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Pamidronate (Monograph)

Brand name: Aredia
Drug class: Bone Resorption Inhibitors
- Bone Resorption Inhibitors
VA class: HS900
Chemical name: (3-Amino-1-hydroxypropylidene)bisphosphonic acid disodium salt pentahydrate
Molecular formula: C3H9NNa2O7P2•5H2O
CAS number: 109552-15-0

Medically reviewed by Drugs.com on Jun 22, 2023. Written by ASHP.

Introduction

Synthetic bisphosphonate; bone resorption inhibitor.1 3 4 5 52 53

Uses for Pamidronate

Hypercalcemia Associated with Malignancy

Used in conjunction with achievement and maintenance of adequate hydration for the treatment of moderate to severe hypercalcemia associated with malignant neoplasms, with or without bone metastases.1 3 4 5 52 53

More conservative measures (e.g., hydration alone or combined with loop diuretics) generally used for treatment of mild or asymptomatic hypercalcemia.1 5 31 32 33 39 52 53 Corticosteroid therapy may be beneficial in hypercalcemia associated with hematological malignancies.1 52 53

Consider retreatment in patients with recurrent or refractory disease.1 52 53

Paget’s Disease of Bone

Treatment of moderate to severe Paget’s disease of bone (osteitis deformans)1 6 7 8 9 11 13 15 16 25 26 40 52 53 in symptomatic patients with multiple bone involvement [polyostotic] and elevated concentrations of serum alkaline phosphatase and urinary hydroxyproline.7 8 13 20

May prevent or slow progression of complications (e.g., deformities, arthritis, fractures, neurologic manifestations, spinal cord compression, heart failure) in patients with Paget’s disease of bone.11 26 40 May not reverse established complications (e.g., severe deformities, deafness).11 26 40

Treatment in patients refractory to calcitonin or etidronate disodium.8 9 11 13 16

Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma

Used as an adjunct to antineoplastic therapy for the treatment of osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma.1 20 29 52 53

Decreases the incidence and delays the development of bone-related complications (e.g., fractures or spinal cord compression, bone deterioration requiring radiotherapy or orthopedic surgery), and reduces bone pain and the need for supplemental analgesic therapy.1 23 24 27 52 53

Pamidronate Dosage and Administration

General

Hypercalcemia Associated with Malignancy

Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma

Paget’s Disease of Bone

Administration

IV Administration

Administer by IV infusion.1 3 4 5 8 11 14 16 20 23 24 26 27 29 40 52 53

Available as a lyophilized powder for injection1 53 and as an injection concentrate.52 53

Reconstitution

Reconstitute vial containing 30 or 90 mg of lyophilized pamidronate disodium with 10 mL of sterile water for injection to provide a solution containing 3 or 9 mg/mL, respectively.1 53

Allow the contents of the vial to dissolve completely before withdrawing dose.1 53

Dilution

Dilute reconstituted lyophilized drug or injection concentrate prior to administration.1 52 53

For treatment of hypercalcemia associated with malignancy, dilute the recommended daily dose in 1 L of 0.45 or 0.9% sodium chloride injection or 5% dextrose injection.1 52 53

For treatment of Paget’s disease of bone, dilute 30 mg in 500 mL of 0.45 or 0.9% sodium chloride injection or 5% dextrose injection.1 52 53

For treatment of osteolytic bone metastases of breast cancer, dilute 90 mg in 250 mL of 0.45 or 0.9% sodium chloride injection or 5% dextrose injection.1 52 53

For treatment of osteolytic lesions of multiple myeloma, dilute 90 mg in 500 mL of 0.45 or 0.9% sodium chloride injection or 5% dextrose injection.1 52 53

Rate of Administration

Longer infusions (i.e., >2 hours) may decrease the risk of adverse effects (e.g., infusion site reactions, renal impairment).1 6 17 52 53 (See Renal Effects under Cautions.)

For treatment of hypercalcemia associated with malignancy, infuse over 2–24 hours.1 52 53

For treatment of Paget’s disease of bone, infuse over a 4-hour period once daily for 3 consecutive days.1 52 53

For treatment of osteolytic bone metastases of breast cancer, infuse over a 2-hour period once every 3–4 weeks.1 52 53

For treatment of osteolytic lesions of multiple myeloma, infuse over a 4-hour period once monthly.1 52 53

Dosage

Available as pamidronate disodium; dosage is expressed in terms of the salt.1 52 53

Adults

Hypercalcemia Associated with Malignancy
Moderate Hypercalcemia
IV

60–90 mg as a single dose over 2–24 hours in those with albumin-corrected serum calcium concentration approximately 12–13.5 mg/dL.1 52 53

Consider retreatment if serum calcium concentrations do not return to normal or do not remain normal.1 52 53 In order to allow for full response to the initial dose, repeat the dose appropriate for the degree of hypercalcemia no sooner than 7 days after the initial dose.1 52 53

Severe Hypercalcemia
IV

90 mg as a single dose over 2–24 hours in those with albumin-corrected serum calcium concentration >13.5 mg/dL.1 52 53

