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Alendronate

Pronunciation

Pronunciation

(a LEN droe nate)

Index Terms

  • Alendronate Sodium
  • Alendronic Acid Monosodium Salt Trihydrate
  • MK-217

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral:

Generic: 70 mg/75 mL (75 mL)

Tablet, Oral:

Fosamax: 70 mg

Generic: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg

Tablet Effervescent, Oral:

Binosto: 70 mg

Brand Names: U.S.

  • Binosto
  • Fosamax

Pharmacologic Category

  • Bisphosphonate Derivative

Pharmacology

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)

Metabolism

None

Excretion

Urine; feces (as unabsorbed drug)

Half-Life Elimination

Exceeds 10 years

Protein Binding

~78%

Special Populations: Renal Function Impairment

Elimination may be reduced.

Use: Labeled Indications

Osteoporosis: Treatment of osteoporosis in postmenopausal females (Fosamax, Binosto); prevention of osteoporosis in postmenopausal females (Fosamax); treatment of osteoporosis in males (Fosamax, Binosto); treatment of Paget 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 (Fosamax); 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) (Fosamax)

Canadian labeling: Additional use (not in US labeling): Prevention of glucocorticoid-induced osteoporosis in males and females

Contraindications

Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation; hypocalcemia; abnormalities of the esophagus (eg, stricture, achalasia) which delay esophageal emptying; inability to stand or sit upright for at least 30 minutes; increased risk of aspiration (effervescent tablets; oral solution)

Canadian labeling: Additional contraindications (not in US labeling): Renal insufficiency with creatinine clearance <35 mL/minute

Dosing: Adult

Note: Consider discontinuing after 3 to 5 years of use for osteoporosis in patients at low-risk for fracture. Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.

Osteoporosis in postmenopausal females: Oral:

Prophylaxis: 5 mg once daily or 35 mg once weekly

Treatment: 10 mg once daily or 70 mg once weekly

Osteoporosis in males: Oral: Treatment: 10 mg once daily or 70 mg once weekly

Osteoporosis secondary to glucocorticoids in males and females: Oral: Treatment (US labeling) or Treatment and prevention (Canadian labeling): 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen

Paget disease of bone in males and females: Oral: 40 mg once daily for 6 months

Re-treatment: Following a 6-month post-treatment evaluation period, treatment with alendronate may be considered in patients who have relapsed based on increases in serum alkaline phosphatase, which should be measured periodically. Re-treatment may also be considered in those who failed to normalize their serum alkaline phosphatase. The Endocrine Society guidelines suggest re-treatment may be required between 2 and 6 years (Singer 2014).

Missed doses (once weekly): If a once-weekly dose is missed, it should be given the next morning after remembered; may then return to the original once-weekly schedule (original scheduled day of the week), however, do not give 2 doses on the same day.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

CrCl ≥35 mL/minute: No dosage adjustment necessary.

CrCl <35 mL/minute: Use not recommended.

Dosing: Hepatic Impairment

No dosage adjustment necessary.

Reconstitution

Tablet, effervescent (Binosto): Dissolve effervescent tablet in 120 mL of room temperature plain water (not mineral water or flavored water); wait ≥5 minutes after effervescence stops, then stir for 10 seconds and administer.

Administration

Administer first thing in the morning and ≥30 minutes before the first food, beverage (except plain water), or other medication(s) of the day. Do not take with mineral water or with other beverages. Patients should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation).

Oral solution: Administer oral solution, followed with at least 2 oz of plain water.

Tablet (Fosamax): Must be taken with 6 to 8 oz of plain water. The tablet should be swallowed whole; do not chew or suck.

Tablet, effervescent (Binosto): Dissolve one tablet in 4 oz of room temperature plain water only; once effervescence stops, wait ≥5 minutes and stir the solution for ~10 seconds and then drink.

Dietary Considerations

Ensure adequate calcium and vitamin D intake; if dietary intake is inadequate, dietary supplementation is recommended. Women and men should consume:

Calcium: 1,000 mg/day (men: 50 to 70 years) or 1,200 mg/day (women ≥51 years and men ≥71 years) (IOM 2011; NOF [Cosman 2014])

Vitamin D: 800 to 1,000 int. units/day (men and women ≥50 years) (NOF [Cosman 2014]). Recommended Dietary Allowance (RDA): 600 int. units daily (men and women ≤70 years) or 800 int. units/day (men and women ≥71 years) (IOM 2011).

Storage

Oral solution: Store at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze.

Tablet (Fosamax): Store at room temperature of 15°C to 30°C (59°F to 86°F). Keep in well-closed container.

Tablet, effervescent (Binosto): Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture. Store in original blister package until use.

