Verify pregnancy status. Baseline studies and prehydration required. See Precautions and Monitor.
Do not exceed a 90-mg dose.
Moderate hypercalcemia (corrected serum calcium of 12 to 13.5 mg/dL):
One dose of 60 to 90 mg as an infusion.
Severe hypercalcemia (corrected serum calcium greater than 13.5 mg/dL):
One dose of 90 mg as an infusion. Serum calcium levels should fall into the normal range (8.5 to 10.5 mg/100 mL, corrected for serum albumin).
Experience is limited, but retreatment with the same dose may be considered if hypercalcemia is not fully corrected or recurs; wait at least 7 days from completion of first infusion to allow full response. Always used in conjunction with adequate hydration and appropriate testing. See Precautions/Monitor.
30 mg/day as an infusion for 3 consecutive days (total dose is 90 mg over 3 days). Selected patients have been retreated with the same dose when indicated. Experience limited. Prehydration required; see Precautions and Monitor.
Osteolytic bone lesions of multiple myeloma:
90 mg as an infusion once every 30 days. Optimal duration of therapy not known. Withhold dose if renal function has deteriorated; see Dose Adjustments, Precautions, and Monitor.
Osteolytic bone metastases of breast cancer:
90 mg as an infusion every 3 to 4 weeks. Optimum duration of therapy not known. Withhold dose if renal function has deteriorated; see Dose Adjustments, Precautions, and Monitor.
Accumulation of pamidronate in renally impaired patients is not anticipated if dosed on a monthly schedule. No experience with creatinine above 5 mg/100 mL (1 dL) or in severe hepatic disease.
■ See Precautions and Elderly.
Osteolytic bone lesions of multiple myeloma and osteolytic bone metastases of breast cancer:
Withhold dose if renal function has deteriorated. Renal deterioration is defined as an increase of 0.5 mg/dL in patients with a normal baseline creatinine or an increase of 1 mg/dL in patients with abnormal baseline creatinine. One study suggests that treatment should not be resumed until SCr has returned to within 10% of baseline value.
Reconstitute each 30- or 90-mg vial with 10 mL SWFI. Dissolve completely (3 or 9 mg/mL).
Further dilute a single dose in 1,000 mL NS, ½NS, or D5W. A minimum of 500 mL diluent may be used if absolutely necessary in patients with compromised cardiovascular status.
Further dilute a single daily dose in 500 mL NS, ½NS, or D5W.
Osteolytic bone lesions of multiple myeloma:
Further dilute each 90-mg dose in 500 mL NS, ½ NS, or D5W.
Osteolytic bone metastases of breast cancer:
Further dilute each 90-mg dose in 250 mL NS, ½ NS, or D5W.
Before reconstitution, store at CRT. After reconstitution, may be refrigerated for up to 24 hours. Stable after dilution for 24 hours at room temperature.
Should be given in a single intravenous solution and line separate from all other drugs, and do not mix with calcium-containing solutions (e.g., Ringer’s solutions).
Use of a microdrip (60 gtt/mL) or an infusion pump recommended for even distribution. Do not exceed recommended rate of infusion. Duration should be no less than 2 hours. Too-rapid infusion rate may lead to overdose, elevated BUN and creatinine levels, and renal tubular necrosis. Rate recommendations vary considerably. They are based on specific clinical trials for each diagnosis. In some trials a rate of up to 1 mg/min has been used with caution.
A 60-mg dose or 90-mg dose equally distributed over 2 to 24 hours. Longer infusion times (i.e., greater than 2 hours) may reduce the risk of renal toxicity, particularly in patients with pre-existing renal insufficiency.
A single dose over 4 hours.
Osteolytic bone lesions of multiple myeloma:
A single dose over 4 hours.
Osteolytic bone metastases of breast cancer:
A single dose over 2 hours.
A bisphosphonate hypocalcemic agent. Reduces serum calcium concentrations by inhibiting bone resorption. Binds to preformed bone surfaces and may block bone mineral dissolution. May also inhibit osteoclast activity. Effectively inhibits accelerated bone resorption resulting from osteoclast hyperactivity induced by various tumors. Does not inhibit bone formation and mineralization. Some reduction in calcium levels seen in 24 to 48 hours, and maximum response in 4 to 7 days. Rapidly adsorbed by bone. Is not metabolized. Half-life is approximately 21 to 35 hours. Slowly excreted in urine.
