etidronate (Rx)

1-10%

Convulsion

Fever

Hypocalcemia

Hypomagnesemia

Hypophosphatemia

Bone pain

Abnormal renal function

Frequency Not Defined

Amnesia

Confusion

Depression

Hallucination

Headache

Paresthesias

Alopecia

Rash

Altered taste

Gastritis

Glossitis

Hypocalcemia

Hypersensitivity reactions

Arthropathy

Fracture

Leg cramps

Nephrotoxicity

Renal insufficiency

Rare

• Esophageal cancer
• Peptic ulcer disease exacerbation
• Agranulocytosis
• Asthma exacerbation

Post-Marketing Reports

Skin: Alopecia

Hypersensitivity reactions, including angioedema, follicular eruption, macular rash, maculopapular rash, pruritus, epidermal necrolysis, Stevens-Johnson syndrome, and urticaria

Neuropsychiatric: Amnesia, confusion, depression, and hallucinations

Neurology: Paresthesias

Musculoskeletal: Arthropathies, including arthralgia and arthritis; bone fracture; osteomalacia

Hematology: Rare reports of agranulocytosis, pancytopenia, and a report of leukopenia with recurrence on rechallenge

Pulmonary: Exacerbation of asthma

Gastrointestinal: Exacerbation of existing peptic ulcer disease including perforation; esophagitis, glossitis

Contraindications

Osteomalacia

Hypersensitivity

Esophagus abnormalities (eg, stricture, achalasia) that delay esophageal emptying

Cautions

Enterocolitis, renal impairment

May cause local irritation of upper GI mucosa

Potentially causes severe esophagitis, esophageal ulcers and erosions

Ensure adequate intake of calcium, vitamin D

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

Risk of severe bone, joint and/or muscle pain

At higher doses both resorption inhibition and bone growth inhibition increases

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

• Conflicting findings exist from studies evaluating the risk of esophageal cancer with oral bisphosphonates
• Esophagitis and other esophageal events have been reported, particularly in patients who do not follow the specific directions for use of oral bisphosphonates (eg, sit up or stand after administration, take with full glass of water)
• An ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of cancer of the esophagus is currently being conducted by the FDA
• The FDA has not concluded that taking an oral bisphosphonate drug increases the risk of esophageal cancer
• There are insufficient data to recommend endoscopic screening of asymptomatic patients
• FDA will continue to evaluate all available data supporting the safety and effectiveness of bisphosphonate drugs and will update the public when more information becomes available
• 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 Category: C

Lactation: excretion in milk unknown; 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.

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.

Pharmacokinetics

Half-Life elimination: 1-6 hr (PO)

Onset: Within 1-3 months of treatment

Duration: Effect can persist up to 12 months without continuous treatment

Bioavailability: 3%

Vd: 1.37 L/kg

Metabolism: None

Excretion: Primarily unchanged in urine, unabsorbed drug excreted in feces