Drug Interactions

Aminoglycosides: May enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy

Antacids: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of antacids containing polyvalent cations within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Magaldrate; Sodium Bicarbonate. Consider therapy modification

Aspirin: May enhance the adverse/toxic effect of Alendronate. Specifically, the incidence of upper gastrointestinal adverse events may be increased Monitor therapy

Calcium Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral calcium supplements within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification

Deferasirox: Bisphosphonate Derivatives may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Iron Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral iron supplements within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Magnesium Salts: May decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral magnesium salts within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Bisphosphonate Derivatives. Specifically, polyvalent cation-containing multivitamins may decrease the absorption of orally-administered bisphosphonate derivatives. Management: Avoid administration of polyvalent cation-containing multivitamins within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Bisphosphonate Derivatives. Specifically, polyvalent cation-containing multivitamins may decrease the absorption of orally-administered bisphosphonate derivatives. Management: Avoid administration of polyvalent cation-containing multivitamins within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Monitor therapy

Parathyroid Hormone: Alendronate may diminish the therapeutic effect of Parathyroid Hormone. More specifically, Alendronate may interfere with normalization of blood calcium concentrations. Avoid combination

Proton Pump Inhibitors: May diminish the therapeutic effect of Bisphosphonate Derivatives. Monitor therapy

Systemic Angiogenesis Inhibitors: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Monitor therapy

Test Interactions

Bisphosphonates may interfere with diagnostic imaging agents such as technetium-99m-diphosphonate in bone scans.

Adverse Reactions

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

>10%: Endocrine & metabolic: Decreased serum calcium (18%; transient, mild)

1% to 10%:

Central nervous system: Headache (3%)

Endocrine & metabolic: Decreased serum phosphate (10%; transient, mild)

Gastrointestinal: Abdominal pain (2% to 7%), acid regurgitation (1% to 5%), flatulence (≤4%), gastroesophageal reflux disease (3%), constipation (≤3%), diarrhea (≤3%), dyspepsia (1% to 3%), nausea (1% to 3%), esophageal ulcer (2%), dysphagia (1%), melena (1%), abdominal distension (≤1%), gastric ulcer (≤1%; may be severe with complications), gastritis (≤1%)

Neuromuscular & skeletal: Musculoskeletal pain (≤6%; includes bone pain, joint pain, and muscle pain), muscle cramps (≤1%)

<1% (Limited to important or life-threatening): Alopecia, cholesteatoma, conjunctivitis, duodenal ulcer (may be severe with complications), dysgeusia, episcleritis, erythema, erosive esophagitis, esophageal perforation, esophageal stenosis, esophageal ulcer, esophagitis, exacerbation of asthma, femur fracture (low energy fractures, including subtrochanteric and diaphyseal), hypersensitivity reaction (includes angioedema and urticaria), hypocalcemia (symptomatic), joint swelling, malaise, oropharyngeal ulcer, osteonecrosis of the jaw (generally associated with tooth extraction and/or local infection with delayed healing), peripheral edema, scleritis, skin rash (occasionally with photosensitivity), Stevens-Johnson syndrome, toxic epidermal necrolysis, uveitis, vertigo, weakness

Warnings/Precautions

Concerns related to adverse effects:

• Bone fractures: Atypical femur fractures have been reported in patients receiving bisphosphonates for treatment/prevention of osteoporosis. The fractures include subtrochanteric femur (bone just below the hip joint) and diaphyseal femur (long segment of the thigh bone). Some patients experience prodromal pain weeks or months before the fracture occurs. It is unclear if bisphosphonate therapy is the cause for these fractures, although the majority of cases have been reported in patients taking bisphosphonates. Patients receiving long-term (>3 to 5 years) therapy may be at an increased risk. Discontinue bisphosphonate therapy in patients who develop a femoral shaft fracture.

• Bone/joint/muscle pain: Severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Consider discontinuing therapy in patients who experience severe symptoms; symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy.

• Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, dysphagia, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; 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). Discontinue use if new or worsening symptoms develop.

• Hypocalcemia: Hypocalcemia has been reported with the use of bisphosphonates. Prior to therapy initiation, hypocalcemia must be corrected; ensure adequate calcium and vitamin D intake.

• Ocular effects: Conjunctivitis, uveitis, episcleritis, and scleritis have been reported with alendronate; patients presenting with signs of ocular inflammation may require further ophthalmologic evaluation.

• Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ), has been reported in patients receiving bisphosphonates. Known risk factors for MRONJ include invasive dental procedures (eg, tooth extraction, dental implants, boney surgery), cancer diagnosis, concomitant therapy (eg, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, ill-fitting dentures, and comorbid disorders (anemia, coagulopathy, infection, preexisting dental or periodontal disease). Risk may increase with increased duration of bisphosphonate use. According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with bisphosphonate and other antiresorptive agents (denosumab), and antiangiogenic agents (eg, bevacizumab, sunitinib) used for the treatment of osteoporosis or malignancy; risk of MRONJ is significantly higher in cancer patients receiving antiresorptive therapy compared to patients receiving osteoporosis treatment (regardless of medication used or dosing schedule). MRONJ risk is also increased with intravenous antiresorptive use compared to the minimal risk associated with oral bisphosphonate use, although risk appears to increase with oral bisphosphonates when duration of therapy exceeds 4 years (AAOMS [Ruggiero 2014]). The manufacturer’s labeling states that in patients requiring invasive dental procedures, discontinuing bisphosphonates may reduce the risk of ONJ and clinical judgment should guide the decision. However, the AAOMS suggests there is currently no evidence that interrupting oral bisphosphonate therapy alters the risk of ONJ following tooth extraction, and that in patients receiving oral bisphosphonates for <4 years who have no clinical risk factors, no alternations or delay in any procedure common to oral/maxillofacial surgeons, periodontists, and other dental providers is necessary (special considerations apply to patients receiving dental implants). Conversely, in patients receiving oral bisphosphonates for >4 years or in patients receiving oral bisphosphonates for <4 years who have also taken corticosteroids or antiangiogenic medications concomitantly, the AAOMS recommends considering a 2-month, drug-free period prior to invasive dental procedures (recommendation based on a theoretical benefit). Patients developing ONJ during therapy should receive care by an oral surgeon (AAOMS [Ruggiero 2014]). According to the manufacturer, discontinuation of the bisphosphonate therapy should be considered (based on risk/benefit evaluation) in patients who develop ONJ.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with CrCl <35 mL/minute).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Effervescent tablet: Each effervescent tablet contains 650 mg of sodium (NaCl 1650 mg). Use with caution in patients following a sodium-restricted diet.

Other warnings/precautions:

• Duration of therapy: In the management of osteoporosis, re-evaluate the need for continued therapy periodically; the optimal duration of treatment has not yet been determined. Consider discontinuing after 3 to 5 years of use in patients at low-risk for fracture; following discontinuation, re-evaluate fracture risk periodically.

Monitoring Parameters

Osteoporosis: Bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 2 years thereafter (NOF [Cosman 2014]); in patients with combined alendronate and glucocorticoid treatment, BMD should be made at initiation and repeated after 6 to 12 months; annual measurements of height and weight, assessment of chronic back pain; serum calcium and 25(OH)D; may consider monitoring biochemical markers of bone turnover

Paget disease: Alkaline phosphatase at 6 to 12 weeks for initial response to treatment (when bone turnover will have shown a substantial decline) and potentially at 6 months (maximal suppression of high bone turnover); following treatment completion, monitor at ~6- to 12-month intervals (Singer 2014); monitoring more specific biochemical markers of bone turnover (eg, serum P1NP, NTX, serum beta-CTx) is generally only warranted in patients with Paget disease who have abnormal liver or biliary tract function or when early assessment of response to treatment is needed (eg, spinal compression, very active disease) (Singer 2014); pain; serum calcium and 25(OH)D

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. It is not known if bisphosphonates cross the placenta, but fetal exposure is expected (Djokanovic 2008; Stathopoulos 2011). Bisphosphonates are incorporated into the bone matrix and gradually released over time. The amount available in the systemic circulation varies by dose and duration of therapy. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy; however, available data have not shown that exposure to bisphosphonates during pregnancy significantly increases the risk of adverse fetal events (Djokanovic 2008; Levy 2009; Stathopoulos 2011). Until additional data is available, most sources recommend discontinuing bisphosphonate therapy in women of reproductive potential as early as possible prior to a planned pregnancy; use in premenopausal women should be reserved for special circumstances when rapid bone loss is occurring (Bhalla 2010; Pereira 2012; Stathopoulos 2011). Because hypocalcemia has been described following in utero bisphosphonate exposure, exposed infants should be monitored for hypocalcemia after birth (Djokanovic 2008; Stathopoulos 2011).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, constipation, or diarrhea. Have patient report immediately to prescriber signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures); black, tarry, or bloody stools; angina; coughing up blood; severe abdominal pain; heartburn; difficulty swallowing; pain when swallowing; pharyngitis; severe nausea; severe vomiting; vomiting blood; severe bone pain; severe joint pain; severe muscle pain; groin, hip, or thigh pain; mouth sores; or jaw pain, or edema (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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