Breast cancer, osteolytic bone metastases: IV: 90 mg over at least 2 hours once every 3 or 4 weeks (maximum: 90 mg per dose) (ASCO/CCO [Van Poznak 2017]).
Hypercalcemia of malignancy (albumin-corrected serum calcium ≥12 mg/dL [≥3 mmol/L]) (alternative agent):
Note: May also be used at the same doses for treatment of hypercalcemia due to excessive bone resorption from other causes (eg, granulomatous diseases, hyperparathyroidism, vitamin D intoxication) (Minisola 2015; Shane 2022). Asymptomatic or mildly symptomatic patients with chronic hypercalcemia may not require immediate treatment unless albumin-corrected serum calcium level is >14 mg/dL (>3.5 mmol/L) (Shane 2022).
Albumin-corrected serum calcium level 12 to 13.5 mg/dL (3 to 3.4 mmol/L) and symptomatic: IV: 60 to 90 mg as a single dose over 2 to 24 hours (maximum: 90 mg per dose).
Albumin-corrected serum calcium level >13.5 mg/dL (>3.4 mmol/L): IV: 90 mg as a single dose over 2 to 24 hours (maximum: 90 mg per dose).
Re-treatment: IV: May re-treat at the same dose 7 days after the initial treatment if serum calcium does not return to normal or does not remain normal.
Hyperparathyroidism (off-label use): IV: 15 to 90 mg as a single dose (maximum: 90 mg per dose) (Ammann 2003; Jansson 2004; Lu 2003); may be repeated every 1 to 2 months or when hypercalcemia recurs (Jansson 1991; Torregrosa 2003). The treatment period in clinical trials was up to 1 year (Torregrosa 2003).
Multiple myeloma, osteolytic bone lesions: IV: 90 mg over 4 hours once monthly:
Lytic bone disease: American Society of Clinical Oncology (ASCO) guidelines: 90 mg over at least 2 hours once every 3 to 4 weeks for up to 2 years (maximum: 90 mg per dose); less frequent dosing (eg, once every 3 months) may be considered in patients with stable/responsive disease (patients with no active disease and are on maintenance therapy); discontinue after 2 years in patients with responsive and/or stable disease; resume therapy upon relapse with new-onset skeletal-related events (ASCO [Anderson 2018]).
Newly diagnosed, symptomatic (off-label dose): 30 mg over 2.5 hours once monthly for at least 3 years (Gimsing 2010).
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.
Prevention of androgen deprivation-induced osteoporosis (off-label use): Males: IV: 60 mg over 2 hours once every 3 months (Smith 2001).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: There are only limited pharmacokinetic data in patients with CrCl <30 mL/minute.
Dosing adjustment in patients with kidney impairment prior to initiating pamidronate treatment:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute or SCr >3 mg/dL:
Breast cancer, osteolytic bone metastases: Use is not recommended (manufacturer's labeling).
Multiple myeloma (and extensive bone disease): 90 mg (or consider a reduced initial dose) over 4 to 6 hours (ASCO [Anderson 2018]) once every 3 to 4 weeks.
Other indications: Clinical judgement should determine whether the potential benefit outweighs the potential risk (manufacturer's labeling).
Hemodialysis, intermittent (thrice weekly): Avoid use; consider alternative agents. Limited data suggests that reduced pamidronate doses (30 to 60 mg) with slower infusion rates (over 4 to 6 hours) may be considered when other agents are not available (Davenport 1993; Mahmoud 2018; Torregrosa 2003; Trimarchi 2006); use with caution and only when potential benefits outweigh risks.
Peritoneal dialysis: Avoid use; consider alternative agents. Limited data suggests that reduced pamidronate doses (30 to 60 mg) (Davenport 1993) may be considered when other agents are not available. Prolonged infusion (over 4 to 6 hours) should be considered as well (expert opinion). Monitor closely; nephrotoxicity is a concern as this patient population often has residual kidney function (Marrόn 2008; Woo 2011). Use with caution and only if potential benefit outweighs the potential risk (expert opinion).
Dosing adjustment in patients who develop renal toxicity during pamidronate therapy:
Osteolytic bone lesions/metastases (manufacturer's labeling): Treatment should be withheld for deterioration in renal function (increase of SCr ≥0.5 mg/dL in patients with normal baseline [SCr <1.4 mg/dL] or ≥1 mg/dL in patients with abnormal baseline [SCr ≥1.4 mg/dL]). Resumption of therapy may be considered when serum creatinine returns to within 10% of baseline.
