Version July 2025
Hypercalcemia: Limited data available:
Note: Dosing based on case reports/series describing treatment of hypercalcemia, primarily associated with malignancy.
Children and Adolescents: Usual reported dose: 1 mg/kg/dose once; reported range: 0.5 to 2 mg/kg/dose; maximum dose: 90 mg/dose (Ref). Consider doses on the higher end of the range (eg, 1.5 to 2 mg/kg) for severe, symptomatic hypercalcemia (Ref). Repeat doses have been described; allow at least 24 hours prior to administering another dose; full effects may take 2 to 4 days following initial dose (Ref).
Osteogenesis imperfecta: Limited data available: Note: Reported dosing regimens variable, including frequency of cycles. 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 (Ref).
Weight-directed dosing:
Infants and Children <2 years: IV: Initial (first cycle): 0.25 mg/kg once on day 1, then 0.5 mg/kg/dose daily on days 2 and 3; subsequent cycles (starting 2 months after initial cycle): 0.5 mg/kg/dose once daily for 3 days every 2 months (Ref).
Children 2 to 3 years: IV: Initial (first cycle): 0.38 mg/kg once on day 1, then 0.75 mg/kg/dose daily on days 2 and 3; subsequent cycles (starting 3 months after initial cycle): 0.75 mg/kg/dose once daily for 3 days every 3 months (Ref).
Children >3 years and Adolescents: IV: Initial (first cycle): 0.5 mg/kg once on day 1, then 1 mg/kg/dose daily on days 2 and 3; subsequent cycles (starting 4 months after initial cycle): 1 mg/kg/dose once daily for 3 days every 4 months (Ref).
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) (Ref); another study used the same dosing in 14 prepubescent patients with mild disease (Ref).
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 (Ref). In the other trial (n=25, age range: 3 to 19 years), a decreased incidence of fractures was noted after 1 year of therapy (Ref). 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 (Ref).
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).
(For additional information see "Pamidronate: Drug information")
Breast cancer, osteolytic bone metastases: IV: 90 mg over at least 2 hours once every 3 or 4 weeks (maximum: 90 mg per dose). The optimal duration of bone-modifying agent (BMA) therapy is not defined; however, ASCO guidelines recommend continuing BMAs indefinitely (Ref).
Hypercalcemia of malignancy (albumin-corrected serum calcium ≥12 mg/dL [≥3 mmol/L]) (alternative agent):
Note: Vigorous saline hydration should be initiated with pamidronate therapy (Ref). 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) (Ref). 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) (Ref).
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.
Multiple myeloma, osteolytic bone lesions:
Note: For use in conjunction with standard multiple myeloma therapy (Ref). May consider pamidronate for any patient with active multiple myeloma requiring treatment (Ref), although some reserve pamidronate for only those with osteolytic lesions, osteoporosis, or osteopenia (Ref). Patients with Bence-Jones proteinuria and dehydration should be adequately hydrated prior to therapy (Ref). Avoid invasive dental procedures and consider temporarily interrupting therapy before and after dental extractions or invasive oral procedures (Ref).
IV: 90 mg over 4 hours once monthly (Ref).
Lytic bone disease: Guideline recommendations: 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 (Ref).
Newly diagnosed, symptomatic (off-label dose): 30 mg over 2.5 hours once monthly for at least 3 years (Ref).
Paget disease, moderate to severe (alternative agent): 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.
Prostate cancer, bone loss associated with androgen deprivation therapy, prevention (alternative agent) (off-label use):
Note: For use in patients without bone metastases treated long-term with androgen deprivation therapy who are at elevated risk of osteoporotic fractures (according to a risk assessment tool) (Ref).
IV: 60 mg over 2 hours once every 3 months (Ref). The optimal duration of therapy has not been established (Ref).
Thyroid carcinoma, symptomatic bone metastases (off-label use): IV: 90 mg over 2 hours once a month for 12 doses (Ref).
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:
Note: Longer infusion times (>2 hours) may reduce the risk for kidney toxicity, especially in patients with preexisting kidney impairment (Ref).
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 (Ref).
Multiple myeloma (and extensive bone disease): 90 mg (or consider a reduced initial dose) over 4 to 6 hours (Ref) once every 3 to 4 weeks.
Hypercalcemia of malignancy:
SCr ≤4.5 mg/dL: No dosage adjustment necessary (Ref).
SCr >4.5 mg/dL:Use not recommended unless benefit outweighs risk (Ref); these patients were excluded from clinical trials (Ref).
Other indications: Clinical judgement should determine whether the potential benefit outweighs the potential risk (Ref).
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 (Ref); 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) (Ref) may be considered when other agents are not available. Prolonged infusion (over 4 to 6 hours) should be considered as well (Ref). Monitor closely; nephrotoxicity is a concern as this patient population often has residual kidney function (Ref). Use with caution and only if potential benefit outweighs the potential risk (Ref).
Dosing adjustment in patients who develop kidney toxicity during pamidronate therapy:
Osteolytic bone lesions/metastases: Treatment should be withheld for deterioration in kidney 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 (Ref).
Multiple myeloma: American Society of Clinical Oncology guideline recommendations:
Kidney function deterioration without an apparent cause: Withhold therapy; may resume at the prior dose when kidney function returns to within 10% of baseline (Ref).
