Alendronate (Lexi-Drugs)

Pronunciation

(a LEN droe nate)

Brand Names: US

Binosto; Fosamax

Brand Names: Canada

ACCEL-Alendronate [DSC]; ACH-Alendronate; ACT Alendronate; Alendronate-70; APO-Alendronate; Auro-Alendronate; DOM-Alendronate; DOM-Alendronate-FC; Fosamax; GEN-Alendronate; JAMP-Alendronate; MINT-Alendronate; MYLAN-Alendronate [DSC]; PHL-Alendronate [DSC]; PMS-Alendronate; PMS-Alendronate-FC; Q-Alendronate [DSC]; RAN-Alendronate; RIVA-Alendronate; SANDOZ Alendronate; TEVA-Alendronate; VAN-Alendronate

Pharmacologic Category

Bisphosphonate Derivative

Dosing: Adult

Note: The optimal duration of osteoporosis treatment has not been determined. In postmenopausal women with low fracture risk, consider a drug holiday after 5 years of oral bisphosphonate therapy. In postmenopausal women who remain at high fracture risk, consider extending treatment for up to 10 years (AACE/ACE [Camacho 2016]; Adler 2016). Although evidence is limited, applying these recommendations to treatment duration in older men may be considered (Adler 2016). 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 (to increase bone mass): Oral: Treatment: 10 mg once daily or 70 mg once weekly

Osteoporosis secondary to glucocorticoids in males and females: Oral:

Treatment: 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen.

Prevention (off-label use): 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen (Saag 1998). Note: Use is not recommended in women who are pregnant or who plan on becoming pregnant (ACR [Buckley 2017]).

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.

Bone loss associated with androgen deprivation therapy in prostate cancer, prevention (off-label use): Oral: 70 mg once weekly (Greenspan 2007; Greenspan 2008; Klotz 2013)

Osteogenesis imperfecta (off-label use): Oral: 10 mg once daily (Chevrel 2006) or 70 mg once weekly (Shapiro 2010; Xu 2016).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

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

CrCl <35 mL/minute: Use not recommended.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

Note: Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.

Osteogenesis imperfecta: Limited data available, dosing regimens and efficacy results variable (Akcay 2008; Pizones 2005; Seikaly 2005; Ward 2011): Children ≥2 years and Adolescents:

≤30 kg: Oral: 5 mg once daily

30 to <40 kg: 5 or 10 mg once daily

≥40 kg: Oral: 10 mg once daily

Dosing based on several prospective and retrospective trials; most smaller studies reported increased bone mineral density (BMD), decreased frequency of fractures, alleviation of chronic pain, and in some patients increased mobility (Akcay 2008; Pizones 2005; Seikaly2005; Unal 2005; Vyskocil 2005). The largest trial, a multicenter, randomized, placebo-controlled trial (n=109 in treatment group, n=83 completed 2-year follow-up) reported significant increases in lumbar spine BMD; however, other efficacy markers including long-bone fracture rate and pediatric disability score were no different than placebo (Ward 2011).

Osteopenia associated with cystic fibrosis (CF): Limited data available: Children ≥5 years and Adolescents: Oral:

≤25 kg: 5 mg once daily

>25 kg: 10 mg once daily

Dosing based on a randomized, placebo-controlled trial of CF patients (n=128, treatment group: n=65) with low apparent BMD age and inadequate response to calcium and calcifediol treatment; results showed a significant increase in BMD (16.3% vs 3.1% from baseline); evaluation of effect on fracture rate not possible due to sample size and duration (trial duration: 2 years); alendronate appeared to be well-tolerated with no notable difference in adverse effects reported (Bianchi 2013)

Osteopenia, nonambulatory patients (eg, cerebral palsy, muscular dystrophy): Limited data available, efficacy results variable: Note: Due to added complexity of administration requirements (eg, remaining in an upright position for an extended time) weekly dosing is preferred in these patients.

Fixed dosing (Apkon 2008; Houston 2014; Sholas 2005): Children ≥6 years and Adolescents: Oral: Usual reported dose: 35 mg once weekly. Dosing based on experience in 42 patients (age range: 6 to 16 years) from two case series and a retrospective trial. In the retrospective cohort study (n=29 mean age: 12 years), treatment showed a non-statistically significant trend in Z-score stabilization (Houston 2014). A case series of 10 patients (age range: 6 to 16 years) reported fewer fractures after treatment started compared to the prior year; alendronate was reported as being well tolerated; one patient discontinued therapy for hematemesis (also receiving high-dose ibuprofen therapy) (Sholas 2005).

Weight-directed dosing: Children ≥3 years and Adolescents: Oral: 1 mg/kg/dose once weekly (Paksu 2012)if using a solid dosage form, consider dose rounding to the nearest 10 mg (up or down as appropriate) (Lethaby 2007). Dosing based on a prospective trial of 26 patients (age range: 3 to 17 years); results showed after one year of treatment, increased BMD and decreased alkaline phosphatase.