Multiple myeloma: American Society of Clinical Oncology (ASCO) guidelines (ASCO [Anderson 2018]):
Renal deterioration without an apparent cause: Withhold therapy; may resume at the prior dose when renal function returns to within 10% of baseline.
Unexplained albuminuria >500 mg/24 hours: Withhold dose until returns to baseline, then recheck every 3 to 4 weeks; consider reinitiating at a dose not to exceed 90 mg every 4 weeks and with a longer infusion time of at least 4 hours.
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
(For additional information see "Pamidronate: Pediatric drug information")
Note: Due to increased risk of nephrotoxicity, single doses should not exceed 90 mg.
Hypercalcemia: Limited data available: Children and Adolescents: Dosing based on several case reports and retrospective studies for treatment of hypercalcemia due to malignancy and/or immobility. Administer as a single infusion. Retreatment may be necessary if serum calcium does not return to normal or does not remain normal after initial treatment; reported interval for multiple doses is ≥24 hours.
Initial treatment: IV: 0.5 to 1 mg/kg; maximum dose: 90 mg (Kerdudo 2005; Kutluk 1999; Lteif 1998; Young 1998)
Severe, life-threatening: IV: 1.5 to 2 mg/kg; maximum dose: 90 mg; in one case report, a higher dose of 4 mg/kg was used to treat a serum calcium concentration of 18.9 mg/dL associated with bone metastases in a 4-year old child with non-Hodgkin lymphoma (Kerdudo 2005; Kutluk 1997; Kutluk 1999)
Osteogenesis imperfecta: Limited data available: Note: Reported dosing regimens variable (ie, weight-directed vs BSA-directed); duration of treatment has not been established; however, the most benefit has been shown to occur in the first 2 to 4 years of treatment (Rauch 2006).
Weight-directed dosing (Rauch 2003; Zietlin 2003):
Infants and Children <2 years: IV: Initial: 0.25 mg/kg once on day 1, then 0.5 mg/kg/dose daily days 2 and 3 of the first cycle, then 0.5 mg/kg/dose once daily for 3 days for subsequent cycles; cycles are repeated every 2 months for a total yearly dose of 9 mg/kg
Children 2 to 3 years: IV: Initial: 0.38 mg/kg once on day 1, then 0.75 mg/kg/dose daily days 2 and 3 of the first cycle, then 0.75 mg/kg/dose once daily for 3 days for subsequent cycles; cycles are repeated every 3 months for a total yearly dose of 9 mg/kg
Children >3 years and Adolescents: IV: Initial: 0.5 mg/kg once on day 1, then 1 mg/kg/dose daily days 2 and 3 of the first cycle, then 1 mg/kg/dose once daily for 3 days for subsequent cycles; cycles are repeated every 4 months for a total yearly dose of 9 mg/kg
BSA-directed dosing: Infants, Children, and Adolescents: IV: Initial: 10 mg/m2/dose once a month for 3 months, then increase to 20 mg/m2/dose once a month for 3 months, then increase to 30 mg/m2/dose once a month for subsequent doses; maximum dose: 40 mg/m2/dose was used in six patients after 1-2 years due to skeletal pain and less bone mineral gain; improvements in mobility and vertebral height was noted in patients who received this regimen for 3 to 6 years (n=11, median age at initiation of therapy: 3.6 months, range: 3 to 13 months) (Astrom 2007); another study used the same dosing in 14 prepubescent patients with mild disease (Heino 2011)
Osteopenia associated with cerebral palsy (nonambulatory): Limited data available; dosing regimens variable: Children and Adolescents: IV: Initial: 1 mg/kg/dose daily for 3 days; administer every 3 to 4 months; minimum dose: 15 mg; maximum dose: 35 mg. Dosing based on two trials; the first included 14 pediatric patients (age range: 6 to 16 years, treatment group: n=7), and reported an increase in bone mineral density; therapy was used in combination with calcium and vitamin D supplementation (Henderson 2002). In the other trial (n=25, age range: 3 to 19 years), a decreased incidence of fractures was noted after 1 year of therapy (Bachrach 2010). A lower dose was used in a trial of 23 pediatric patients (age range: 4 to 17 years); the initial dose was 0.37 mg/kg on day 1, followed by 0.75 mg/kg on day 2, then 0.75 mg/kg/dose once daily for 2 days was used for subsequent cycles; cycles were repeated every 4 months for 1 year; maximum single dose: 45 mg (Plotkin 2006).