Treatment of moderate to severe hypercalcemia of malignancy in patients with or without bone metastasis, in conjunction with adequate hydration. Symptoms of hypercalcemia may include anorexia, bone pain, confusion, constipation, dehydration, depression, fatigue, lethargy, muscle weakness, nausea and vomiting, and polyuria. Severe dehydration may lead to renal insufficiency. With high levels of serum calcium, cardiac manifestations (e.g., bradycardia, cardiac arrest, ventricular arrhythmias) and neurologic symptoms (e.g., coma, seizures, and death) may occur.
■ Treatment of Paget’s disease.
■ Adjunct in treatment of osteolytic lesions of multiple myeloma and osteolytic bone metastases of breast cancer.
Prevention of bone loss associated with androgen deprivation therapy in prostate cancer.
Hypersensitivity to pamidronate or other bisphosphonates (e.g., alendronate, risedronate, zoledronic acid).
Calcium is bound to albumin. Total serum calcium levels in patients who have hypercalcemia of malignancy may not reflect the severity of the hypocalcemia because concomitant hypoalbuminemia is commonly present. Measurement with ionized calcium levels is preferred. If unavailable, all calcium measurement should be corrected for albumin to establish a basis for treatment and evaluation of treatment.
■ Mild or asymptomatic hypercalcemia will be treated with conservative measures (e.g., saline hydration, with or without diuretics [after correcting hypovolemia]). Consider patient’s cardiovascular status. Corticosteroids may be indicated if the underlying cancer is sensitive (e.g., hematologic cancers).
■ May be used adjunctively with chemotherapy, radiation, or surgery.
■ May cause renal toxicity. Deterioration in renal function progressing to renal failure has been reported and has occurred after the initial or a single dose of pamidronate. Patients with pre-existing renal impairment may be at increased risk for developing toxicity. Do not exceed dose of 90 mg.
■ Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates. The majority of cases have been in cancer patients. Risk factors include cancer, concomitant therapy (e.g., chemotherapy, radiotherapy, corticosteroids), and comorbid conditions (e.g., anemia, coagulopathies, infection, pre-existing oral disease). Literature and case reports suggest a higher frequency of ONJ based on tumor type (breast cancer, multiple myeloma) and dental status (dental extraction, periodontal disease, local trauma, including poorly fitting dentures). Cancer patients should maintain good oral hygiene. Consider dental exam and appropriate preventive dentistry before beginning therapy with bisphosphonates. Avoid invasive dental procedures during bisphosphonate therapy. Dental surgery may exacerbate ONJ in patients who develop ONJ while on bisphosphonate therapy.
■ Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported rarely. Onset of symptoms varied from one day to several months after beginning treatment with pamidronate. In most cases, pain resolves when pamidronate is discontinued; however, in some patients symptoms resolved slowly or persisted.
■ Atypical subtrochanteric and diaphyseal femoral fractures have been reported. May occur after minimal or no trauma. Risk may be increased in patients receiving concurrent glucocorticoids (e.g., dexamethasone, prednisone).
■ May be at risk for anemia, leukopenia, or thrombocytopenia; see Monitor.
■ Patients with a history of thyroid surgery may have relative hypoparathyroidism that may predispose them to hypocalcemia with pamidronate. Osteolytic bone lesions of multiple myeloma and osteolytic bone metastases of breast cancer: Patients being treated for multiple myeloma and bone metastases should have the dose withheld if renal function has deteriorated; see Dose Adjustments. Use is not recommended in patients with severe renal impairment being treated for bone metastases. See Monitor and Dose Adjustments. Limited information available on use in multiple myeloma patients with a CrCl less than 30 mL/min. In clinical trials, patients with a SCr above 3 mg/dL were excluded.
■ In the absence of hypercalcemia, patients with multiple myeloma or Paget’s disease of the bone or patients with predominantly lytic bone metastases who are at risk for calcium and vitamin D deficiency should be given oral calcium and vitamin D to reduce the risk of hypocalcemia.
Obtain baseline measurements of serum calcium (corrected for serum albumin), electrolytes, phosphate, magnesium, and creatinine and CBC with differential and hematocrit/hemoglobin. Monitor all closely as indicated by baseline results (may be daily). Serum phosphate levels will decrease and may require treatment.
■ Monitor renal function before each treatment; deterioration in renal function has been reported; see Precautions.
■ Monitor serum alkaline phosphatase during therapy for Paget’s disease.
■ Patients with cancer-related hypercalcemia are frequently dehydrated. Must be adequately hydrated orally and/or IV before treatment is initiated. Hydration with saline is preferred to facilitate renal excretion of calcium and to correct dehydration. A pretreatment urine output of 2 L/day is recommended. Maintain adequate hydration and urine output throughout treatment.
