Pamidronate Disodium (pamidronate disodium)

The manufacturers state that safety and efficacy of pamidronate in children younger than 18 years of age have not been established.

Pamidronate should not be used in pregnant women; women of childbearing potential should avoid conception during drug therapy since the drug may cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions: Warning/Precautions, in Zoledronic Acid 92:24.)

Standard laboratory and clinical parameters of renal function (including serum creatinine) should be monitored prior to each treatment in patients receiving pamidronate therapy. Complete blood counts with differential and hematocrit/hemoglobin and standard hypercalcemia-related metabolic parameters, including serum concentrations of calcium, phosphate, magnesium, and potassium, also should be monitored carefully following initiation of pamidronate therapy. Cases of asymptomatic hypophosphatemia, hypokalemia, hypomagnesemia, and hypocalcemia have been reported in 12, 7, 11, and 5-12% of patients, respectively, receiving the drug in clinical studies. Symptomatic hypocalcemia, including tetany, has been reported rarely. If hypocalcemia occurs, short-term calcium and/or vitamin D therapy may be necessary. In patients with Paget's disease of bone treated with 30 mg of pamidronate disodium once daily for 3 consecutive days, serum calcium concentrations declined to less than 8 mg/dL in 17% of patients in clinical studies. Infusion-site reactions (e.g., erythema, edema, induration, pain on palpation, thrombophlebitis) and transient low-grade fever occur commonly with IV infusion of pamidronate.

Osteonecrosis and osteomyelitis of the jaw have been reported in patients receiving bisphosphonates. Most instances of osteonecrosis of the jaw have been observed during IV bisphosphonate therapy, but some patients have experienced this adverse effect during oral bisphosphonate therapy. Most of these patients had neoplasms and were receiving concurrent chemotherapy, head and neck radiation therapy, and corticosteroids. Postmarketing experience and literature reports suggest a greater frequency of cases associated with tumor type (advanced breast cancer, multiple myeloma) and dental status (e.g., tooth extraction, periodontal disease, poorly fitting dentures). Good oral hygiene and a dental examination (panoramic jaw radiograph) to detect dental and periodontal infections, with appropriate preventive dentistry (e.g., removal of abscessed and nonrestorable teeth and involved periodontal tissues, rehabilitation of salvageable dentition, dental prophylaxis and caries control, restorative dental care), are recommended prior to treatment with bisphosphonates in patients with cancer. Such patients should avoid invasive dental procedures if possible during treatment with bisphosphonates, as dental surgery may exacerbate the condition. (See Musculoskeletal Effects under Cautions: Warnings/Precautions, in Zoledronic Acid 92:24.)

Severe, occasionally incapacitating bone, joint, and/or muscle pain have been reported infrequently during postmarketing experience in patients receiving bisphosphonates, including pamidronate. The time to onset of symptoms varied from 1 day to years (mean onset about 3 months) after treatment initiation. Musculoskeletal pain has improved following discontinuance of the drug in most patients; however, some patients have reported slow or incomplete resolution of such pain. In some patients, musculoskeletal pain recurred upon subsequent rechallenge with the same drug or another bisphosphonate. (See Musculoskeletal Effects, under Cautions: Warnings/Precautions, in Zoledronic Acid 92:24.)

While data are conflicting, a possible increased risk of atrial fibrillation has been identified with use of bisphosphonates. (See Atrial Fibrillation, under Cautions: Warnings/Precautions, in Zoledronic Acid 92:24.)

When clinically indicated, patients can be retreated with pamidronate; however, the cumulative dose that may be administered in initial and subsequent courses of therapy with the drug remains to be established. In patients with hypercalcemia of malignancy, at least 7 days should elapse before retreatment is considered so that the full response to the previous dose can be assessed. In patients with Paget's disease of bone, pamidronate therapy can be repeated if clinically necessary. In patients with osteolytic bone metastases and lesions of cancer, prolonged therapy generally is required; the drug has been given once every 3-4 weeks for up to at least 21-24 months in clinical studies.