Consider retreatment if serum calcium concentrations do not return to normal or remain normal.1 52 53 In order to allow for full response to the initial dose, repeat the dose appropriate for the degree of hypercalcemia no sooner than 7 days after the initial dose.1 52 53

Paget’s Disease of Bone
IV

Initially, 30 mg, administered as a 4-hour infusion, once daily on 3 consecutive days (total cumulative dose 90 mg for the course).1 52 53

Monitor periodically for recurrence of disease (e.g., increased serum alkaline phosphatase concentrations and urinary hydroxyproline); individualize the need for retreatment based on patient response.7 8 9 11 13 17 25 40 When clinically indicated, retreat with the same dosage that was required for initial treatment.1 52 53

Osteolytic Bone Metastases of Breast Cancer
IV

Initially, 90 mg, administered as a 2-hour infusion, given once every 3–4 weeks.1 52 53 Optimum duration of such therapy is not known, but has been used for up to at least 24 months in clinical studies.1 52 53

Osteolytic Bone Lesions of Multiple Myeloma
IV

Initially, 90 mg, administered as a 4-hour infusion, given once monthly.1 52 53 Optimum duration of therapy currently is not known, but monthly doses have been administered for up to at least 21 months in clinical studies.1 52 53

Prescribing Limits

Adults

IV

Maximum 90 mg as a single dose.1 52 53

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild to moderate hepatic impairment; not studied in patients with severe hepatic impairment.1 52 53

Renal Impairment

Withhold therapy in patients with bone metastases associated with solid tumors or with osteolytic lesions associated with multiple myeloma if renal function deteriorates (defined as an increase in Scr of at least 0.5 or 1 mg/dL in patients with normal [<1.4 mg/dL] or elevated [≥1.4 mg/dL] baseline Scr, respectively) during therapy; in clinical trials, pamidronate therapy was not resumed until Scr had returned to within 10% of baseline levels.1 52 53

Geriatric Patients

No specific dosage recommendations; however, select dosage cautiously, usually starting at the lower end of the dosage range, because of possible age-related decreases in hepatic, renal, or cardiac function and concomitant diseases and drug therapy.1 52 53

Cautions for Pamidronate

Contraindications

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity

May cause fetal harm; use not recommended in pregnant women, and women of childbearing potential should avoid conception during therapy.1 52 53 If patient becomes pregnant, apprise of potential fetal hazard.1 52 53

Renal Effects

Possible renal toxicity (e.g., deterioration of renal function, progression to renal failure and dialysis); may occur after initial or single dose of pamidronate.1 52 53

Focal segmental glomerulosclerosis (including collapsing variant) with or without nephrotic syndrome reported, particularly in patients with multiple myeloma or breast cancer; gradual improvement in some patients following drug discontinuance.1 52 53

Risk of renal toxicity may be greater in patients with impaired renal function.1 52 53

Monitor Scr prior to each treatment.1 52 53

May reduce the risk for renal toxicity by using the recommended duration of infusion (i.e., >2 hours), particularly in patients with preexisting renal insufficiency.1 52 53

General Precautions

Metabolic Effects

Asymptomatic hypophosphatemia,1 3 30 31 33 52 53 hypokalemia,1 52 53 hypomagnesemia,1 33 38 52 53 and hypocalcemia reported.1 3 9 11 30 33 52 53 Rarely, symptomatic hypocalcemia, including tetany, reported.1 52 53

Carefully monitor standard hypercalcemia-related metabolic parameters (e.g., serum concentrations of calcium, phosphate, magnesium, and potassium) following initiation of therapy.1 52 53 Institute short-term calcium and/or vitamin D therapy if hypocalcemia occurs.1 17 19 52 53

Adequately hydrate patients with hypercalcemia of malignancy throughout treatment.1 52 53 Avoid overhydration, especially in patients with potential for cardiac failure.1 52 53 Attempt to restore urine output to 2 L/day throughout treatment.1 52 53

Musculoskeletal Effects

Osteonecrosis and osteomyelitis of the jaw reported in cancer patients receiving bisphosphonates.1 41 42 43 44 45 46 47 52 53 Most patients were receiving IV bisphosphonates and concurrent chemotherapy, head and neck radiation therapy, and corticosteroids.1 46 47 52 53 Postmarketing experience and literature reports suggest 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).41 42 43 44 45 46 53

Good oral hygiene and a dental examination (panoramic jaw radiograph) with appropriate preventive dentistry recommended prior to treatment with bisphosphonates in patients with cancer.1 41 42 43 46 47 52 53 Avoid invasive dental procedures in such patients if possible during therapy.1 42 43 46 47 52 53

Severe, occasionally incapacitating bone, joint, and/or muscle pain reported infrequently.1 42 48 49 51 52 53 Time to onset of symptoms varied from 1 day to years after treatment initiation.1 42 48 51 52 53 Such pain generally improves following discontinuance of the drug but has recurred upon subsequent rechallenge in some patients.1 42 48 49 50 51 52 53

Hematologic Effects

Anemia, leukopenia, neutropenia, and thrombocytopenia reported.1 52 53 Monitor complete blood counts with differential and hematocrit and hemoglobin.1 52 53 Carefully monitor patients with preexisting anemia, leukopenia, or thrombocytopenia for the first 2 weeks after treatment initiation.1 52 53

Specific Populations

Pregnancy

Category D.1 52 53 (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Not known if pamidronate is distributed into milk.1 52 53 Use with caution in nursing women.1 52 53

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 2 52 53

Geriatric Use

No substantial differences in safety and efficacy relative to younger patients, but increased sensitivity cannot be ruled out.1 52 53 (See Geriatric Use under Dosage and Administration.)

