No

Bisphosphonate Derivative

Symptomatic treatment of Paget's disease and heterotopic ossification due to spinal cord injury or after total hip replacement, hypercalcemia associated with malignancy

B (oral)/C (parenteral)

Patients with serum creatinine >5 mg/dL; hypersensitivity to biphosphonates

Use with caution in patients with restricted calcium and vitamin D intake; dosage modification required in renal impairment; I.V. form may be nephrotoxic and should be used with caution, if at all, in patients with impaired renal function (serum creatinine: 2.5-4.9 mg/dL)

1% to 10%:

Central nervous system: Fever, convulsions

Endocrine & metabolic: Hypophosphatemia, hypomagnesemia, fluid overload

Neuromuscular & skeletal: Bone pain

Respiratory: Dyspnea

<1%: Pain, angioedema, rash, abnormal taste, occult blood in stools, increased risk of fractures, nephrotoxicity, hypersensitivity reactions

Symptoms of overdose include diarrhea, nausea, vomiting, paresthesias, tetany, coma

Antidote is calcium

Foscarnet and plicamycin may have additive hypocalcemic effect

Store ampuls at room temperature and avoid excess heat (>40°C/104°F); intravenous solution diluted in greater than or equal to 250 mL normal saline is stable for 48 hours at room temperature or refrigerated

Decreases bone resorption by inhibiting osteocystic osteolysis; decreases mineral release and matrix or collagen breakdown in bone

Onset of therapeutic effect: Within 1-3 months of therapy

Duration: Can persist for 12 months without continuous therapy

Absorption: Dependent upon dose administered

Metabolism: Not metabolized

Elimination: As unchanged drug primarily in urine with unabsorbed drug being eliminated in feces

Adults: Oral formulation should be taken on an empty stomach 2 hours before any meal.

Initial: 5-10 mg/kg/day (not to exceed 6 months) or 11-20 mg/kg/day (not to exceed 3 months). Doses >10 mg/kg/day are not recommended.

Retreatment: Initiate only after etidronate-free period greater than or equal to 90 days. Monitor patients every 3-6 months. Retreatment regimens are the same as for initial treatment.

Heterotopic ossification: Oral:

Caused by spinal cord injury: 20 mg/kg/day for 2 weeks, then 10 mg/kg/day for 10 weeks; total treatment period: 12 weeks

Complicating total hip replacement: 20 mg/kg/day for 1 month preoperatively then 20 mg/kg/day for 3 months postoperatively; total treatment period is 4 months

Hypercalcemia associated with malignancy:

I.V. (dilute dose in at least 250 mL NS): 7.5 mg/kg/day for 3 days; there should be at least 7 days between courses of treatment

Oral: Start 20 mg/kg/day on the last day of infusion and continue for 30-90 days

Dosing adjustment in renal impairment:

S_cr 2.5-5 mg/dL: Use with caution

S_cr >5 mg/dL: Not recommended

Administer with water, black coffee, tea, or fruit juice on an empty stomach; avoid administering foods/supplements with calcium, iron, or magnesium within 2 hours of drug; maintain adequate intake of calcium and vitamin D

Dilute in a minimum volume of 250 mL normal saline; infuse over at least 2 hours

Serum calcium and phosphorous; serum creatinine and BUN

Calcium (total): Adults: 9.0-11.0 mg/dL

None reported

None reported

No information available to require special precautions

No effects or complications reported

Maintain adequate intake of calcium and vitamin D; take medicine on an empty stomach 2 hours before meals

Ensure adequate hydration

Injection: 50 mg/mL (6 mL)

Tablet: 200 mg, 400 mg

Gray RE, "Severe Reaction to Diphosphonate," BMJ, 1988, 297(6655):1042.

Storm T, Thamsborg G, Steiniche T, et al, "Effect of Intermittent Cyclical Etidronate Therapy on Bone Mass and Fracture Rate in Women With Postmenopausal Osteoporosis," N Engl J Med, 1990, 322(18):1265-71.

Watts NB, Harris ST, Genant HK, et al, "Intermittent Cyclical Etidronate Treatment of Postmenopausal Osteoporosis," N Engl J Med, 1990, 323(2):73-9.