Osteopenia/Osteoporosis, rheumatology patients (eg, JIA, SLE, dermatomyositis): Limited data available: Children ≥4 years and Adolescents:

≤20 kg: Oral: 5 mg once daily

>20 kg to 30 kg: Oral: 5 or 10 mg once daily

>30 kg: Oral: 10 mg once daily

Dosing based on a prospective trial (multicenter and single center) (Bianchi 2000; Cimaz 2002; Unal 2006); results from trials showed bone mineral density (BMD) was significantly increased (to normal values in some patients) after alendronate therapy; in some cases, bone turnover markers were reduced without a reduction of inflammatory activity (underlying rheumatologic disease process)

Use: Labeled Indications

Osteoporosis:

Binosto: Treatment of osteoporosis in postmenopausal females and to increase bone mass in males with osteoporosis

Fosamax: Treatment and prevention of osteoporosis in postmenopausal females; treatment to increase bone mass in males with osteoporosis; 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)

Paget disease: Fosamax: Treatment of Paget disease of the bone in patients (males and females) who are symptomatic, at risk for future complications, or with alkaline phosphatase ≥2 times the upper limit of normal

Use: Off-Label: Adult

  Bone loss associated with androgen deprivation therapy in prostate cancer (prevention)Level of Evidence [A]

Data from a randomized, double-blind, placebo-controlled crossover study supports the use of once weekly alendronate (in conjunction with calcium and vitamin D supplementation) for the prevention of bone loss associated with androgen deprivation therapy in prostate cancer Ref. Data from a multicenter randomized, double-blind, placebo-controlled study also supports the use of weekly alendronate (in conjunction with calcium and vitamin D supplementation) for prevention of androgen deprivation therapy-associated bone loss Ref.

  Glucocorticoid-induced osteoporosis (prevention)Level of Evidence [A, G]

Based on the 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis, bisphosphonates (including alendronate) are effective and recommended for prevention of glucocorticoid-induced osteoporosis in women (not of childbearing potential, or who do not plan to become pregnant) and men with moderate to high fracture risk and who are initiating long-term glucocorticoid treatment (ACR [Buckley 2017]).

Data from a randomized, placebo-controlled clinical study supports the use of alendronate in the prevention of glucocorticoid-induced osteoporosis Ref.

  Osteogenesis imperfectaLevel of Evidence [B]

Limited initial data from small controlled and noncontrolled trials suggest that oral alendronate may be a cost-effective alternative to IV therapy in the treatment of osteogenesis imperfecta in adults. Larger, controlled trials are needed to verify initial results regarding alendronate’s effects on BMD and to detect its effects on fracture rates in the treatment of osteogenesis imperfecta. Access Full Off-Label Monograph

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Oncology:

National Comprehensive Cancer Network® (NCCN), Clinical Practice Guidelines in Oncology, Prostate Cancer

Osteoporosis:

American Association of Clinical Endocrinologists and American College of Endocrinology, “Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis,” 2016

American College of Physicians, “Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians,” 2017

American College of Rheumatology, “Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis,” 2017

Endocrine Society, “Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline,” 2012

National Osteoporosis Foundation, Clinician’s Guide to Prevention and Treatment of Osteoporosis, 2014

Paget Disease:

The Endocrine Society, “Paget’s Disease of Bone,” 2014

Administration: Oral

Administer first thing in the morning and at least 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.

Administration: Pediatric

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

Oral solution: Follow administration of oral solution 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 on the tablet.

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) or800 int. units/day (men and women ≥71 years) (IOM 2011).

Storage/Stability

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.

Preparation for Administration: Adult

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.

Preparation for Administration: Pediatric

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

Medication Patient Education with HCAHPS Considerations

• 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 health care 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.

Medication Safety Issues
  Sound-alike/look-alike issues:
  International issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Binosto: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM318435.pdf

Fosamax: http://www.merck.com/product/usa/pi_circulars/f/fosamax/fosamax_mg.pdf

Contraindications

Hypersensitivity to alendronate 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 the US labeling): Renal insufficiency with creatinine clearance <35 mL/minute

Documentation of allergenic cross-reactivity for bisphosphonates is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions

Concerns related to adverse effects:

• Bone fractures: Atypical femur fractures (AFF) have been reported in patients receiving bisphosphonates. 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; atypical femur fractures have also been reported in patients not taking bisphosphonates, and in patients receiving glucocorticoids. Patients receiving long-term (>3 to 5 years) bisphosphonate therapy may be at an increased risk (Adler 2016; NOF [Cosman 2014]); however, benefits of therapy (when used for osteoporosis) generally outweigh absolute risk of AFF within the first 5 years of treatment (Adler 2016). Patients presenting with thigh or groin pain with a history of receiving bisphosphonates should be evaluated for femur fracture. Consider interrupting bisphosphonate therapy in patients who develop a femoral shaft fracture; assess for fracture in the contralateral limb.

• 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.

Geriatric Considerations

The elderly are frequently treated long-term for osteoporosis. Elderly patients should be advised to report any lower extremity, jaw (osteonecrosis), or muscle pain that cannot be explained or lasts longer than 2 weeks. Additionally, elderly often receive concomitant diuretic therapy and therefore their electrolyte status (eg, calcium, phosphate) should be periodically evaluated.

Due to the reports of atypical femur fractures and osteonecrosis of the jaw, recommendations for duration of bisphosphonate use in osteoporosis have been modified. Based on available data, consider discontinuing bisphosphonates after 5 years of use in low-risk patients, since the risk of nonvertebral fracture is the same as those patients taking bisphosphonates for 10 years. Those patients with high risk (fracture history) may be continued for a longer period, taking into consideration the risks versus benefits associated with continued therapy.