There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested for baseline or renal impairment during therapy.
There are no pediatric-specific recommendations. Based on experience in adult patients, no dosing adjustment recommended for mild to moderate hepatic impairment and for severe impairment, there are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing. Begin at lower end of adult dosing range.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as disodium:
Generic: 30 mg/10 mL (10 mL); 90 mg/10 mL (10 mL)
Solution, Intravenous, as disodium [preservative free]:
Generic: 6 mg/mL (10 mL)
Solution Reconstituted, Intravenous, as disodium:
Generic: 30 mg (1 ea); 90 mg (1 ea)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as disodium:
Generic: 3 mg/mL (10 mL); 30 mg/10 mL (10 mL); 6 mg/mL (10 mL); 9 mg/mL (10 mL); 90 mg/10 mL (10 mL)
Solution Reconstituted, Intravenous:
Generic: 15 mg (1 ea)
IV: Infusion rate varies by indication. Longer infusion times (>2 hours) may reduce the risk for renal toxicity, especially in patients with preexisting renal insufficiency. The manufacturer recommends infusing over 2 to 24 hours for hypercalcemia of malignancy; over 2 hours for osteolytic bone lesions with metastatic breast cancer; and over 4 hours for Paget disease and for osteolytic bone lesions with multiple myeloma. ASCO guidelines for bisphosphonate use in multiple myeloma recommend infusing pamidronate over at least 2 hours; if therapy is withheld due to renal toxicity, infuse over at least 4 hours upon reintroduction of treatment after renal recovery; infuse over 4 to 6 hours in patients with preexisting severe renal impairment and extensive bone disease (ASCO [Anderson 2018]).
Parenteral: IV: Infusion rate varies by indication; longer infusion times (>2 hours) may reduce the risk for renal toxicity, especially in patients with preexisting renal insufficiency. In pediatric trials, infusion times were 4 hours for osteogenesis imperfecta, 3 to 4 hours for osteopenia from immobility, and 4 to 6 hours for hypercalcemia; a 24-hour infusion has also been used (Henderson 2002; Kerdudo 2005; Kutluk 1997; Lteif 1998; Rauch 2003; Young 1998).
Hazardous agent (NIOSH 2016 [group 3]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Hypercalcemia of malignancy: Treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases, in conjunction with adequate hydration.
Osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma: Treatment of osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma in conjunction with standard antineoplastic therapy.
Paget disease: Treatment of patients with moderate to severe Paget disease of bone.
Note: Guidelines recommend IV zoledronic acid as the preferred treatment (ES [Singer 2014]; Ralston 2019).
Bone loss associated with androgen deprivation treatment in prostate cancer (prevention); Hyperparathyroidism; Symptomatic bone metastases of thyroid cancer
Aredia may be confused with Adriamycin
Pamidronate may be confused with papaverine
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
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: <1%), upper respiratory tract infection (osteolytic bone metastases: 32%; hypercalcemia of malignancy: ≤3%), cough (osteolytic bone metastases: 25%), sinusitis (osteolytic bone metastases: 16%), pleural effusion (osteolytic bone metastases: 15%)
Miscellaneous: Fever (18% to 39%; may be transient, includes temperature increase of ≥1° C within 24 to 48 hours after treatment; Paget disease, includes temperature increase of ≥1° C within 48 hours after treatment, transient: ≤21%)
1% to 10%:
Cardiovascular: Atrial fibrillation (hypercalcemia of malignancy: ≤6%), hypertension (6%; Paget disease: ≥10%), syncope (hypercalcemia of malignancy: ≤6%), tachycardia (hypercalcemia of malignancy: ≤6%), atrial flutter (hypercalcemia of malignancy: ≤1%), cardiac failure (hypercalcemia of malignancy: ≤1%), edema (hypercalcemia of malignancy: ≤1%)
Central nervous system: Drowsiness (hypercalcemia of malignancy: ≤6%), psychosis (hypercalcemia of malignancy: ≤4%)
Endocrine & metabolic: Hypothyroidism (hypercalcemia of malignancy: ≤6%)
Gastrointestinal: Constipation (hypercalcemia of malignancy: ≤6%), gastrointestinal hemorrhage (hypercalcemia of malignancy: ≤6%), diarrhea (hypercalcemia of malignancy: ≤1%), stomatitis (hypercalcemia of malignancy: ≤1%)
Genitourinary: Uremia (hypercalcemia of malignancy: ≤4%)
Hematologic & oncologic: Leukopenia (hypercalcemia of malignancy: ≤4%), neutropenia (hypercalcemia of malignancy: ≤1%), thrombocytopenia (hypercalcemia of malignancy: ≤1%)
Infection: Candidiasis (hypercalcemia of malignancy: ≤6%)
Neuromuscular & skeletal: Arthropathy (Paget disease: ≥5%), back pain (Paget disease: ≥5%)
