No

Antidote; Bisphosphonate Derivative

Treatment of hypercalcemia associated with malignancy; treatment of osteolytic bone lesions associated with multiple myeloma or metastatic breast cancer; moderate to severe Paget's disease of bone

C

Previous hypersensitivity to pamidronate or other biphosphonates

Use caution in patients with renal impairment as nephropathy was seen in animal studies. However, in contrast to reports of renal failure with other biphosphonates, impairment of renal function has not been reported with pamidronate in studies to date. However, further experience is needed to assess the nephrotoxic potential with higher doses and prolonged administration. Use caution in patients who are pregnant or in the breast-feeding period; leukopenia has been observed with oral pamidronate and monitoring of white blood cell counts is suggested. Vein irritation and thrombophlebitis may occur with infusions. Has not been studied exclusively in the elderly; monitor serum electrolytes periodically since elderly are often receiving diuretics which can result in decreases in serum calcium, potassium, and magnesium.

1% to 10%:

Central nervous system: Malaise, fever, convulsions

Endocrine & metabolic: Hypomagnesemia, hypocalcemia, hypokalemia, fluid overload, hypophosphatemia

Gastrointestinal: GI symptoms, nausea, diarrhea, constipation, anorexia

Hepatic: Abnormal hepatic function

Neuromuscular & skeletal: Bone pain

Respiratory: Dyspnea

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

Symptoms of overdose include hypocalcemia, EKG changes, seizures, bleeding, paresthesia, carpopedal spasm, fever

Treat with I.V. calcium gluconate, general supportive care; fever and hypotension can be treated with corticosteroids

No data reported

Reconstitute by adding 10 mL of sterile water for injection to each 30 mg vial of lyophilized pamidronate disodium powder, the resulting solution will be 30 mg/10 mL

Pamidronate is incompatible with calcium-containing infusion solutions such as Ringer's injection

Pamidronate may be further diluted in 250-1000 mL of 0.45% or 0.9% sodium chloride or 5% dextrose; pamidronate should not be mixed with calcium-containing solutions (eg, Ringer's solution)

Pamidronate [reconstituted solution and infusion solution] is stable at room temperature and under refrigeration (36°F to 46°F or 2°C to 8°C) for 24 hours

A biphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors. Does not appear to produce any significant effects on renal tubular calcium handling and is poorly absorbed following oral administration (high oral doses have been reported effective); therefore, I.V. therapy is preferred.

Onset of effect: 24-48 hours

Maximum effect: 5-7 days

Absorption: Poorly from the GI tract; pharmacokinetic studies are lacking

Half-life, unmetabolized: 2.5 hours

Distribution half-life: 1.6 hours

Urinary (elimination) half-life: 2.5 hours

Bone half-life: 300 days

Elimination: Biphasic; ~50% excreted unchanged in urine within 72 hours

Drug must be diluted properly before administration and infused intravenously slowly (over at least 1 hour). Adults: I.V.:

Moderate cancer-related hypercalcemia (corrected serum calcium: 12-13 mg/dL): 60-90 mg given as a slow infusion over 2-24 hours

Severe cancer-related hypercalcemia (corrected serum calcium: >13.5 mg/dL): 90 mg as a slow infusion over 2-24 hours

A period of 7 days should elapse before the use of second course; repeat infusions every 2-3 weeks have been suggested, however, could be administered every 2-3 months according to the degree and of severity of hypercalcemia and/or the type of malignancy

Osteolytic bone lesions with multiple myeloma: 90 mg in 500 mL D₅W, 0.45% NaCl or 0.9% NaCl administered over 4 hours on a monthly basis

Osteolytic bone lesions with metastatic breast cancer: 90 mg in 250 mL D₅W, 0.45% NaCl or 0.9% NaCl administered over 2 hours, repeated every 3-4 weeks

Paget's disease: 30 mg in 500 mL 0.45% NaCl, 0.9% NaCl or D₅W administered over 4 hours for 3 consecutive days

Dosing adjustment in renal impairment: Adjustment is not necessary

Dilute in 1000 mL 5% dextrose, infuse over 24 hours

Serum electrolytes, monitor for hypocalcemia for at least 2 weeks after therapy; serum calcium, phosphate, magnesium, potassium, serum creatinine, CBC with differential

Calcium (total): Adults: 9.0-11.0 mg/dL (SI: 2.05-2.54 mmol/L), may slightly decrease with aging; Phosphorus: 2.5-4.5 mg/dL (SI: 0.81-1.45 mmol/L)

May cause drowsiness

May rarely cause leukopenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication can only be administered I.V. Avoid foods high in calcium or vitamins with minerals during infusion or for 2-3 hours after completion. You may experience nausea or vomiting (small frequent meals and good mouth care may help); or recurrent bone pain (consult prescriber for analgesic). Report unusual muscle twitching or spasms, severe diarrhea/constipation, or acute bone pain. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Powder for injection, lyophilized, as disodium: 30 mg, 60 mg, 90 mg

Body JJ, Pot M, Borkowski A, et al, "Dose/Response Study of Aminohydroxypropylidene Biphosphonate in Tumor-Associated Hypercalcemia," Am J Med, 1987, 82(5):957-63.

De S, Meyer P, and Crisp AJ, "Pamidronate and Uveitis," Br J Rheumatol, 1995, 34(5):479.

Drug Facts and Comparisons, St Louis, MO: JB Lippincott Co, 1992, 134f-134m.

Fitton A and McTavish D, "Pamidronate: A Review of Its Pharmacological Properties and Therapeutic Efficacy in Resorptive Bone Disease," Drugs, 1991, 41(2):289-318.

Glorieux FH, Bishop NH, Plotkin H, et al, "Cyclic Administration of Pamidronate in Children With Severe Osteogenesis Imperfecta," N Engl J Med, 1998, 339(14):947-52.

Kellihan MJ and Mangino PD, "Pamidronate," Ann Pharmacother, 1992, 26(10):1262-9.

Lteif AN and Zimmerman D, "Biphosphonates for Treatment of Childhood Hypercalcemia," Pediatrics, 1998, 102(4 Pt 1):990-3.

Ralston SH, Gallacher SJ, Patel U, et al, "Cancer-Associated Hypercalcemia: Morbidity and Mortality, Clinical Experience in 126 Treated Patients," Ann Intern Med, 1990, 112(7):499-504.