Warnings: Additional Pediatric Considerations

The potential adverse effects of bisphosphonate therapy on the immature bones of growing children are concerning and data to fully describe are insufficient. Animal data has shown alendronate (high-dose) inhibits longitudinal bone growth (Rauch 2004); pediatric patients with osteogenesis imperfecta (OI) treated with pamidronate for 4 years showed increased height z scores (Zeitlin 2003); pediatric growth effects with other bisphosphonates is lacking. Possible decreased bone remodeling affecting growth or fracture healing may occur with bisphosphonate therapy; a case-report in an adolescent treated with high-dose pamidronate described abnormal long-bone modeling (Rauch 2004); a large, placebo-controlled OI trial (n=109, age range: 4 to 19 years) reported that alendronate did not interfere with fracture healing (Ward 2011). Rapid and in some cases significant weight gain has been reported with pamidronate therapy in pediatric patients which may negatively affect rehabilitation in patients with OI (Zeitlin 2003). Monitor patients closely.

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).

Breast-Feeding Considerations

It is not known if alendronate is excreted into breast milk. The manufacturer recommends that caution be exercised when administering alendronate to nursing women.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Note: Incidence of adverse effects (mostly GI) increases significantly in patients treated for Paget 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%, postmarketing, and/or case reports: Alopecia, conjunctivitis, dizziness, 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), fever, hypersensitivity reaction (includes angioedema and urticaria), hypocalcemia (symptomatic), joint swelling, malaise, oropharyngeal ulcer; osteonecrosis of the jaw, peripheral edema, pruritus, scleritis, skin rash (occasionally with photosensitivity), Stevens-Johnson syndrome, toxic epidermal necrolysis, uveitis, vertigo, weakness

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

None known.

Drug Interactions 

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

Angiogenesis Inhibitors (Systemic): May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: 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. Risk D: Consider therapy modification

Aspirin: May enhance the adverse/toxic effect of Alendronate. Specifically, the incidence of upper gastrointestinal adverse events may be increased Risk C: 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. Risk D: 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. Risk C: 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 Isomaltoside; Iron Sucrose. Risk D: 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. Risk D: 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. Risk D: 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. Risk D: 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. Risk C: Monitor therapy

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

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

Food Interactions

All food and beverages interfere with absorption. Coadministration with dairy products may decrease alendronate absorption. Beverages (especially orange juice, coffee, and mineral water) and food may reduce the absorption of alendronate as much as 60%. Management: Alendronate must be taken first thing in the morning and ≥30 minutes before the first food, beverage (except plain water), or other medication of the day.

Test Interactions

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

Monitoring Parameters

Osteoporosis: Bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 1 to 2 years (or less frequently if stable) thereafter (AACE/ACE [Camacho 2016]; NOF [Cosman 2014]); in patients with combined alendronate and glucocorticoid treatment, evaluate BMD at initiation of glucocorticoid therapy and after 6 to 12 months, then every 2 to 3 years if patient continues to have significant osteoporosis risk factors (ACR [Buckley 2017]); 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

Reference Range

Calcium (total): Adults: 9.0 to 11.0 mg/dL (2.05 to 2.54 mmol/L), may slightly decrease with aging

Phosphorus: 2.5 to 4.5 mg/dL (0.81 to 1.45 mmol/L)

Vitamin D: There is no clear consensus on a reference range for total serum 25(OH)D concentrations or the validity of this level as it relates clinically to bone health. In addition, there is significant variability in the reporting of serum 25(OH)D levels as a result of different assay types in use; however, the following ranges have been suggested:

Adults (IOM 2011): Sufficient levels in practically all persons: ≥20 ng/mL (50 nmol/L); concern for risk of toxicity: >50 ng/mL (125 nmol/L)

Osteoporosis patients (NOF [Cosman 2014]): Recommended level to reach and maintain: ~30 ng/mL (75 nmol/L)

Advanced Practitioners Physical Assessment/Monitoring

Obtain serum calcium and 25(OH)D. Evaluate bone mineral density every 1 to 2 years after initiation. In patients also receiving glucocorticoid therapy evaluate BMD at initiation of glucocorticoid, 6 to 12 months after, and then every 2 to 3 years. Assess height and weight annually. Assess for chronic back pain. Consider obtaining biochemical markers of bone turnover. Obtain alkaline phosphatase every 6 to 12 weeks in patients with Paget disease. Education patient on proper administration technique as well as proper diet.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Teach patient proper administration technique. Instruct patient in lifestyle and dietary changes that may optimize bone strength. Monitor for and educate patient to report any back pain. Educate patient about need for good oral hygiene and regular dental exams.

Dosage Forms: US

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

Dosage Forms: Canada

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

Tablet, Oral:

Fosamax: 70 mg

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

Anatomic Therapeutic Chemical (ATC) Classification
  • M05BA04
Generic Available (US)

May be product dependent

Pricing: US

Solution (Alendronate Sodium Oral)

70 mg/75 mL (per mL): $0.76

Tablet, effervescent (Binosto Oral)

70 mg (per each): $60.48

Tablets (Alendronate Sodium Oral)

5 mg (per each): $2.92 – $2.93

10 mg (per each): $2.93

35 mg (per each): $20.48 – $20.63

40 mg (per each): $6.60

70 mg (per each): $20.41 – $20.49

Tablets (Fosamax Oral)

70 mg (per each): $38.35

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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 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.