Renal: Renal insufficiency (osteolytic bone metastases, patients with normal baseline serum creatinine: 8%)
Respiratory: Rales (hypercalcemia of malignancy: ≤6%), rhinitis (hypercalcemia of malignancy: ≤6%)
Frequency not defined: Endocrine & metabolic: Hypervolemia (hypercalcemia of malignancy)
<1%, postmarketing, and/or case reports: Adult respiratory distress syndrome, anaphylactic shock, angioedema, confusion, conjunctivitis, electrolyte disturbance, episcleritis, femur fracture (subtrochanteric and diaphyseal), flu-like symptoms, focal segmental glomerulosclerosis (including collapsing variant), glomerulopathy, hematuria, herpes simplex infection (reactivation), herpes zoster (reactivation), hyperkalemia, hypernatremia, hypersensitivity reaction, hypotension, interstitial pulmonary disease, iritis, local inflammation (orbital), malaise, mineral abnormalities, nephrotic syndrome, osteonecrosis (primarily of the jaw), paresthesia, pruritus, renal failure, renal tubular disease, scleritis, skin rash, tetany, uveitis, visual hallucination
Clinically significant hypersensitivity to pamidronate, other bisphosphonates, or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling): Pregnancy; breastfeeding
Concerns related to adverse effects:
• 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). Some patients experience prodromal pain weeks or months before the fracture occurs. It is unclear if bisphosphonate therapy is the cause for these fractures; atypical femur fractures have also been reported in patients not taking bisphosphonates, and in patients receiving glucocorticoids. Patients receiving long-term (>3 to 5 years) bisphosphonate therapy may be at an increased risk (Adler 2016; NOF [Cosman 2014]). 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. Known risk factors for MRONJ include invasive dental procedures (eg, tooth extraction, dental implants, boney surgery), cancer diagnosis, concomitant therapy (eg, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, ill-fitting dentures, and comorbid disorders (anemia, coagulopathy, infection, preexisting dental or periodontal disease). Risk may increase with increased duration of bisphosphonate use and/or may be reported at a greater frequency based on tumor type (eg, advanced breast cancer, multiple myeloma). According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with bisphosphonates and other antiresorptive agents (denosumab), and antiangiogenic agents (eg, bevacizumab, sunitinib) used for the treatment of osteoporosis or malignancy; risk is significantly higher in cancer patients receiving antiresorptive therapy compared to patients receiving osteoporosis treatment (regardless of medication used or dosing schedule). MRONJ risk is also increased with monthly IV antiresorptive therapy compared to the minimal risk associated with oral bisphosphonate use, although risk appears to increase with oral bisphosphonates when duration of therapy exceeds 4 years. The AAOMS suggests that if medically permissible, initiation of IV bisphosphonates for cancer therapy should be delayed until optimal dental health is attained (if extractions are required, antiresorptive therapy should delayed until the extraction site has mucosalized or until after adequate osseous healing). Once IV bisphosphonate therapy is initiated for oncologic disease, procedures that involve direct osseous injury and placement of dental implants should be avoided. Patients developing ONJ during therapy should receive care by an oral surgeon (AAOMS [Ruggiero 2014]).
• 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.
Disease-related concerns:
• Breast cancer (metastatic): The American Society of Clinical Oncology (ASCO)/Cancer Care Ontario (CCO) updated guidelines on the role of bone-modifying agents (BMAs) in metastatic breast cancer patients (ASCO/CCO [Van Poznak 2017]). The guidelines recommend initiating a BMA (denosumab, pamidronate, zoledronic acid) in patients with metastatic breast cancer to the bone. One BMA is not recommended over another (evidence supporting one BMA over another is insufficient). The optimal duration of BMA therapy is not defined; however, the guidelines recommend continuing BMA therapy indefinitely. The analgesic effect of BMAs is modest and BMAs should not be used alone for pain management; supportive care, analgesics, adjunctive therapies, radiation therapy, surgery, and/or systemic anticancer therapy should be utilized. The ASCO/CCO guidelines are in alignment with prescribing information for dosing, renal dose adjustments, infusion times, prevention and management of osteonecrosis of the jaw, and monitoring of laboratory parameter recommendations.