Renal Impairment

Safety and efficacy not established in patients with severe renal impairment (Scr >3 mg/dL).1 52 53 Not recommended for use in patients with severe renal impairment and bone metastases.1 52 53 Carefully weigh possible benefits and risks of therapy in other patients with severe renal impairment.1 52 53 (See Renal Effects under Cautions.)

Common Adverse Effects

Hypercalcemia of malignancy: Infusion-site reactions (e.g., erythema, edema, induration, pain on palpation, thrombophlebitis), transient low-grade fever, hypokalemia, hypophosphatemia.1 3 9 10 16 20 22 30 33 52 53

Paget’s disease of bone: Arthrosis, bone pain, hypertension, headache.1 52 53

Osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma: Skeletal pain, nausea, anemia, fever, fatigue, vomiting, constipation, dyspnea, diarrhea, headache, anorexia, myalgia, coughing, dyspepsia, abdominal pain.1 52 53

Drug Interactions

Nephrotoxic Agents

Potential for increased risk of nephrotoxicity.1 52 53 Use concomitantly with caution.1 52 53

Specific Drugs

Drug

Interaction

Comments

Diuretics, loop

No effect on calcium-lowering effect of pamidronate1 52 53

Thalidomide

Increased risk of nephrotoxicity with concurrent use in patients with multiple myeloma1 52 53

Pamidronate Pharmacokinetics

Absorption

Onset

Hypercalcemia associated with malignancy: Reduction of serum calcium concentration usually is apparent within 1–3 days3 4 33 38 and generally is maximal within 5–7 days.3 4 38

Paget’s disease of bone: Onset of therapeutic response usually is evident within the first week.1 17 52 53 Symptomatic relief of bone pain usually is evident within 0.5–3 months after therapy.8 13 40 The median time to appreciable therapeutic response (≥50% decrease from baseline) for serum alkaline phosphatase was approximately 1 month (90-mg dose).1 52 53 Plateau at 5–12 months after therapy.7 8 9 13 17 25 40

Bone metastases of breast cancer: Decrease in bone pain usually is evident within 2 weeks.20

Duration

Hypercalcemia associated with malignancy: Normocalcemia persists for about 6–14 days following a single dose.1 3 30 33 38 52 53

Paget’s disease of bone: Reduction in marker of bone formation (decrease of serum alkaline phosphatase concentrations) persist from 1–372 days.1 9 11 13 14 15 16 40 53

Special Populations

In patients with hepatic impairment, increased mean AUC and peak plasma concentrations.1 53

Distribution

Extent

Distributed mainly to bones, liver, spleen, teeth, and tracheal cartilage in rats.1 52 53 Protracted binding of the drug to the bone mineral matrix.1 4 15 20 22 26 52 53

Pamidronate crosses the placenta in rats; not known whether distributed into human milk.1 52 53

Elimination

Metabolism

No evidence of metabolism.1 4 15 20 22 26 52 53

Elimination Route

Urinary excretion is the sole means of elimination.1 52 53

Half-life

Averages 28 hours.1 52 53 Rate of elimination from bone not determined.1 52 53

Special Populations

In cancer patients with renal impairment, decreased clearance compared with cancer patients without renal impairment.1 52 53 Accumulation of pamidronate not anticipated when recommended dose is repeated on a monthly basis;1 52 53 however, limited pharmacokinetic data exist in patients with Clcr <30 mL/minute.1 52 53

In patients with hepatic impairment, decreased plasma clearance.1 52 53 Not thought to be clinically relevant.1 52 53

Stability

Storage

Parenteral

Powder for Injection

≤30°C or 20–25°C depending on manufacturer; consult manufacturers’ labelings.1 53

Store vials of reconstituted solution at 2–8°C for up to 24 hours.1 53

Injection Concentrate

20–25°C or below 25°C depending on manufacturer; consult manufacturers’ labelings.52 53

Compatibility

Do not mix with other drugs.1 52 53

Solution Compatibility1 52 53

Compatible

Dextrose 5% in water

Sodium chloride 0.45 or 0.9%

Incompatible

Ringer’s injection, lactated

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Pamidronate Disodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

30 mg*

Aredia

Novartis

Pamidronate Disodium for Injection

90 mg*

Aredia

Novartis

Pamidronate Disodium for Injection

Injection, for IV infusion

30 mg*

Pamidronate Disodium Injection

60 mg*

Pamidronate Disodium Injection

90 mg*

Pamidronate Disodium Injection

AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 2, 2012. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

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