Pharmacodynamics/Kinetics

Distribution: 28 L (exclusive of bone)

Protein binding: ~78%

Metabolism: None

Bioavailability: Fasting:

Children ≥4 years and Adolescents: Mean range: 0.41% to 0.56% (Nakhla 2011; Ward 2005)

Adults: 0.6%; reduced up to 60% with coffee or orange juice

Half-life elimination: Exceeds 10 years

Excretion: Urine; feces (as unabsorbed drug)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Elimination may be reduced.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

A review of 2,408 published cases of bisphosphonate-associated osteonecrosis of the jaw bone (BP-associated ONJ) was done by Filleul 2010. BP therapy was associated with 89% of the cases to treat malignancies and 11% of the cases to treat nonmalignant conditions. Information on the specific bisphosphonate used was available for 1,694 of the patients. Intravenous therapy (primarily zoledronic acid) was received by 88% of the patients and 12% received oral treatment (primarily alendronate). Of all the cases of BP-associated ONJ, 67% were preceded by tooth extraction and for 26% of patients, there was no predisposing factor identified.

A 2010 retrospective case review reported the prevalence of BP-associated ONJ in patients using alendronate-type drugs was one out of 952 patients or ~0.1% (Lo 2010). Of the 8,572 respondents, nine cases of ONJ were identified; five had developed ONJ spontaneously and four developed ONJ after tooth extraction. When extrapolated to patient-years of bisphosphonate exposure, this prevalence rate of 0.1% equates to a frequency of 28 cases per 100,000 person-years of oral bisphosphonate treatment. An Australian group (Mavrokokki 2007), identified the frequency of BP-associated ONJ in osteoporotic patients, mainly taking weekly oral alendronate, was 1 in 8,470 to 1 in 2,260 (0.01% to 0.04%) patients. If extractions were carried out, the calculated frequency was 1 in 1,130 to 1 in 296 (0.09% to 0.34%) patients. The median time to onset of ONJ in alendronate patients was 24 months.

According to the 2011 report by the American Dental Association (ADA), the incidence of BP-associated ONJ remains low and the benefits of using oral bisphosphonates significantly outweighs the risk of developing BP-associated ONJ for treatment and prevention of osteoporosis and cancer treatment (Hellstein 2011). The full 47-page report can be accessed at http://www.ada.org/~/media/ADA/Member%20Center/FIles/topics_ARONJ_report.ashx.

The ADA review of 2011 stated the incidence of oral BP-associated ONJ was one case for every 1,000 individuals exposed to oral bisphosphonates (0.1%) (Hellstein 2011).

The most comprehensive review to date on osteonecrosis of the jaw bone (ONJ) has been published in the Journal of Bone and Mineral Research (Khan 2015), and written by an International Task Force of authors, totaling 34, from academe; industry; clinical medical and dental practice; oral and maxillofacial surgery; bone and mineral research; epidemiology; medical and dental oncology; orthopedic surgery; osteoporosis research; muscle and bone research; endocrinology and diagnostic sciences. The work provides a systematic review of the literature and international consensus on the classification, incidence, pathophysiology, diagnosis, and management of ONJ in both oncology and osteoporosis patient populations. This review of the literature from January 2003 to April 2014, with 299 references, offers recommendations for management of ONJ based on multidisciplinary international consensus.

Prevalence and incidence of ONJ in osteoporosis patients from the Task Force report:

Prevalence – the percent of osteoporotic population affected with ONJ

After reviewing all literature reports on this subject, the Task Force concluded that the prevalence of ONJ in patients prescribed oral BPs for the treatment of osteoporosis ranges from 0% to 0.04% with the majority being below 0.001%. However, the Task Force does cite the study of (Lo et al) that evaluated the Kaiser Permanente database and found the prevalence of ONJ in those receiving BPs for more than 2 years to range from 0.05% to 0.21% and appeared to be related to duration of exposure. As mentioned above, the American Dental Association has previously reported that the prevalence of ONJ in osteoporosis patients using oral BPs to be 1 out of 1,000 or 0.1% (Hellstein 2011).

Incidence – the rate at which ONJ occurs or the number of times it happens

From currently available data, the incidence of ONJ in the osteoporosis patient population appears to be low ranging from 0.15% to less than 0.001% person-years drug exposure. In terms of the osteoporosis patient population taking oral BPs, the incidence ranges from 1.04 to 69 per 100,000 patient years of drug exposure.

Effects on Dental Treatment

Osteonecrosis of the jaw (ONJ), generally associated with local infection and/or tooth extraction and often with delayed healing, has been reported in patients taking bisphosphonates. Symptoms included nonhealing extraction socket or an exposed jawbone. Most reported cases of bisphosphonate-associated osteonecrosis have been in cancer patients treated with intravenous bisphosphonates. However, some have occurred in patients with postmenopausal osteoporosis taking oral bisphosphonates. The risk of developing ONJ in patients taking oral bisphosphonates remains low with an estimated prevalence of 0.1% (one out of every 1000 cases of patients exposed to oral bisphosphonates). The benefits of using the oral bisphosphonates to prevent osteoporosis significantly outweighs the small risk of developing bisphosphonate-associated ONJ. Also, at the present time, there are no validated diagnostic techniques to determine which patients are at increased risk of developing ONJ. ONJ in patients taking these drugs can occur spontaneously. In addition, the risk of ONJ increases with specific procedures that increase bone trauma, particularly tooth extractions. Other factors that increase risk of ONJ in patients taking these drugs are age (>65 years of age), periodontitis, use of bisphosphonates for >2 years, smoking, wearing dentures, and diabetes. Patients who develop ONJ while on bisphosphonate therapy should receive care by an oral surgeon. See Dental Health Professional Considerations.