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 (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCXTP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Pamidronate is not metabolized and is eliminated exclusively by the kidney. Pharmacokinetic data in Child-Turcotte-Pugh class C is lacking but liver impairment is not expected to impact exposure (Ref).
Liver impairment prior to treatment initiation:
Child-Turcotte-Pugh class A to C: IV: No dosage adjustment necessary (Ref).
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]).
• 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. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate.
• Electrolyte abnormalities: Pamidronate has been associated with asymptomatic electrolyte abnormalities (including hypophosphatemia, hypokalemia, hypomagnesemia, and hypocalcemia). Rare cases of symptomatic hypocalcemia, including tetany, have been reported.
• Kidney function deterioration: Pamidronate has been associated with kidney function deterioration, progressing to kidney failure and dialysis; kidney function deterioration may occur following the initial or single doses. Glomerulosclerosis (focal segmental), with or without nephrotic syndrome, has also been reported.
• 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 patients with cancer 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]).
Disease-related concerns:
• Hypoparathyroidism: Use caution with a history of thyroid surgery; patients may have relative hypoparathyroidism, predisposing them to pamidronate-related hypocalcemia.
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).
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)
Yes
Solution (Pamidronate Disodium Intravenous)
6 mg/mL (per mL): $5.45
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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)
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 (Ref).
IV: Infusion rate varies by indication. Longer infusion times (>2 hours) may reduce the risk for kidney toxicity, especially in patients with preexisting 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 (Ref). ASCO guidelines for bisphosphonate use in multiple myeloma recommend infusing pamidronate over at least 2 hours; if therapy is withheld due to kidney toxicity, infuse over at least 4 hours upon reintroduction of treatment after kidney function recovery; infuse over 4 to 6 hours in patients with preexisting severe kidney function impairment and extensive bone disease (Ref).
Hazardous agent (NIOSH 2024 [table 2]).
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 2023; NIOSH 2024; 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.
Vials, lyophilized powder for reconstitution: Store at 20°C to 25°C (68°F to 77°F). The reconstituted solution is stable for 24 hours stored under refrigeration at 2°C to 8°C (36°F to 46°F). The diluted solution for infusion is stable at room temperature for up to 24 hours.
Vials, in solution: Store at 20°C to 25°C (68°F to 77°F). The diluted solution for infusion is stable at room temperature for up to 24 hours.
Treatment of moderate or severe hypercalcemia associated with malignancy with or without bone metastases (in conjunction with adequate hydration); treatment of osteolytic bone lesions associated with multiple myeloma or metastatic breast cancer; treatment of moderate to severe Paget's disease of bone (All indications: FDA approved in adults); has also been used in the treatment of osteogenesis imperfecta and osteopenia in cerebral palsy patients
Aredia may be confused with Adriamycin
Pamidronate may be confused with papaverine
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
Aminoglycosides: May increase hypocalcemic effects of Bisphosphonate Derivatives. Aminoglycosides may increase nephrotoxic effects of Bisphosphonate Derivatives. Risk C: Monitor
Angiogenesis Inhibitors (Systemic): May increase adverse/toxic effects of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: Monitor
Capecitabine: Bisphosphonate Derivatives may increase nephrotoxic effects of Capecitabine. Risk C: Monitor
Deferasirox: Bisphosphonate Derivatives may increase adverse/toxic effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease therapeutic effects of Bisphosphonate Derivatives. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May increase adverse/toxic effects of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor
Palopegteriparatide: Bisphosphonate Derivatives may decrease therapeutic effects of Palopegteriparatide. Bisphosphonate Derivatives may increase therapeutic effects of Palopegteriparatide. Risk C: Monitor
Thalidomide: May increase nephrotoxic effects of Pamidronate. Risk C: Monitor
Multiple myeloma or metastatic bone lesions from solid tumors or Paget disease: Administer adequate daily calcium and vitamin D supplement (if patient is not hypercalcemic).
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 patients who could become pregnant as early as possible prior to a planned pregnancy. Use in premenopausal patients 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).
Monitor serum creatinine prior to each dose; monitor serum calcium, phosphate, potassium, and magnesium; monitor for hypocalcemia for at least 2 weeks after therapy; patients with pre-existing anemia, leukopenia, or thrombocytopenia should have hemoglobin, hematocrit, and CBC with differential monitored closely, particularly in the first 2 weeks following treatment; dental exam and preventative dentistry prior to therapy for patients at risk for osteonecrosis.
Additional indication-specific monitoring:
Osteogenesis imperfecta: In pediatric trials, motor milestones, ambulation assessment, total body length, sitting height, and arm span were recorded every 6 months. Bone density was measured every 6 months. Conventional x-rays were obtained once yearly (Heino 2011). Urinary excretion of calcium, alkaline phosphatase, and other bone-related chemistries were also monitored.
Osteopenia associated with cerebral palsy: In pediatric trials, bone mineral density, number and location of fractures, conventional x-rays, serum vitamin D concentrations, alkaline phosphatase, and other bone related chemistries were monitored (Bachrach 2010; Henderson 2002; Plotkin 2006).
Pamidronate is a nitrogen-containing bisphosphonate; it inhibits bone resorption by disrupting osteoclast activity (Rogers 2011).
Onset of action:
Hypercalcemia of malignancy: Reduction of albumin-corrected serum calcium: Children: ~48 hours (Kerdudo 2005); Adults: ≤24 hours for decrease in albumin-corrected serum calcium.
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 kidney dysfunction).
