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
Brands: Fosamax, Fosamax Plus D

Special Alerts:

[Posted 07/21/2011] ISSUE: FDA notified healthcare professionals and patients about its ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of cancer of the esophagus. FDA has not concluded that taking an oral bisphosphonate drug increases the risk of esophageal cancer. There are insufficient data to recommend endoscopic screening of asymptomatic patients. FDA will continue to evaluate all available data supporting the safety and effectiveness of bisphosphonate drugs and will update the public when more information becomes available.

BACKGROUND: Oral bisphosphonates are commonly used for the prevention and treatment of osteoporosis as well as to treat other bone diseases such as Paget’s disease. There have been conflicting findings from studies evaluating the risk of esophageal cancer. Esophagitis and other esophageal events have been reported, particularly in patients who do not follow the specific directions for use of oral bisphosphonates. See the Data Summary in the Drug Safety Communication for additional details at: .

RECOMMENDATION: Patients should talk with their healthcare professional about the benefits and risks of taking oral bisphosphonates and how long they should expect to take them. Patients should talk with their healthcare professional if they develop swallowing difficulties, chest pain, new or worsening heartburn, or have trouble or pain when swallowing. Patients should be instructed to carefully follow the directions for use of the oral bisphosphonate drug they are prescribed. For more information visit the FDA website at: and .

[Posted 10/13/2010] ISSUE: FDA is updating the public regarding information previously communicated describing the risk of atypical fractures of the thigh, known as subtrochanteric and diaphyseal femur fractures, in patients who take bisphosphonates for osteoporosis. This information will be added to the Warnings and Precautions section of the labels approved to treat osteoporosis, including alendronate (Fosamax), alendronate with cholecalciferol (Fosamax Plus D), risedronate (Actonel and Atelvia), risedronate with calcium carbonate (Actonel with Calcium), ibandronate (Boniva), tiludronate (Skelid), and zoledronic acid (Reclast) and their generic products. A Medication Guide will also be required to be given to patients when they pick up their bisphosphonate prescription.

BACKGROUND: Atypical subtrochanteric femur fractures are fractures in the bone just below the hip joint. Diaphyseal femur fractures occur in the long part of the thigh bone. These fractures are very uncommon and appear to account for less than 1% of all hip and femur fractures overall. Although it is not clear if bisphosphonates are the cause, these unusual femur fractures have been predominantly reported in patients taking bisphosphonates.

RECOMMENDATIONS: Patients should continue to take their medication unless told to stop by their healthcare professional. FDA recommends that healthcare professionals should discontinue potent antiresorptive medications (including bisphosphonates) in patients who have evidence of a femoral shaft fracture. For more information visit the FDA website at: and .

[Posted 03/11/2010] FDA notified healthcare professionals and patients that at this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures. FDA is working with outside experts, including members of the recently convened American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather more information and evaluate the issue further.

FDA recommends that healthcare professionals follow the recommendations in the drug label when prescribing oral bisphosphonates.

Patients should continue taking oral bisphosphonates unless told by their healthcare professional to stop. Patients should talk to their healthcare professional if they develop new hip or thigh pain or have any concerns with their medications. For more information visit the FDA website at: and .

[Posted 11/12/2008] FDA issued an update to the Agency’s review of safety data regarding the potential increased risk of atrial fibrillation in patients treated with a bisphosphonate drug. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. FDA reviewed data on 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed for 6 months to 3 years. The occurrence of atrial fibrillation was rare within each study, with most studies containing 2 or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increase rate of atrial fibrillation. Healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication. For more information visit the FDA website at: , and .

REMS:

FDA approved a REMS for alendronate to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Synthetic bisphosphonate; bone resorption inhibitor.^{1 2 3 4 a}

Uses for Alendronate Sodium

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Osteoporosis

Alendronate is used for prevention of osteoporosis in postmenopausal women^{1 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; or Caucasian or Asian race.^{1 41 46 47 50 51 52 53 62}

Alendronate is 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 a}

Alendronate is used alone or in fixed combination with cholecalciferol for treatment of osteoporosis in men.^{1 66 70 a}

Alendronate/cholecalciferol fixed combination is not recommended for treatment of vitamin D deficiency.^{a e}

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

Corticosteroid-induced Osteoporosis

Alendronate is used for treatment of corticosteroid-induced osteoporosis in patients receiving corticosteroids (daily dosage ≥5–7.5 mg of prednisone).^{1 57 58 73 78}

Alendronate is used for prevention of corticosteroid-induced osteoporosis† in patients receiving corticosteroid therapy (daily dosage ≥5 mg of prednisone).^{57 58 73 78}

American College of Rheumatology considers patients receiving ≥5 mg prednisone daily for ≥3 months at risk for bone loss.⁷⁸ Recommends bisphosphonate therapy for all long-term corticosteroid-treated men, premenopausal women (with caution), and postmenopausal women with or without hormone replacement therapy (combined estrogen and progestin therapy).⁷⁸

Paget’s Disease of Bone

Alendronate is used for 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}

Alendronate Sodium 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 a e}

  
  


• 
  

  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 1 a e}

  
  


• 
  

  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.^a (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.^a

  
  

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 1 a} (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 a} Avoid lying down for at least 30 minutes following administration and until after the first food of the day.^{1 a} (See GI Effects under Cautions.)