Effects on Bleeding

No information available to require special precautions

Index Terms

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

FDA Approval Date
September 29, 1995
References

Adler RA, El-Hajj Fuleihan G, Bauer DC, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a Task Force of the American Society for Bone and Mineral Research [published correction appears in J Bone Miner Res. 2016;31(10):1910]. J Bone Miner Res. 2016;31(1):16-35. doi: 10.1002/jbmr.2708.[PubMed 26350171]

Akcay T, Turan S, Guran T, Bereket A. Alendronate treatment in children with osteogenesis imperfecta. Indian Pediatr. 2008;45(2):105-109[PubMed 18310788]

Alendronate sodium tablet [prescribing information]. Dayton, NJ: Aurobindo Pharma; August 2016.

American Dental Association Council on Scientific Affairs, “Dental Management of Patients Receiving Oral Bisphosphonate Therapy,” JADA, 2006, 137(8):1144-50. Available at http://jada.ada.org/article/S0002-8177(14)64960-6/pdf[PubMed 16873332]

Author Unknown, “Safety Update: Bone-Building Drugs: Risks Explained,” Consum Rep Health, 2006, 18(5):3.

Bhalla AK, “Management of Osteoporosis in a Pre-menopausal Woman,” Best Pract Res Clin Rheumatol, 2010, 24(3):313-27.[PubMed 20534366]

Binosto (alendronate) [prescribing information]. San Antonio, TX: Mission Pharmacal Company; January 2017.

Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol. 2017;69(8):1521-1537.[PubMed 28585373]

Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis–2016: executive summary [published correction appears in Endocr Pract. 2017;23(3):383]. Endocr Pract. 2016;22(9):1111-1118. doi: 10.4158/EP161435.ESGL.[PubMed 27643923]

Cartsos VM, Zhu S, and Zavras AI, “Bisphosphonate Use and the Risk of Adverse Jaw Outcomes: A Medical Claims Study of 714,217 People,” J Am Dent Assoc, 2008, 139(1):23-30.[PubMed 18167381]

Chevrel G, Schott AM, Fontanges E, et al. Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial. J Bone Miner Res. 2006;21(2):300-306[PubMed 16418786]

Chesnut CH 3rd, McClung MR, Ensrud KE, et al. Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling. Am J Med. 1995;99(2):144-152.[PubMed 7625419]

Christodoulou C, Pervena A, Klouvas G, et al. Combination of bisphosphonates and antiangiogenic factors induces osteonecrosis of the jaw more frequently than bisphosphonates alone. Oncology. 2009;76(3):209-211.[PubMed 19212145]

Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2381. doi: 10.1007/s00198-014-2794-2.[PubMed 25182228]

Djokanovic N, Klieger-Grossmann C, and Koren G, “Does Treatment With Bisphosphonates Endanger the Human Pregnancy?” J Obstet Gynaecol Can, 2008, 30(12):1146-8.[PubMed 19175968]

Durie BG, Katz M, and Crowley J, “Osteonecrosis of the Jaw and Bisphosphonates,” N Engl J Med, 2005, 353(1):99-102.[PubMed 16000365]

Edwards BJ, Hellstein JW, Jacobsen PL, et al, “Updated Recommendations for Managing the Care of Patients Receiving Oral Bisphosphonate Therapy: An Advisory Statement From the American Dental Association Council on Scientific Affairs,” J Am Dent Assoc, 2008, 139(12):1674-7.[PubMed 19047674]

Filleul O, Crompot E, and Saussez S, “Bisphosphonate-Induced Osteonecrosis of the Jaw: A Review of 2,400 Patient Cases,” J Cancer Res Clin Oncol, 2010, 136(8):1117-24.[PubMed 20508948]

Fosamax (alendronate) [prescribing information]. Whitehouse Station, NJ: Merck & Co Inc; March 2016.

Fosamax (alendronate) [product monograph]. Kirkland, Quebec, Canada: Merck Canada Inc; May 2017.

French AE, Kaplan N, Lishner M, et al, “Taking Bisphosphonates During Pregnancy,” Can Fam Physician, 2003, 49:1281-2.[PubMed 14594094]

Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med. 2007;146(6):416-424.[PubMed 17371886]

Greenspan SL, Nelson JB, Trump DL, et al. Skeletal health after continuation, withdrawal, or delay of alendronate in men with prostate cancer undergoing androgen-deprivation therapy. J Clin Oncol. 2008;26(27):4426-4434.[PubMed 18802155]

Hellstein JW, Adler RA, Edwards B, et al, “Managing the Care of Patients Receiving Antiresorptive Therapy for Prevention and Treatment of Osteoporosis: Executive Summary of Recommendations From the American Dental Association Council on Scientific Affairs,” J Am Dent Assoc, 2011, 142(11):1243-51.[PubMed 22041409]

Hellstein JW, Adler RA, Edwards B, et al, “Managing the Care of Patients Receiving Antiresorptive Therapy for Prevention and Treatment of Osteoporosis: Recommendations From the American Dental Association Council on Scientific Affairs,” 2011, Available at http://www.ada.org/~/media/ADA/Member%20Center/FIles/topics_ARONJ_report.ashx. Accessed February 2013.

