Pamidia®

Breast cancer, osteolytic bone metastases: IV: 90 mg over at least 2 hours once every 3 or 4 weeks

Hypercalcemia of malignancy: IV: 60 to 90 mg, as a single dose over 2 to 24 hours.

Multiple myeloma, osteolytic bone lesions: IV: 90 mg over 4 hours once monthly

Paget disease (moderate to severe): IV: 30 mg over 4 hours once daily for 3 consecutive days (total dose = 90 mg); may re-treat at initial dose if clinically indicated.

Clinically significant hypersensitivity to pamidronate, other bisphosphonates, or any component of the formulation

Interactions:

Aminoglycosides: May enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy

Angiogenesis Inhibitors (Systemic): May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: Monitor therapy

Deferasirox: Bisphosphonate Derivatives may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are

Pregnancy and Lactation:

Use is contraindicated in pregnancy and lactation.

Warning and Precaution:

• Bone fractures: Atypical femur fractures (AFF) have been reported in patients receiving bisphosphonates. The fractures include subtrochanteric femur (bone just below the hip joint) and diaphyseal femur (long segment of the thigh bone). Patients receiving long-term (>3 to 5 years) bisphosphonate therapy may be at an increased risk. Patients presenting with thigh or groin pain with a history of receiving bisphosphonates should be evaluated for femur fracture. Consider interrupting bisphosphonate therapy in patients who develop a femoral shaft fracture; assess for fracture in the contralateral limb.
• Musculoskeletal pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Consider discontinuing therapy in patients who experience severe symptoms; symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy.
• Electrolyte abnormalities: Use has been associated with asymptomatic electrolyte abnormalities (including hypophosphatemia, hypokalemia, hypomagnesemia, and hypocalcemia). Rare cases of symptomatic hypocalcemia, including tetany, have been reported.
• Myelosuppression: Patients with preexisting anemia, leukopenia, or thrombocytopenia should be closely monitored during the first 2 weeks of treatment.
• Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ), has been reported in patients receiving bisphosphonates.
• Renal deterioration: Single pamidronate doses should not exceed 90 mg. Initial or single doses have been associated with renal deterioration, progressing to renal failure and dialysis. Glomerulosclerosis (focal segmental) with or without nephrotic syndrome has also been reported. Longer infusion times (>2 hours) may reduce the risk for renal toxicity, especially in patients with pre-existing renal insufficiency. Withhold pamidronate treatment (until renal function returns to baseline) in patients with evidence of renal deterioration

Adverse Reactions:

Central nervous system: Fatigue (osteolytic bone metastases: 32% to 40%; hypercalcemia of malignancy: ≤12%), headache (24% to 27%; Paget disease: ≥10%), insomnia (osteolytic bone metastases: 25%; hypercalcemia of malignancy: ≤1%), anxiety (osteolytic bone metastases: 18%), pain (≤13%)

Endocrine & metabolic: Hypophosphatemia (9% to 18%), hypokalemia (4% to 18%), hypocalcemia (1% to 17%), hypomagnesemia (4% to 12%)

Gastrointestinal: Nausea (osteolytic bone metastases: 64%; hypercalcemia of malignancy: ≤18%; Paget disease: ≥5%), vomiting (osteolytic bone metastases: 36% to 46%; hypercalcemia of malignancy: ≤4%), anorexia (osteolytic bone metastases: 31%; hypercalcemia of malignancy: ≤12%), abdominal pain (osteolytic bone metastases: 20% to 24%; hypercalcemia of malignancy: ≤1%), dyspepsia (osteolytic bone metastases: 18%; hypercalcemia of malignancy: ≤4%)

Genitourinary: Urinary tract infection (16% to 20%)

Hematologic & oncologic: Anemia (osteolytic bone metastases: 40% to 48%; hypercalcemia of malignancy: ≤6%), metastases (osteolytic bone metastases: 31%), granulocytopenia (osteolytic bone metastases: 20%)

 Local: Infusion site reaction (hypercalcemia of malignancy: ≤18%; includes erythema, induration, pain, and swelling)

Neuromuscular & skeletal: Myalgia (osteolytic bone metastases: 26%; hypercalcemia of malignancy: ≤1%), weakness (osteolytic bone metastases: 26%), ostealgia (5% to ≥15%), arthralgia (osteolytic bone metastases: 11% to 15%)

Renal: Increased serum creatinine (osteolytic bone metastases: 19%; mild)

Respiratory: Dyspnea (osteolytic bone metastases: 22% to 35%; other indications:

Storage:

Store below 30ºC and protect from freezing.