another bisphosphonate.1 84 85 86

Osteonecrosis and osteomyelitis of the jaw reported, principally in cancer patients receiving bisphosphonates, usually when given IV.112 117 118 Most cases associated with tooth extraction and/or local infection, often with delayed healing, but some cases occurred in patients with postmenopausal osteoporosis receiving oral therapy.112 117 118 Known risk factors include cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene, preexisting dental disease, anemia, coagulopathy, and infection.112 117

If osteonecrosis of the jaw develops, consult an oral surgeon for treatment.112 117 Dental surgery may exacerbate condition.112 117

In patients requiring dental procedures, no data are available to suggest whether discontinuance of therapy prior to procedure reduces the risk of osteonecrosis of the jaw.112 117 Base management of patients requiring dental treatment on an individual assessment of risks and benefits.112 117

Atypical (subtrochanteric or diaphyseal), low-energy or low-trauma femur fractures reported rarely with long-term use (>3 years) of bisphosphonates, mostly in patients receiving these drugs for osteoporosis.91 93 Often occurs with minimal or no trauma, and may be bilateral.89 90 91 93 Causality not established; atypical fractures also occur in osteoporotic patients not receiving bisphosphonates.91 92 93 94 Risk may be increased with concomitant use of glucocorticoid, estrogen, and proton-pump inhibitor therapy.93 95 96 98

Evaluate patients who present with new thigh or groin pain for possibility of an atypical femoral fracture; include assessment of the contralateral limb.89 90 91 93 94 Consider interruption of bisphosphonate therapy in patients with manifestations of possible femoral fracture; weigh risks versus benefits of continued treatment.89 90 Discontinue if a femoral shaft fracture is confirmed.91 92 93

Atrial Fibrillation

Although data are conflicting, possible increased risk of atrial fibrillation with use of bisphosphonates.106 107 108 FDA analysis of data from long-term (6 months to 3 years) controlled trials identified a higher rate of atrial fibrillation in patients receiving bisphosphonates (alendronate, ibandronate, risedronate, or zoledronic acid) versus placebo; however, only a few events reported in each study.108 FDA is continuing to monitor this safety concern.108

Use of Fixed Combinations

When alendronate is used in fixed combination with cholecalciferol, consider the cautions, precautions, and contraindications associated with cholecalciferol.112 113

Corticosteroid-induced Osteoporosis

Measure bone mineral density at initiation of therapy and after 6–12 months of concomitant use with corticosteroids.1

Potential Risk of Esophageal Cancer

Some evidence (from postmarketing experience and observational studies) suggests a possible association between use of oral bisphosphonates and an increased risk of esophageal cancer.88 100 101 However, because of conflicting data,101 102 103 additional study needed to confirm such findings.100

FDA states that benefits of oral bisphosphonates continue to outweigh their potential risks in patients with osteoporosis; it is important to consider that esophageal cancer is rare, especially in women.100 101

Avoidance of oral bisphosphonates in patients with Barrett’s esophagus, a known precursor to esophageal adenocarcinoma, has been recommended.88

Specific Populations

Pregnancy

Alendronate alone or in fixed combination with cholecalciferol: Category C.1 112

Lactation

Not known whether alendronate is distributed into milk.1 112 Caution if used in nursing women.1 112

Pediatric Use

In randomized trial in pediatric patients (4–18 years of age) with osteogenesis imperfecta, treatment with alendronate did not reduce risk of fracture or bone pain; increased incidence of vomiting in children receiving alendronate compared with placebo.1 112 Manufacturer states that alendronate not indicated in children.1 112

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1 112

Renal Impairment

Decreased clearance of alendronate likely.1 112 Use not recommended in patients with severe renal insufficiency (Clcr <35 mL/minute).1 112

Common Adverse Effects

Abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, musculoskeletal pain, nausea.1 112

Interactions for Fosamax

Antacids or Mineral Supplements Containing Divalent Cations

Potential decreased alendronate absorption when administered with divalent cations (e.g., calcium).1 112

Other Oral Medications

Potential decreased alendronate absorption when administered concomitantly with other oral medications.117 Administer alendronate ≥30 minutes prior to other oral medications.117

Specific Drugs

Drug

Interaction

Comments

Antacids (calcium)

May interfere with absorption of alendronate112

Wait ≥30 minutes after taking alendronate before taking any other oral medications112

Hormone replacement therapy (estrogens; estrogens and progestins)

Potential increased effects on bone mineral density1 68 69

NSAIAs (e.g., aspirin)

Aspirin increased GI toxicity in clinical studies; no increase in toxicity with concomitant NSAIAs in one study1 112

Use caution1 112

Prednisone

No change in alendronate bioavailability1 112

Ranitidine

IV ranitidine doubled alendronate bioavailability1 112

Fosamax Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability of alendronate in women and men is 0.64 and 0.59%, respectively.1 112