IOM (Institute of Medicine), Dietary Reference Intakes for Calcium and Vitamin D, Washington, DC: The National Academies Press, 2011.

Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015; 30(1):3-23.[PubMed 25414052]

Klotz LH, McNeill IY, Kebabdjian M, Zhang L, Chin JL; Canadian Urology Research Consortium. A phase 3, double-blind, randomised, parallel-group, placebo-controlled study of oral weekly alendronate for the prevention of androgen deprivation bone loss in nonmetastatic prostate cancer: the Cancer and Osteoporosis Research with Alendronate and Leuprolide (CORAL) study. Eur Urol. 2013;63(5):927-935.[PubMed 23040208]

Levy S, Fayez I, Taguchi N, et al, “Pregnancy Outcome Following in utero Exposure to Bisphosphonates,” Bone, 2009, 44(3):428-30.[PubMed 19059370]

Lo JC, O’Ryan FS, Gordon NP, et al, “Prevalence of Osteonecrosis of the Jaw in Patients With Oral Bisphosphonate Exposure,” J Oral Maxillofac Surg, 2010, 68(2):243-53.[PubMed 19772941]

“Management of Osteoporosis in Postmenopausal Women: 2010 Position Statement of The North American Menopause Society,” Menopause, 2010, 17(1):25-54.[PubMed 20061894]

Marx RE, Sawatari Y, Fortin M, et al, “Bisphosphonate-Induced Exposed Bone (Osteonecrosis/Osteopetrosis) of the Jaws: Risk Factors, Recognition, Prevention, and Treatment,” J Oral Maxillofac Surg, 2005, 63(11):1567-75.[PubMed 16243172]

Mavrokokki T, Cheng A, Stein B, et al, “Nature and Frequency of Bisphosphonate-Associated Osteonecrosis of the Jaws in Australia,” J Oral Maxillofac Surg, 2007, 65(3):415-23.[PubMed 17307586]

Nakhla M, Denker AE, Connor JD, et al. Bioavailability and short-term tolerability of alendronate in glucocorticoid-treated children. Clin Ther. 2011;33(10):1516-1523.[PubMed 21962451]

Orwoll E, Ettinger M, Weiss S, et al, “Alendronate for the Treatment of Osteoporosis in Men,” N Engl J Med, 2000, 343(9):604-10.[PubMed 10979796]

Pereira RM, Carvalho JF, Paula AP, et al, “Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis,” Rev Bras Reumatol, 2012, 52(4):580-93.[PubMed 22885424]

Pizones J, Plotkin H, Parra-Garcia JI, et al. Bone healing in children with osteogenesis imperfecta treated with bisphosphonates. J Pediatr Orthop. 2005;25(3):332-335[PubMed 15832149]

Ralston SH, “Pathogenesis of Paget’s Disease of Bone,” Bone, 2008, 43(5):819-25.[PubMed 18672105]

Ruggiero SL, Dodson TB, Fantasia J, et al; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw–2014 update. J Oral Maxillofac Surg. 2014;72(10):1938-1956. doi: 10.1016/j.joms.2014.04.031.[PubMed 25234529]

Ruggiero S, Gralow J, Marx RE, et al, “Practical Guidelines for the Prevention, Diagnosis, and Treatment of Osteonecrosis of the Jaw in Patients With Cancer,” J Clin Oncol, 2006, 2(1):7-14.

Saag KG, Emkey R, Schnitzer TJ, et al, Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis, Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med. 1998;339(5):292-299.[PubMed 9682041]

Sellmeyer DE, “Atypical Fractures as a Potential Complication of Long-term Bisphosphonate Therapy,” JAMA, 2010, 304(13):1480-4.[PubMed 20924014]

Shapiro JR, Thompson CB, Wu Y, Nunes M, Gillen C. Bone mineral density and fracture rate in response to intravenous and oral bisphosphonates in adult osteogenesis imperfecta. Calcif Tissue Int. 2010;87(2):120-129[PubMed 20544187]

Shane E, Burr D, Ebeling PR, et al, “Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Report of a Task Force of the American Society for Bone and Mineral Research,” J Bone Miner Res, 2010, 25(11):2267-94.[PubMed 20842676]

Singer FR, Bone HG, Hosking DJ, et al. Paget’s disease of bone: an Endocrine Society practice guideline. J Clin Endocrinol Metab. 2014;99(12):4408-4422.[PubMed 25406796]

Stathopoulos IP, Liakou CG, Katsalira A, et al, “The Use of Bisphosphonates in Women Prior to or During Pregnancy and Lactation,” Hormones (Athens)’, 2011, 10(4):280-91.[PubMed 22281884]

Ward LM, Rauch F, Whyte MP, et al. Alendronate for the treatment of pediatric osteogenesis imperfect: a randomized placebo-controlled study. J Clin Endocrinol Metab. 2011;96(2):355-364.[PubMed 21106710]