■ Avoid overhydration in patients with compromised cardiovascular status. Observe frequently for signs of fluid overload. Correct hypovolemia before using diuretics.
■ Monitor patients with pre-existing anemia, leukopenia, or thrombocytopenia very carefully during treatment and for the first 2 weeks following treatment.
■ Monitor for S/S of atypical femoral fractures that may occur with minimal or no trauma. Thigh or groin pain may be experienced weeks to months before a fracture appears. Fractures are often bilateral; examine both femurs. Osteolytic bone lesions of multiple myeloma: Adequately hydrate patients who have marked Bence-Jones proteinuria and dehydration before pamidronate infusion.
Regular visits and assessment of lab tests imperative.
■ Dietary restriction of calcium and vitamin D may be required.
■ Take only prescribed medications.
■ Report abdominal cramps, chills, confusion, fever, muscle spasms, sore throat, and/or any new medical problems promptly.
■ Report development of bone, joint, or muscle pain promptly. Onset of pain is variable.
■ Avoid pregnancy; use of effective birth control necessary during treatment and for an undetermined time after treatment; see prescribing information.
Category D: should not be used during pregnancy. May cause fetal harm.
■ Discontinue breast-feeding.
■ Safety for use in pediatric patients not established.
Response similar to that seen in younger patients.
■ Use with caution based on age-related impaired organ function and concomitant disease or drug therapy; monitor renal function closely. See Dose Adjustments.
■ Monitor fluid and electrolyte status carefully to avoid overhydration or electrolyte imbalance. Use of lower fluid volume may be required; see Dilution.
Use caution when administered with other potentially nephrotoxic drugs (e.g., aminoglycosides, cisplatin).
■ Effects may be antagonized by calcium-containing preparations or vitamin D; avoid use.
■ Concurrent use with thalidomide may increase risk of renal toxicity in patients with multiple myeloma.
Abdominal pain, anemia, anorexia, bone pain, confusion and visual hallucinations (sometimes in conjunction with electrolyte imbalance), constipation, fever (mild and transient), generalized pain, hypertension, hypocalcemia (abdominal cramps, confusion, muscle spasms), infusion site reaction (e.g., induration and pain on palpation, redness, swelling), musculoskeletal pain (bone, joint, and/or muscle pain), pruritus, rash, renal toxicity, seizures, urinary tract infections, vomiting. Fluid overload, hypokalemia, hypomagnesemia, and hypophosphatemia occur frequently with use of concurrent fluid and diuretics. Rare instances of hypersensitivity reactions, including anaphylaxis, angioedema, dyspnea, and hypotension, have occurred. Osteonecrosis (primarily of the jaw) has been reported (see Precautions). Anemia, leukopenia, and thrombocytopenia may occur.
Occurs less frequently with lower dose range (30 to 60 mg). Fever (high), hypocalcemia, hypotension, leukopenia or lymphopenia (fever, chills, sore throat), transient taste perversion. Elevated BUN and CrCl levels and renal tubular necrosis may occur with excessive dose or rate of administration.
Adult respiratory distress syndrome (ARDS); atypical subtrochanteric and diaphyseal femoral fractures; bone, joint, and muscle pain (may be severe and incapacitating); conjunctivitis; focal segmental glomerulosclerosis (including the collapsing variant); glomerulonephropathies; hematuria; hypernatremia; influenza-like symptoms; interstitial lung disease; nephrotic syndrome; orbital inflammation; reactivation of herpes simplex and herpes zoster; renal tubular disorders; tubulointerstitial nephritis.
Keep physician informed of side effects. Some may respond to symptomatic treatment. Magnesium, phosphorus, and potassium may require replacement if depletion too severe. If mild, all will probably return toward normal in 7 to 10 days. For asymptomatic or mild to moderate hypocalcemia (6.5 to 8 mg/100 mL corrected for serum albumin), short-term calcium therapy (e.g., calcium gluconate) may be indicated. Consider discontinuing pamidronate in patients who develop atypical fractures of the femur. Unknown if risk continues after stopping treatment. Discontinue drug for any symptoms of overdose. Monitor serum calcium and use vigorous IV hydration, with or without diuretics, for 2 to 3 days. Monitor intake and output to ensure adequacy and balance. Use short-term IV calcium therapy if indicated. High fever may respond to steroids. RBC transfusions may be required in anemia. Treat anaphylaxis and resuscitate as indicated.