Avoid administering at bedtime or before arising for the day.^{1 20 a}

Do not suck or chew tablets; potential oropharyngeal irritation.^{20 1 a e}

Avoid any other medications, including calcium supplements or antacids, for 30 minutes after alendronate is administered.^{1 a} (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 a} However, do not take two 70-mg tablets on the same day.^{1 a}

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as alendronate sodium; dosage expressed in terms of alendronate.^{1 a}

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.^a Alternatively, alendronate 70 mg and cholecalciferol 2800 units once weekly.^a

Corticosteroid-induced Osteoporosis

Prevention of Corticosteroid-induced Osteoporosis†

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 of Corticosteroid-induced Osteoporosis

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 (Cl_cr 35–60 mL/minute); not recommended in patients with severe impairment (Cl_cr <35 mL/minute).^{1 a}

Geriatric Patients

No dosage adjustment required.^a

Cautions for Alendronate Sodium

Contraindications

• 
  

  Esophageal abnormalities that delay esophageal emptying (e.g., stricture, achalasia).^{1 20 21 23 a}

  
  


• 
  

  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 a}

  
  


• 
  

  Hypocalcemia.^{1 a}

  
  


• 
  

  Known hypersensitivity to alendronate or any ingredient in the formulation.^{1 a}

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

GI Effects

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

Cautious use recommended in patients with history of upper GI disease (e.g., dysphagia, esophageal diseases, gastritis, duodenitis, ulcers).^{1 20 23 a} Gastric and duodenal ulcers (some severe and with complications) reported in postmarketing surveillance.^{1 a}

General Precautions

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Diagnosis

Consider other possible causes of osteoporosis before beginning alendronate.^{1 a}

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 a}

Correct hypocalcemia and other disorders affecting mineral metabolism (e.g., vitamin D deficiency) before initiation of alendronate therapy;^{1 a} 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.^a

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).^a 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.^a

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).^a Monitor urine and serum calcium in these patients.^a

Musculoskeletal Effects

Severe and occasionally incapacitating bone, joint, and/or muscle pain, especially in postmenopausal women, has been reported in postmarketing surveillance.^{a f} Time to onset varied from 1 day to several months after treatment initiation.^{a f} If severe symptoms occur, discontinue drug.^a Such pain improves following discontinuance, but may recur upon subsequent rechallenge with the same drug or another bisphosphonate.^{a f}

Osteonecrosis of the jaw has been reported principally in cancer patients receiving IV bisphosphonates.^{a f} Most cases were associated with tooth extraction and/or local infection, often with delayed healing, but some cases occurred in patients with postmenopausal osteoporosis receiving oral therapy.^{a f} Known risk factors include cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene, preexisting dental disease, anemia, coagulopathy, and infection.^{a f}

If osteonecrosis of the jaw develops, consult an oral surgeon for treatment.^{a f} Dental surgery may exacerbate condition.^{a f}

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.^{a f} Base management of patients requiring dental treatment on an individual assessment of risks and benefits.^{a f}

Use of Fixed Combinations

When alendronate is used in fixed combination with cholecalciferol, consider the cautions, precautions, and contraindications associated with cholecalciferol.^{a b}

Corticosteroid-induced Osteoporosis

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

Specific Populations

Pregnancy

Alendronate alone or in fixed combination with cholecalciferol: Category C.^{1 a}

Lactation

Not known whether alendronate is distributed into milk.^{1 a} Caution if used in nursing women.^{1 a}

Pediatric Use

Safety and efficacy not established.^{1 a}

Geriatric Use

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

Renal Impairment

Decreased clearance of alendronate likely.^{1 a} Use not recommended in patients with severe renal insufficiency (Cl_cr <35 mL/minute).^{1 a}

Common Adverse Effects

Abdominal pain.^{1 a}

Interactions for Alendronate Sodium

Antacids or Mineral Supplements Containing Divalent Cations

Potential decreased alendronate absorption when administered with divalent cations (e.g., calcium).^{1 a}

Other Oral Medications

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

Specific Drugs

Drug	Interaction	Comments
Antacids (calcium)	May interfere with absorption of alendronatea	Wait at least ≥30 minutes after taking alendronate before taking any other oral medicationsa
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 a	Use caution1 a
Prednisone	No change in alendronate bioavailability1 a
Ranitidine	IV ranitidine doubled alendronate bioavailability1 a

Alendronate Sodium Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability of alendronate in women and men is 0.64 and 0.59%, respectively.^{1 a}

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.^a

Onset

Decrease in bone resorption rate evident as early as 1 month.^{1 a}

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 a} Bioavailability is negligible whether administered with or up to 2 hours after a meal.^{1 a}

Distribution

Extent

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

Plasma Protein Binding

Alendronate: Approximately 78%.^{1 a}

Elimination

Metabolism

No evidence of metabolism of alendronate.^{1 c}

Elimination Route

Urinary excretion is the sole means of elimination of alendronate.^{1 3 a b}

Half-life

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

Special Populations

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

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).^a Keep tablets in sealed blisters until immediately before use.^a Protect from moisture and light.^a

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 a}

  
  


• 
  

  Pharmacologically inactive while incorporated into bone matrix.^{1 2 3 4 11 a} Continuous administration required for activity.^{1 2 3 4 11 a}

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of providing a copy of the manufacturer’s patient information.^{1 17 20 21 23 a}

  
  


• 
  

  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 a e}

  
  


• 
  

  Importance of swallowing tablets whole, without chewing or sucking.^{20 a e}

  
  


• 
  

  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 a e}

  
  


• 
  

  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 a e}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 a}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{1 a}

  
  


• 
  

  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.^d

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 10/2011. 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/$240.00 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

Alendronate Sodium 70MG Tablets (TEVA PHARMACEUTICALS USA): 20/$29.99 or 60/$69.97

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

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

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

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

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. 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.

References

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