Watts NB, “Treatment of Osteoporosis With Bisphosphonates,” Rheum Dis Clin North Am, 1994, 20(3):717-34.[PubMed 7984786]

Whyte MP, “Clinical Practice. Paget’s Disease of Bone,” N Engl J Med, 2006, 355(6):593-600.[PubMed 16899779]

Wysowski DK, “Reports of Esophageal Cancer With Oral Bisphosphonate Use,” N Engl J Med, 2009, 360(1):89-90.[PubMed 19118315]

Xu XJ, Ma DD, Lv F, et al. The clinical characteristics and efficacy of bisphosphonates in adult patients with osteogenesis imperfecta. Endocr Pract. 2016;22(11):1267-1276.[PubMed 27482615]

Brand Names: International

Adronat (AU, IT, PT); Adronik (RO); Aldren 70 (PH, TH); Aldron (HR); Aldrox (CL); Alenato (AR); Alend (KR); Alendomax (JO); Alendra (PH, UA); Alendrate (NZ); Alendrex (NZ); Alendro (AU, LK, SA); Alendro Once Weekly (KW); Alendrobell (AU); Alendronate (TH); Alendros (KR); Alendroxl (PH); Alenfos (KR); Alenfosa (VN); Allentop (HK); Alnate (LK); Alovell (ID, PH, VN); Arendal (PE); Armol (CR, DO, GT, HN, NI, PA, SV); Bifosa (IN); Binosto (MY, SG); Bisbon (KR); Bonafide (LK); Bonaid (KR); Bonalene (EG); Bonalon (JP); Bonapex (EG); Bonmax (JO); BonMax (TH); Calidron (JO); Densate (AU); Drate (LK); Endronax (BR); Fonat (AU); Forosa (PH); Fosalan (IL); Fosamax (AE, AR, AT, AU, BB, BE, BG, BH, BM, BR, BS, BZ, CH, CL, CN, CY, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GR, GY, HR, IE, IT, JM, JO, KR, KW, LB, LK, LU, MT, MX, NL, NO, NZ, PE, PK, PL, PR, PT, QA, RO, RU, SA, SE, SG, SI, SK, SR, TR, TT, TW, VE, VN); Fosamax Once Weekly (AE, BH, HK, LB, SA); Fosmin (EC, PE); Fostepor (IE); Fostolin (IE); Fosval (PY); Gendarin (SE); Gubang (CN); Kalosten (CR, DO, GT, HN, NI, PA, SV); Lendomax (AE); Londromax (UA); Malend (KR); Marvil (LB, PE, UY); MaxiBone (IL); MaxiBone 70 (IL); Maxlen (TH); Nichospor (ID); Oseomax (CR, DO, GT, HN, NI, PA, SV); Oseotenk (AR); Osficar (CO); Ostemax (UA); Osteo-Plus (PH); Osteocor (PH); Osteodron (PH); Osteofar (ID); Osteofos (HK, IN, UA); Osteol (PY); Osteomax (PH); Osteomel (IE); Osteopor (UY); Osteosan (CL); Osteovan (CR); Osteve (QA); Ostex (CO); Osto (LK); Porosal (VE); Prevost (VN); Reventa (PH); Romax (IE); Tevanate (BG, TW); Valora (HR); Zeroclast (CR, DO, GT, HN, NI, PA, SV)

Alendronate (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(a LEN droe nate)

Brand Names: US

Binosto; Fosamax

Brand Names: Canada

Fosamax

What is this drug used for?
  • It is used to prevent or treat soft, brittle bones (osteoporosis).
  • It is used to treat Paget’s disease.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to alendronate or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: A swallowing tube (esophagus) that is not normal, low calcium levels, kidney disease, or trouble swallowing.
  • If you are not able to stand or sit up for 30 minutes.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • For all patients taking this drug:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Very bad swallowing tube (esophagus) problems like irritation, swelling, ulcers, and bleeding have happened with this drug. Talk with the doctor.
  • Worsening of asthma has happened in people taking drugs like this one. Talk with the doctor.
  • This drug may raise the chance of a broken leg. Talk with the doctor.
  • Have a bone density test as you have been told by your doctor. Talk with your doctor.
  • This drug works best when used with calcium/vitamin D and weight-bearing workouts like walking or PT (physical therapy).
  • Follow the diet and workout plan that your doctor told you about.
  • Have a dental exam before starting this drug.
  • Take good care of your teeth. See a dentist often.
  • Talk with your doctor before you drink alcohol.
  • If you smoke, talk with your doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Children:
  • This drug is not approved for use in children. However, the doctor may decide the benefits of taking this drug outweigh the risks. If your child has been given this drug, ask the doctor for information about the benefits and risks. Talk with the doctor if you have questions about giving this drug to your child.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low calcium levels like muscle cramps or spasms, numbness and tingling, or seizures.
  • Black, tarry, or bloody stools.
  • Chest pain.
  • Coughing up blood.
  • Very bad belly pain.
  • Heartburn.
  • Trouble swallowing.
  • Very bad pain when swallowing.
  • Sore throat.
  • Very upset stomach or throwing up.
  • Throwing up blood or throw up that looks like coffee grounds.
  • Very bad bone, joint, or muscle pain.
  • Any new or strange groin, hip, or thigh pain.
  • Mouth sores.
  • This drug may cause jawbone problems. The risk may be higher the longer you take this drug. The risk may be higher if you have cancer, dental problems, dentures that do not fit well, anemia, blood clotting problems, or an infection. The risk may also be higher if you are having dental work, get chemo or radiation, or take other drugs that may cause jawbone problems (like some steroid drugs). Talk with your doctor if any of these apply to you, if you will be having dental work, or if you take other drugs that may cause jawbone problems. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure. Call your doctor right away if you have jaw swelling or pain.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Belly pain.
  • Upset stomach or throwing up.
  • Headache.
  • Constipation.
  • Diarrhea.
  • Muscle or joint pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take on an empty stomach before breakfast.
  • Take at least 30 minutes before the first food, drink, or drugs of the day.
  • Do not lie down for at least 30 minutes after taking this drug and until you eat your first food of the day.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • To gain the most benefit, do not miss doses.
  • Tablets:
  • Take with a full glass of water.
  • Take with plain water only. Avoid taking with mineral water, milk, or other drinks.
  • Swallow whole. Do not chew, break, or crush.
  • Effervescent tablets:
  • Dissolve the effervescent tablet in 1/2 cup of water. Do not swallow the tablet whole.
  •  When the water stops bubbling, wait at least 5 more minutes then stir for about 10 seconds and drink.
  • Take with plain water only. Avoid taking with mineral water, milk, or other drinks.
  • Liquid (solution):
  • Drink 1/4 cup of water after taking your full dose.
  • Take with plain water only. Avoid taking with mineral water, milk, or other drinks.
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if I miss a dose?
  • Do not take it later in the day.
  • Take the missed dose on the next morning after you think about it and then go back to your normal time.
  • Do not take 2 doses on the same day.
How do I store and/or throw out this drug?
  • All products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Effervescent tablets:
  • Store in original container.
  • Liquid (solution):
  • Do not freeze.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Alendronate (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(a LEN droe nate)