• Hypoparathyroidism: Use caution with a history of thyroid surgery; patients may have relative hypoparathyroidism, predisposing them to pamidronate-related hypocalcemia.
• Multiple myeloma: Patients with Bence-Jones proteinuria and dehydration should be adequately hydrated prior to therapy. The American Society of Clinical Oncology (ASCO) has updated guidelines on bone-modifying agents (BMAs) in multiple myeloma (ASCO [Anderson 2018]). Bisphosphonate (pamidronate or zoledronic acid) therapy should be initiated in patients with radiographic or imaging evidence of lytic bone disease. Bisphosphonates may also be considered in patients with pain secondary to osteolytic disease and as adjunct therapy in patients receiving other interventions for fractures or impending fractures. The guidelines support utilizing IV bisphosphonates in patients with multiple myeloma and osteopenia (osteoporosis) but no radiographic evidence of lytic bone disease. Bisphosphonates are not recommended in patients with solitary plasmacytoma, smoldering (asymptomatic) or indolent myeloma with osteopenia in the absence of lytic bone disease. Bisphosphonates are also not recommended in monoclonal gammopathy of undetermined significance, unless osteopenia (osteoporosis) also is present. The guidelines recommend monthly treatment for a period of up to 2 years (less frequent dosing may be considered in patients with stable/responsive disease). After 2 years, consider discontinuing in responsive and stable patients, and reinitiate upon relapse if a new-onset skeletal-related event occurs. The ASCO guidelines are in alignment with the prescribing information for dosing, renal dose adjustments, infusion times, prevention and management of osteonecrosis of the jaw, and monitoring of laboratory parameter recommendations. According to the guidelines, in patients with extensive bone disease with existing severe renal disease (a serum creatinine >3 mg/dL or CrCl <30 mL/minute) pamidronate at a dose of 90 mg over 4 to 6 hours should be used (unless preexisting renal disease in which case a reduced initial dose should be considered). Monitor for albuminuria every 3 to 6 months; in patients with unexplained albuminuria >500 mg/24 hours, withhold the dose until level returns to baseline, then recheck every 3 to 4 weeks. Pamidronate may be reinitiated at a dose not to exceed 90 mg every 4 weeks with a longer infusion time of at least 4 hours.
• Renal impairment: Patients with serum creatinine >3 mg/dL were not studied in clinical trials; limited data are available in patients with CrCl <30 mL/minute. Evaluate serum creatinine prior to each treatment. For the treatment of bone metastases, use is not recommended in patients with severe renal impairment. With indications other than bone metastases, use clinical judgment to determine if benefits outweigh potential risks in patients with renal impairment.
Maintain adequate hydration with therapy (pediatric patients: 2 to 3 L/m2 [Kerdudo, 2005]) and urinary output during treatment; use with caution with other potentially nephrotoxic drugs.
Bisphosphonate therapy may not be appropriate for patients with mild osteogenesis imperfect; risk:benefit has not been established. Potential adverse effects in growing children include infusion reactions and effects on bone growth. Influenza-like reactions are common after the first dose occurring at 12 to 36 hours after the infusion and may include fever, rash, and vomiting; treatment with standard antipyretic therapy is usually adequate and symptoms do not generally recur after later doses. Increased height has been reported and theoretical effects of diminishing bone remodeling in a growing child may result in bone malformation or delayed recovery after fractures (Rauch, 2004).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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 of concern. Risk C: Monitor therapy
Thalidomide: May enhance the nephrotoxic effect of Pamidronate. Risk C: Monitor therapy
Bisphosphonates are incorporated into the bone matrix and gradually released over time. Because exposure prior to pregnancy may theoretically increase the risk of fetal harm, most sources recommend discontinuing bisphosphonate therapy in females of reproductive potential as early as possible prior to a planned pregnancy. Use in premenopausal females should be reserved for special circumstances when rapid bone loss is occurring; a bisphosphonate with the shortest half-life should then be used (Bhalla 2010; Pereira 2012; Stathopoulos 2011).
It is not known if bisphosphonates cross the placenta, but based on their lower molecular weight, fetal exposure is expected (Djokanovic 2008; Stathopoulos 2011).
Information related to the use of pamidronate in pregnancy is available from case reports and small retrospective studies (Baretić 2014; Green 2014; Koren 2018; Levy 2009; Stathopoulos 2011).