Renal impairment, which may progress to renal failure, has occurred following administration of bisphosphonates, including pamidronate. Focal segmental glomerulonephritis (including collapsing variant) with or without nephrotic syndrome has been reported in patients receiving pamidronate, particularly in patients with multiple myeloma or breast cancer; gradual improvement in some patients occurred following drug discontinuance. The risk of renal toxicity may be greater in patients with impaired renal function. Single doses of pamidronate disodium should not exceed 90 mg and the duration of IV infusion should be no less than 2 hours. Serum creatinine should be monitored in all patients receiving pamidronate, and possible deterioration in renal function must be assessed prior to administration of each dose. If patients with bone metastases associated with solid tumors or with osteolytic lesions associated with multiple myeloma experience a deterioration in renal function (defined as an increase in serum creatinine concentration of at least 0.5 or 1 mg/dL in patients with normal (less than 1.4 mg/dL) or elevated (1.4 mg/dL or greater) baseline serum creatinine concentrations, respectively) during therapy with pamidronate, the drug should be withheld; in clinical trials, pamidronate therapy was not resumed until serum creatinine concentrations had returned to within 10% of baseline concentrations.

Safety and efficacy of pamidronate in patients with severe renal impairment (serum creatinine concentration exceeding 5 mg/dL) remain to be established; only a few patients with multiple myeloma and serum creatinine concentrations of 3 mg/dL or greater have received the drug in clinical studies. Use of pamidronate in patients with bone metastases and severe renal impairment is not recommended by the manufacturer. In other indications, clinicians should carefully weigh the possible benefits and risks of pamidronate therapy in patients with such degrees of renal impairment. Cancer patients with renal impairment clear pamidronate more slowly than cancer patients without evidence of renal impairment, and renal clearance of the drug closely correlates with creatinine clearance. The manufacturer states that accumulation of pamidronate disodium in renally impaired patients is not anticipated when a dose of 90 mg is infused IV over 4 hours on a monthly basis.

Following administration of a single dose of pamidronate disodium (90 mg infused over 4 hours) in patients with neoplasms who were at risk for bone metastases and had mild to moderate hepatic dysfunction, peak blood concentrations and area under the blood concentration-time curve (AUC) were increased by 29 and 53%, respectively, and plasma clearance was decreased by 33% compared with values in patients with normal hepatic function. Such differences are not considered clinically important, and no dosage adjustments are necessary in patients with mild to moderate hepatic impairment. The pharmacokinetics of pamidronate have not been determined in patients with severe hepatic impairment.

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There are no contraindication interactions for this drug.

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• Aseptic necrosis of jaw bone

• Dehydration
• Hypovolemia
• Invasive dental procedure
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Periodontitis
• Pregnancy

• Hypocalcemia
• Hypokalemia
• Hypomagnesemia
• Hypophosphatemia
• Thyroid surgery

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More Frequent

• Body fluid retention
• Hypertension
• Hypocalcemia
• Hypokalemia
• Hypomagnesemia
• Pleural effusions

Less Frequent

• Drug-induced psychosis
• Edema
• Tachycardia

Rare or Very Rare

• Acute respiratory distress syndrome
• Anaphylaxis
• Angioedema
• Aseptic necrosis of jaw bone
• Atrial flutter
• Atypical femoral fracture
• Bone pain
• Focal segmental glomerulosclerosis
• Gastrointestinal hemorrhage
• Heart failure
• Hyperkalemia
• Hypotension
• Inflammation of orbit
• Interstitial lung disease
• Interstitial nephritis
• Iritis
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Leukopenia
• Neutropenic disorder
• Scleritis
• Syncope
• Thrombocytopenic disorder
• Uveitis

More Frequent

• Abdominal pain with cramps
• Anemia
• Anorexia
• Arthralgia
• Candidiasis
• Constipation
• Cough
• Dyspnea
• Fatigue
• Fever
• General weakness
• Granulocytopenic disorder
• Headache disorder
• Hypophosphatemia
• Injection site sequelae
• Insomnia
• Nausea
• Osteoarthritis
• Pain
• Rales
• Rhinitis
• Sinusitis
• Symptoms of anxiety
• Upper respiratory infection
• Urinary tract infection
• Vomiting

Less Frequent

• Chills
• Diarrhea
• Drowsy
• Dyspepsia
• Muscle rigidity
• Stomatitis
• Uremia

Rare or Very Rare

• Acute cognitive impairment
• Conjunctivitis
• Flu-like symptoms
• Hallucinations
• Hematuria
• Hypernatremia
• Hypothyroidism
• Malaise
• Myalgia
• Pruritus of skin
• Renal failure
• Skin rash

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