Brand Names: US

Binosto; Fosamax

Brand Names: Canada

Fosamax

What is this drug used for?
  • It is used to help with some bone problems.
  • Effervescent tablets:
  • If your child has been given this form of this drug, talk with the doctor for information about the benefits and risks. Talk with the doctor if you have questions or concerns about giving this drug to your child.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has any of these health problems: A swallowing tube (esophagus) that is not normal, low calcium levels, kidney disease, or trouble swallowing.
  • If your child is not able to stand or sit up for 30 minutes.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Very bad swallowing tube (esophagus) problems like irritation, swelling, ulcers, and bleeding have happened with this drug. Talk with the doctor.
  • Worsening of asthma has happened in people taking drugs like this one. Talk with the doctor.
  • This drug may raise the chance of a broken leg. Talk with the doctor.
  • Have your child get a bone density test as you have been told by your child’s doctor.
  • Give calcium and vitamin D as you were told by your child’s doctor.
  • Have your child follow the diet plan your child’s doctor told you about.
  • Have your child get a dental exam before starting this drug.
  • Take care of your child’s teeth. See a dentist often.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • If your child smokes, talk with the doctor.
  • This drug is not approved for use in children. However, the doctor may decide the benefits of taking this drug outweigh the risks. If your child has been given this drug, ask the doctor for information about the benefits and risks. Talk with the doctor if you have questions about giving this drug to your child.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low calcium levels like muscle cramps or spasms, numbness and tingling, or seizures.
  • Black, tarry, or bloody stools.
  • Chest pain.
  • Coughing up blood.
  • Very bad belly pain.
  • Heartburn.
  • Trouble swallowing.
  • Very bad pain when swallowing.
  • Sore throat.
  • Very upset stomach or throwing up.
  • Throwing up blood or throw up that looks like coffee grounds.
  • Very bad bone, joint, or muscle pain.
  • Any new or strange groin, hip, or thigh pain.
  • Mouth sores.
  • This drug may cause jawbone problems. The risk may be higher the longer your child takes this drug. The risk may be higher if your child has cancer, dental problems, dentures that do not fit well, anemia, blood clotting problems, or an infection. The risk may also be higher if your child is having dental work, gets chemo or radiation, or takes other drugs that may cause jawbone problems (like some steroid drugs). Talk with your child’s doctor if any of these apply to your child, if your child will be having dental work, or if your child takes other drugs that may cause jawbone problems. There are many drugs that can do this. Ask your child’s doctor or pharmacist if you are not sure. Call your child’s doctor right away if your child has jaw swelling or pain.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Belly pain.
  • Upset stomach or throwing up.
  • Headache.
  • Constipation.
  • Diarrhea.
  • Muscle or joint pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give on an empty stomach before breakfast.
  • Give at least 30 minutes before the first food, drink, or drugs of the day.
  • Do not let your child lie down for at least 30 minutes after taking this drug and until your child eats the first food of the day.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Tablets:
  • Give this drug with a full glass of water.
  • Give this drug with plain water only. Avoid giving with mineral water or other drinks.
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • Liquid (solution):
  • Have your child drink 1/4 cup of water after taking the full dose.
  • Give this drug with plain water only. Avoid giving with mineral water or other drinks.
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if my child misses a dose?
  • Do not give it later in the day.
  • Give the missed dose on the next morning after you think about it and then go back to your child’s normal time.
  • Do not give 2 doses on the same day.
How do I store and/or throw out this drug?
  • All products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Liquid (solution):
  • Do not freeze.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.