Bisphosphonates are incorporated into the bone matrix and gradually released over time. The amount available in the systemic circulation varies by drug, dose, and duration of therapy. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy (hypocalcemia, low birth weight, and decreased gestation have been observed in some case reports); however, available data have not shown that exposure to bisphosphonates during pregnancy significantly increases the risk of adverse fetal events (Djokanovic 2008; Green 2014; Levy 2009; Machairiotis 2019; Sokal 2019; Stathopoulos 2011). Exposed infants should be monitored for hypocalcemia after birth (Djokanovic 2008; Stathopoulos 2011).
It is not known if pamidronate is present in breast milk.
Pamidronate was not detected in the milk of a breastfeeding female receiving pamidronate 30 mg IV monthly (therapy started ~6 months postpartum). Following the first infusion, milk was pumped and collected for 0 to 24 hours and 25 to 48 hours and each day pooled for analysis. Pamidronate readings were below the limit of quantification (<0.4 micromole/L). During therapy, breast milk was pumped and discarded for the first 48 hours following each infusion prior to resuming breastfeeding. The infant was breastfed >80% of the time; adverse events were not observed in the breastfed infant (Simonoski 2000). Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
Multiple myeloma or metastatic bone lesions from solid tumors or Paget disease: Take adequate daily calcium and vitamin D supplement (if patient is not hypercalcemic).
Serum creatinine (prior to each treatment); serum electrolytes, including calcium, phosphate, magnesium, and potassium; CBC with differential; monitor for hypocalcemia for at least 2 weeks after therapy; dental exam and preventive dentistry prior to therapy for patients at risk of osteonecrosis, including all patients with cancer; patients with pre-existing anemia, leukopenia, or thrombocytopenia should be closely monitored during the first 2 weeks of treatment; in addition, monitor urine albumin every 3 to 6 months in patients with multiple myeloma.
Multiple myeloma: Monitor serum creatinine (prior to each dose), serum calcium (regularly); vitamin D levels (intermittently), spot urine sample for albuminuria (every 3 to 6 months; for unexplained albuminuria, obtain 24-hour urine collection to assess urinary albumin; reassess every 3 to 4 weeks with 24-hour urine collection for total protein and urine protein electrophoresis until renal function returns to baseline) (ASCO [Anderson 2018]).
Paget disease: Serum total alkaline phosphatase at 6 to 12 weeks for initial response to treatment (when bone turnover will have shown a substantial decline) and potentially at 6 months (maximal suppression of high bone turnover); following treatment completion, monitor at ~6 to 12-month intervals (Endocrine Society [Singer 2014]); monitoring more specific biochemical markers of bone turnover (eg, serum P1NP, NTX, serum beta-CTx) is generally only warranted in patients with Paget disease who have abnormal liver or biliary tract function or when early assessment of response to treatment is needed (eg, spinal compression, very active disease) (Endocrine Society [Singer 2014]); serum calcium and 25(OH)D; phosphorus and magnesium; symptoms of hypocalcemia, pain (posttreatment pain may not strictly correlate with increased biochemical markers [Ralston 2019])
Prostate cancer: Androgen deprivation therapy (ADT)-associated osteoporosis: Monitor BMD every 18 to 24 months (IOF [Cianferotti 2017]).
Oncology uses: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Pamidronate is a nitrogen-containing bisphosphonate; it inhibits bone resorption by disrupting osteoclast activity (Rogers 2011).
Onset of action:
Hypercalcemia of malignancy (HCM): Reduction of albumin-corrected serum calcium: Children: ~48 hours (Kerdudo 2005); Adults: ≤24 hours for decrease in albumin-corrected serum calcium; maximum effect: ≤7 days.
Paget disease: ~1 month for ≥50% decrease in serum alkaline phosphatase.
Maximum effect: Hypercalcemia of malignancy: ≤7 days.
Duration: HCM: 7 to 14 days; Paget disease: 1 to 372 days.
Absorption: Poorly from the GI tract.
Distribution: Binds to hydroxyapatite crystals in bone; distribution to bone is incompletely understood (Cremers 2019; manufacturer's labeling).
Metabolism: Not metabolized.
Half-life elimination: 28 ± 7 hours (plasma elimination); rate of elimination from bone has not been determined.
Excretion: Urine (exclusive route of elimination; 30% to 62% of dose as unchanged drug within 120 hours [remainder of dose retained in the body]; lower in patients with renal dysfunction).
Solution (Pamidronate Disodium Intravenous)
6 mg/mL (per mL): $4.09
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