alendronate (Fosamax, Binosto, Fosamax Plus D)

Dosing and uses of Fosamax, Binosto (alendronate)

• Adult
• Pediatric

 

Adult dosage forms and strengths

tablet

• 5mg
• 10mg
• 35mg
• 40mg
• 70mg

tablet for solution (effervescent)

• 70mg

solution, oraL

• 70mg/75mL

 

Osteoporosis

Prevention in postmenopausal women

• 5 mg PO once daily or 35 mg PO once weekly

Treatment in postmenopausal women and men

• 10 mg PO once daily or 70 mg PO once weekly

 

Glucocorticoid-Induced Osteoporosis

Males and females: 5 mg PO once daily (10 mg/day for postmenopausal women not on hormone replacement therapy)

 

Paget Disease

40 mg/day PO for 6 months

 

Dosing Modifications

Mild-to-moderate renal impairment (CrCl 35-60 mL/min): Dose adjustment not necessary

Severe renal impairment (CrCl <35 mL/min): Not recommended

 

Administration

Take only in morning, not at bedtime or before arising

Take tablet with full glass of water (6-8 oz) at least 30 minutes before first food or drink of day, in upright position

Administer oral solution with at least 2 ounces of water

Swallow with plain water only; mineral water, coffee, juice or other beverages severely reduces bioavailability

Swallow tablet whole; do not suck or chew

Do not lie down for 30 minutes after taking drug; sit or stand upright

Despite long terminal half-life (10 years), bone-incorporated drug is not pharmacologically active

If dietary intake is inadequate, patients should receive calcium supplement and vitamin d

 

Limitation of Use

Optimal duration of use not determined; for patients at low-risk for fracture, consider drug discontinuation after 3-5 years of use

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Osteogenesis Imperfecta (Orphan)

Treatment in pediatric patients aged 4 years or older

Orphan indication sponsor

• Merck, Sharpe & Dohme Corp; 126 East Lincoln Ave, PO Box 2000; Rahway, NJ 07065-0900

 

Gaucher Disease (Orphan)

Treatment of bone manifestations of disease

Orphan indication sponsor

• Richard J Wenstrup, MD; Division of Human Genetics, Children's Hospital Research Foundation; Cincinnati, OH 45229-3039

 

Fosamax, Binosto (alendronate) adverse (side) effects

>10%

Hypocalcemia, transient and mild (18%)

 

1-10%

Hypophosphatemia, transient and mild (10%)

Abdominal pain (7%)

Musculoskeletal pain (4.1%)

Dyspepsia (3.6%)

Nausea (3.6%)

Constipation (3.1%)

Diarrhea (3.1%)

Flatulence (2.6%)

Headache (2.6%)

Acid regurgitation (2%)

Esophagitis (1.5%)

Abdominal distention (1%)

 

<1%

Alopecia

Diaphyseal femur fracture

Esophageal cancer

Flulike syndrome

Gastritis

Myalgia

Oropharyngeal ulceration

Pruritus

Rash

Taste perversion

Toxic epidermal necrolysis

Uveitis

Vertigo

Weakness

 

Postmarketing Reports

Body as a whole: Hypersensitivity reactions including urticaria and angioedema; transient myalgia, malaise, asthenia, and fever; symptomatic hypocalcemia; peripheral edema

Gastrointestinal: Esophagitis, esophageal erosions, esophageal ulcers, esophageal stricture or perforation, and oropharyngeal ulceration; gastric or duodenal ulcers

Localized osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection with delayed healing

Musculoskeletal: Bone, joint, and/or muscle pain, occasionally severe, and incapacitating; joint swelling; low-energy femoral shaft and subtrochanteric fractures

Nervous system: dizziness, vertigo

Pulmonary: Acute asthma exacerbations

Skin: Rash (occasionally with photosensitivity), pruritus, alopecia, severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis

Special Senses: Uveitis, scleritis, or episcleritis, cholesteatoma of the external auditory canal (focal osteonecrosis)

 

Warnings

Contraindications

Hypersensitivity

Hypocalcemia

Abnormalities of the esophagus delaying esophageal emptying such as stricture or achalasia

Inability to stand or sit upright for 30 minutes

 

Cautions

May cause local irritation of upper GI mucosa

Take with plain water only, not coffee, juice, or mineral water; sit or stand upright for at least 30 minutes after administration

Hypocalcemia reported with use of bisphosphonates; correct hypocalcemia prior to therapy; ensure adequate calcium and vitamin D intake

Conjunctivitis, uveitis, episcleritis, and scleritis reported with alendronate use; perform ophthalmic evaluation in patients with signs of ocular inflammation

Avoid concomitant polyvalent cation-containing medications

Osteonecrosis of the jaw, can occur spontaneously and is generally associated with tooth extraction and/or local infection with delayed healing; known risk factors include invasive dental procedures (e.g., tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders; risk of osteonecrosis of the jaw may increase with duration of exposure to bisphosphonates

Not recommended in severe renal impairment (CrCl <35 mL/min)

In Paget disease, drug is available only through Paget's Patient Support Program with Pharma Care Specialty Pharmacy (800-238-7828 x58197) distribution system for 40-mg dosage regimen

Risk of severe bone, joint, or muscle pain; discontinue therapy in patients who experience severe symptoms of pain; avoid use in patients with history of these symptoms in association with bisphosphonate therapy

Possible increased risk of atypical subtrochanteric and diaphyseal femur fractures; may consider discontinuing therapy after 3-5 years in patients at low-risk for fracture; following discontinuation, re-evaluate fracture risk periodically; consider periodic reevaluation of need for continued bisphosphonate therapy, particularly if treatment lasts >5 years; patients with new thigh or groin pain should be evaluated to rule out a femoral fracture

Use effervescent tablet with caution in sodium-restricted patients (tablet contains 650 mg of sodium)

Esophageal cancer risk (July 21, 2011, FDA safety communication)

• Conflicting findings exist from studies evaluating risk of esophageal cancer with oral bisphosphonates
• Esophagitis, dysphagia, esophageal ulcers, esophageal erosions, and esophageal stricture reported with oral bisphosphonates; risk is higher in patients unable to closely follow dosing instructions (eg, sitting up or standing after administration and taking with full glass of water); use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers; discontinue use if new or worsening symptoms develop
• An ongoing review of data from published studies to evaluate whether use of oral bisphosphonates is associated with an increased risk of cancer of the esophagus is currently being conducted by FDA
• FDA has not concluded that taking an oral bisphosphonate increases risk of esophageal cancer
• Data are insufficient to recommend endoscopic screening of asymptomatic patients
• FDA will continue to evaluate all available data supporting safety and effectiveness of bisphosphonates and will update public when more information becomes available
• Instruct patients to contact their healthcare provider if they develop symptoms of esophagitis (eg, swallowing difficulties, chest pain, new or worsening heartburn, trouble or pain when swallowing)

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Unknown whether drug is excreted in milk; use with caution

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Fosamax, Binosto (alendronate)

Mechanism of action

Bisphosphonate; binds to hydroxyapatite crystals in bone and inhibits osteoclast-mediated bone resorption; decreases mineral release and collagen or matrix breakdown in bone

 

Absorption

Bioavailability (fasting): Women, 0.64%; men, 0.59%; reduced up to 60% by food

Onset: 3 weeks

Duration: 12-30 weeks (multiple doses)

 

Distribution

Protein bound: 78%

Vd: 28 L (exclusive of bone)

 

Metabolism

Not metabolized

 

Elimination

Half-life: Up to 10 years in bone (terminal)

Excretion: Urine 50%, feces (unabsorbed drug)