Brand names: Fosamax, Binosto
Drug class: Bone Resorption Inhibitors
- Bone Resorption Inhibitors
- Bisphosphonates
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

Medically reviewed by Drugs.com on Mar 4, 2024. Written by ASHP.

Introduction

Synthetic bisphosphonate; bone resorption inhibitor.

Uses for Alendronate

Osteoporosis

Prevention of osteoporosis in postmenopausal women. Risk factors for postmenopausal osteoporosis and related fractures include early menopause, advanced age, low bone mineral density (BMD), low body mass index (BMI), previous fracture or family history of fracture/osteoporosis, excessive alcohol intake, smoking, inadequate physical activity, low calcium and vitamin D intake, certain drugs (e.g., glucocorticoids), and medical conditions or diseases (e.g., rheumatoid arthritis, diabetes mellitus, Cushing syndrome, hyperparathyroidism).

Used alone or in fixed combination with cholecalciferol (vitamin D₃) for treatment of osteoporosis in postmenopausal women.

Used alone or in fixed combination with cholecalciferol to increase bone mass in men with osteoporosis.

In addition to adequate intake of calcium/vitamin D and other lifestyle modifications (e.g., exercise, avoidance of excessive alcohol and tobacco use), experts recommend that pharmacologic therapy for osteoporosis be considered in postmenopausal women and men (≥50 years of age) with previous hip or vertebral fractures or low BMD; pharmacologic therapy also may be considered in postmenopausal women and men (≥50 years of age) with low bone mass, although there is less evidence supporting overall fracture risk reduction in such patients.

Use of a drug with proven efficacy in reducing fracture risk is recommended; bisphosphonates (e.g., alendronate, risedronate, zoledronic acid, ibandronate) are recommended as one of several first-line drugs.

Individualize choice of therapy based on potential benefits (with respect to fracture risk reduction) and adverse effects of therapy, patient preferences, comorbidities, and risk factors.

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

Alendronate has been used concomitantly with hormone replacement therapy (HRT) in postmenopausal women.

Glucocorticoid-induced Osteoporosis

Treatment of glucocorticoid-induced osteoporosis in men or women receiving glucocorticoids at a daily dosage equivalent to ≥7.5 mg of prednisone who have low BMD. Risks versus benefits in patients receiving a lower dosage of glucocorticoids not established.

Also used for prevention of glucocorticoid-induced osteoporosis^{† [off-label]}.

American College of Rheumatology (ACR) recommends optimizing calcium and vitamin D intake and lifestyle modifications (e.g., diet, smoking cessation, weight-bearing or resistance-training exercise) in all patients receiving long-term glucocorticoid therapy; in addition, pharmacologic therapy with an oral bisphosphonate is recommended in patients who are considered to be at moderate-to-high risk of fracture. Oral bisphosphonates are preferred because of their demonstrated antifracture benefits, safety, and low cost.

Paget Disease of Bone

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

Alendronate Dosage and Administration

General

• Supplemental calcium and vitamin D recommended if daily dietary intake is inadequate.

• 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. (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.

Oral Administration (Alendronate and Alendronate/Cholecalciferol)

Administer alendronate orally as tablets or oral solution.

Administer alendronate/cholecalciferol orally as tablets.

Administer tablets 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. (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.

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

Avoid administering at bedtime or before arising for the day.

Do not suck or chew tablets; potential oropharyngeal irritation.

Avoid any other medications, including calcium supplements or antacids, for 30 minutes after alendronate is administered. (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. Do not take 2 tablets on the same day.

Dosage

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

Adults

Osteoporosis

Prevention of Postmenopausal Osteoporosis

Oral

Alendronate 5 mg once daily (as a tablet) or 35 mg once weekly (as a tablet).

Treatment of Osteoporosis

Oral

Alendronate 10 mg once daily (as a tablet) or 70 mg once weekly (as a tablet or oral solution) in men and postmenopausal women.

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

Optimal duration of treatment not established. Safety and efficacy based on data over 4 years. Reevaluate need for continued therapy periodically in all patients receiving bisphosphonates. Consider discontinuance of bisphosphonate therapy after 3–5 years in patients at low risk of fracture. Evaluate fracture risk periodically in patients who discontinue therapy.

Glucocorticoid-induced Osteoporosis

Prevention† [off-label]

Oral

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

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

Treatment

Oral

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

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

Manufacturer recommends measurement of BMD prior to initiation of therapy; repeat after 6–12 months.

