pamidronate disodium
Aredia

Available forms
Available by prescription only
Injection: 30 mg/vial, 90 mg/vial

Indications and dosages
 Moderate to severe hypercalcemia related to malignancy (with or without metastases). Adults: Dosage depends on severity of hypercalcemia. Serum calcium levels should be corrected for serum albumin. Corrected serum calcium (CCa) is calculated using the following formula:
 CCa (mg/dl) = serum Ca (mg/dl) + 0.8 (4 - serum albumin) (g/dl)
 Repeat doses shouldn’t be given sooner than 7 days to allow for full response to initial dose.
≡ Dosage adjustment. Patients with moderate hypercalcemia (CCa levels of 12 to 13.5 mg/dl) may receive 60 to 90 mg I.V. infusion as a single dose over 2 to 24 hours. Patients with severe hypercalcemia (CCa levels over 13.5 mg/dl) may receive 90 mg I.V. infusion over 2 to 24 hours.
 Paget’s disease. Adults: 30 mg I.V. daily over 4 hours for 3 consecutive days for total dose of 90 mg.
 Osteolytic bone lesions of multiple myeloma. Adults: 90 mg I.V. daily over 4 hours once monthly.
 Osteolytic bone lesions of breast cancer. Adults: 90 mg I.V. daily over 2 hours q 3 to 4 weeks.

Pharmacodynamics
Antihypercalcemic action: Inhibits bone resorption. Adsorbs to hydroxyapatite crystals in bone and may directly block dissolution of calcium phosphate. Apparently doesn’t inhibit bone formation or mineralization.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: About 50% to 60% of dose rapidly absorbed by bone; drug also taken up by kidneys, liver, spleen, teeth, and tracheal cartilage.
Metabolism: None.
Excretion: Excreted by kidneys; average of 51% of dose excreted in urine within 72 hours of administration.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other bisphosphonates such as etidronate. Use with extreme caution in patients with impaired renal function. Not recommended for patients with bone metastasis and severe renal dysfunction.

Interactions
Drug-drug. Calcium-containing solutions: Drug may form precipitate when mixed with solutions containing calcium. Don’t mix together.

Adverse reactions
CNS: seizures, fatigue, headache, somnolence, generalized pain, fever.
CV: atrial fibrillation, syncope, tachycardia, hypertension.
GI: abdominal pain, anorexia, constipation, nausea, vomiting, GI hemorrhage.
GU: renal dysfunction, renal failure.
Hematologic: leukopenia, thrombocytopenia, anemia.
Metabolic: hypophosphatemia, hypokalemia, hypomagnesemia, hypocalcemia.
Musculoskeletal: bone pain.
Skin: infusion-site reaction.

Effects on lab test results
• May decrease phosphate, potassium, magnesium, and calcium levels.
• May decrease hemoglobin, hematocrit, and WBC and platelet counts.

Overdose and treatment
Symptomatic hypocalcemia could result from overdose.
 Treat with I.V. calcium.

Special considerations
• Drug is of limited use in patients with multiple myeloma whose serum creatinine level is more than 3 mg/dl.
• Adequately hydrate patients with malignancy hypercalcemia or multiple myeloma with Bence-Jones proteinuria before starting therapy.
 ALERT Don’t exceed single doses of 90 mg to avoid renal dysfunction leading to renal failure.
• Reconstitute vial with 10 ml sterile water for injection. Once drug is completely dissolved, add to 250-ml (2-hour infusion), 500-ml (4-hour infusion), or 1,000-ml (up to 24-hour infusion) bag of half-normal or normal saline solution injection or D₅W. Don’t mix with infusion solutions that contain calcium, such as Ringer’s injection or lactated Ringer’s injection. Administer in single I.V. solution, in separate line from all other drugs. Inspect to rule out precipitates before administering.
• Injection solution is stable for 24 hours when refrigerated. Give only by I.V. infusion. Nephropathy may occur when drug is given as a bolus.
• Infusions longer than 2 hours may reduce the risk of renal toxicity, especially in patients with preexisting renal insufficiency.
• In patients with hypercalcemia of malignancy, at least 7 days between treatments is recommended.
• Because drug can cause electrolyte disturbances, careful monitoring of serum electrolytes is essential. Check serum creatinine level before each treatment. Short-term administration of calcium may be needed in patients with severe hypocalcemia. Also monitor hemoglobin, hematocrit, creatinine levels, CBC, and differential.
• Carefully monitor patients with anemia, leukopenia, or thrombocytopenia during first 2 weeks after therapy.
• Monitor patient’s temperature; 27% of patients have a slightly elevated temperature for 24 to 48 hours after therapy.
• Optimal duration of therapy isn’t known. Drug has been given for up to 24 months in clinical studies.
Pregnant patients
• Drug may cause fetal harm. Don’t use in pregnant women.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.

Patient education
• Explain use and administration of drug to patient and family.
• Tell women of child-bearing age to avoid pregnancy during therapy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use