Bioavailability of alendronate sodium tablets and oral solution equivalent.1

Bioavailability of conventional tablets and fixed-combination tablets containing cholecalciferol (2800 and 5600 units) equivalent.112

Onset

Decrease in bone resorption rate evident as early as 1 month.1 112

Food

Alendronate bioavailability decreased by 40% when administered 0.5–1 hour prior to a meal, and by 60% when administered with coffee or orange juice.1 112 Bioavailability is negligible whether administered with or up to 2 hours after a meal.1 112

Distribution

Extent

Alendronate is widely distributed after oral administration.114 Subsequently, redistributes rapidly to skeletal tissues.112 114 Mean steady-state volume of distribution, exclusive of bone, is ≥28 L.1 112 114

Plasma Protein Binding

Alendronate: Approximately 78%.1 112

Elimination

Metabolism

No evidence of metabolism of alendronate.1 114

Elimination Route

Urinary excretion is the sole means of elimination of alendronate.1 3 112 113

Half-life

Terminal half-life of alendronate >10 years, reflecting release from bone.1 2 3 4 11 112

Special Populations

In patients with renal impairment, clearance of alendronate likely to be reduced.1 112 Somewhat greater accumulation in bone expected.1 112

Stability

Storage

Oral

Tablets

Alendronate: Tight containers at 15–30°C.1

Alendronate/cholecalciferol fixed combination: 20–25°C (may be exposed to 15–30°C).112 Keep tablets in sealed blisters until immediately before use.112 Protect from moisture and light.112

Oral Solution

Alendronate: 15–30°C.1 Do not freeze.1

Actions

  • Alendronate incorporates into bone and selectively inhibits osteoclast-mediated bone resorption in a dose-dependent manner.1 2 3 4 5 8 9 10

  • Alendronate increases bone mineral density.1 8 24 58 66 69 70 72 73 74 78 112

  • Pharmacologically inactive while incorporated into bone matrix.1 2 3 4 11 112 Continuous administration required for activity.1 2 3 4 11 112

Advice to Patients

  • Importance of providing a copy of the manufacturer’s patient information.1 17 20 21 23 112

  • Importance of correct administration (e.g., avoiding foods and beverages other than plain water, not lying down for ≥30 minutes following administration, avoiding administering at bedtime or before arising for the day).1 20 112 116

  • Importance of swallowing tablets whole, without chewing or sucking.20 112 116

  • Importance of discontinuing and informing clinician if symptoms of esophageal disease (e.g., difficulty or pain on swallowing; retrosternal, abdominal or esophageal pain; new or worsening heartburn) develop.1 20 23 112 116

  • Importance of adhering to recommended lifestyle modifications (e.g., weight-bearing exercise, calcium and vitamin D consumption, avoidance of excessive cigarette smoking and/or alcohol consumption).1 112 116

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 112

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 112

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Alendronate (Fosamax) for the treatment of Paget’s disease of bone is available only through Paget’s Patient Support Program with Pharma Care Specialty Pharmacy (800-238-7828 ext. 58197) distribution system for the 40-mg dosage regimen.115

Alendronate Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

70 mg/75 mL (of alendronate)

Fosamax

Merck

Tablets

5 mg (of alendronate)

Fosamax

Merck

10 mg (of alendronate)

Fosamax

Merck

35 mg (of alendronate)

Fosamax

Merck

40 mg (of alendronate)

Fosamax

Merck

70 mg (of alendronate)

Fosamax

Merck

Alendronate Sodium and Cholecalciferol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

70 mg (of alendronate) and Cholecalciferol 2800 units

Fosamax Plus D

Merck

70 mg (of alendronate) and Cholecalciferol 5600 units

Fosamax Plus D

Merck

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Alendronate Sodium 10MG Tablets (TEVA PHARMACEUTICALS USA): 100/$240.96 or 300/$679.95

Alendronate Sodium 40MG Tablets (TEVA PHARMACEUTICALS USA): 30/$179.99 or 90/$489.95

Alendronate Sodium 5MG Tablets (TEVA PHARMACEUTICALS USA): 100/$255.98 or 300/$729.91

Alendronate Sodium 70MG Tablets (TEVA PHARMACEUTICALS USA): 4/$13.99 or 12/$20.99

Fosamax 10MG Tablets (MERCK SHARP &amp; DOHME): 30/$95.12 or 90/$262.94

Fosamax 35MG Tablets (MERCK SHARP &amp; DOHME): 4/$87.66 or 12/$252.29

Fosamax 5MG Tablets (MERCK SHARP &amp; DOHME): 30/$91.92 or 90/$265.31

Fosamax 70MG Tablets (MERCK SHARP &amp; DOHME): 4/$101.99 or 12/$288.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 14, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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