Before initiating therapy in patients receiving long-term glucocorticoid therapy, manufacturer recommends measuring gonadal hormone status; consider replacement therapy, if appropriate.

Paget Disease of Bone

Oral

Alendronate 40 mg once daily for 6 months.

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.

Special Populations

Renal Impairment

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

Geriatric Patients

No dosage adjustment required.

Cautions for Alendronate

Contraindications

• Esophageal abnormalities that delay esophageal emptying (e.g., stricture, achalasia).

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

• Inability to stand or sit upright for at least 30 minutes.

• Hypocalcemia.

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

Warnings/Precautions

Upper GI Effects

Possible severe adverse esophageal effects (e.g., esophagitis, esophageal ulcers, erosions, strictures, perforation). Monitor for any manifestations and discontinue if dysphagia, odynophagia, new or worsening heartburn, or retrosternal pain occurs.

Risk is greater in patients who do not drink 180–240 mL of water with oral bisphosphonates, do not avoid lying down for ≥30 minutes following oral administration, and/or continue to take the drugs after developing symptoms suggesting esophageal irritation; instruct patients carefully about proper administration.

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

Metabolic Effects

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

Correct hypocalcemia and other disorders affecting mineral metabolism (e.g., vitamin D deficiency) before initiation of alendronate therapy; administer supplemental calcium and vitamin D if daily dietary intake is inadequate. Monitor serum calcium and monitor for symptoms of hypocalcemia during therapy.

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). 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.

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). Monitor urine and serum calcium in these patients.

Osteonecrosis of the Jaw

Osteonecrosis and osteomyelitis of the jaw reported in patients receiving bisphosphonates. Mostly associated with tooth extraction and/or local infection with delayed healing. Known risk factors include cancer, concomitant therapies (e.g., chemotherapy, glucocorticoids, angiogenesis inhibitors), poor oral hygiene, preexisting dental disease, anemia, coagulopathy, infection, and ill-fitting dentures. Risk also may increase with increased duration of bisphosphonate use.

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

In patients requiring dental procedures, discontinuance of therapy prior to procedure may reduce the risk of osteonecrosis of the jaw. Base management of patients requiring dental treatment on an individual assessment of risks and benefits.

Musculoskeletal Pain

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

Atypical Fracture of the Femur

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. Often occurs with minimal or no trauma, and may be bilateral. Causality not established; atypical fractures also occur in osteoporotic patients not receiving bisphosphonates. Risk may be increased with concomitant use of glucocorticoid, estrogen, and proton-pump inhibitor therapy.

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

Atrial Fibrillation

Although data are conflicting, possible increased risk of atrial fibrillation with use of bisphosphonates. 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. FDA is continuing to monitor this safety concern.

Use of Fixed Combinations

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

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. However, because of conflicting data, additional study needed to confirm such findings.

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.

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

Specific Populations

Pregnancy

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

Lactation

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

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. Manufacturer states that alendronate not indicated in children.

Geriatric Use

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

Hepatic Impairment

Not evaluated in patients with hepatic impairment.

Renal Impairment

Use not recommended in patients with severe renal impairment (Cl_cr <35 mL/minute). (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

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

Drug Interactions

Antacids or Mineral Supplements Containing Divalent Cations

Potential decreased alendronate absorption when administered with antacids, mineral supplements, or oral drugs containing multivalent cations (e.g., calcium).

Other Oral Medications

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

Specific Drugs

Alendronate Pharmacokinetics

Absorption

Bioavailability

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

Bioavailability of alendronate sodium tablets and oral solution equivalent.

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

Onset

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

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. Bioavailability is negligible whether administered with or up to 2 hours after a meal.

Distribution

Extent

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

Plasma Protein Binding

Alendronate: Approximately 78%.

Elimination

Metabolism

No evidence of metabolism of alendronate.

Elimination Route

Urinary excretion is the sole means of elimination of alendronate.

Half-life

Terminal half-life of alendronate >10 years, reflecting release from bone.

Special Populations

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

Stability

Storage

Oral

Tablets

Alendronate: Tight containers at 15–30°C.

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

Oral Solution

Alendronate: 15–30°C. Do not freeze.

Actions

• Alendronate incorporates into bone and selectively inhibits osteoclast-mediated bone resorption in a dose-dependent manner.

• Alendronate increases bone mineral density.

• Pharmacologically inactive while incorporated into bone matrix. Continuous administration required for activity.

Advice to Patients

• Importance of providing a copy of the manufacturer’s patient information.

• 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).

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

• 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.

• 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).

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

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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