Pamidronate

Dosage Forms

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)

Pharmacology

Mechanism of Action

Pamidronate is a nitrogen-containing bisphosphonate; it inhibits bone resorption and decreases mineralization by disrupting osteoclast activity (Gralow 2009; Rogers 2011)

Pharmacokinetics/Pharmacodynamics

Absorption

Poorly from the GI tract

Distribution

38% to 70% over 120 hours

Metabolism

Not metabolized

Excretion

Biphasic; urine (30% to 62% as unchanged drug; lower in patients with renal dysfunction) within 120 hours

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 of Action

HCM: 7 to 14 days; Paget disease: 1 to 372 days

Half-Life Elimination

28 ± 7 hours

Use: Labeled Indications

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 (Endocrine Society [Singer 2014]; Ralston 2019).

Use: Off Label

Bone loss associated with androgen deprivation treatment in prostate cancer (prevention)b

Data from an open-label, randomized study supports the use of pamidronate in the prevention of bone loss associated with androgen deprivation treatment in prostate cancer. Pamidronate was found to prevent hip and lumbar spine bone loss Smith 2001.

Hyperparathyroidismc

The definitive treatment for primary hyperparathyroidism is parathyroidectomy; however, pamidronate may be useful in patients who are not candidates for surgery, who refuse surgery, or who would benefit from a delay in surgery. Pamidronate is not curative, and doses must be repeated to control hypercalcemia. In patients with secondary hyperparathyroidism, pamidronate may help control hypercalcemia and allow for more aggressive use of calcitriol.

Symptomatic bone metastases of thyroid cancerc

Data from a limited number of patients studied suggest that pamidronate may be beneficial for the treatment of symptomatic bone metastases of thyroid cancer Vitale 2001.

Contraindications

Clinically significant hypersensitivity to pamidronate, other bisphosphonates, or any component of the formulation

Canadian labeling: Additional contraindications (not in the US labeling): Pregnancy; breastfeeding

Dosage and Administration

Dosing: Adult

Note: Single doses should not exceed 90 mg.

Hypercalcemia of malignancy: IV:

Moderate cancer-related hypercalcemia (corrected serum calcium: 12 to 13.5 mg/dL): 60 to 90 mg, as a single dose over 2 to 24 hours

Severe cancer-related hypercalcemia (corrected serum calcium: >13.5 mg/dL): 90 mg, as a single dose over 2 to 24 hours

Re-treatment in patients who show an initial complete or partial response (allow at least 7 days to elapse prior to re-treatment): May re-treat at the same dose if serum calcium does not return to normal or does not remain normal after initial treatment.

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; 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)

Breast cancer, osteolytic bone metastases: IV: 90 mg over 2 hours once every 3 to 4 weeks

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

Hyperparathyroidism (off-label use): IV: 15 to 90 mg as a single 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).

Prevention of androgen deprivation-induced osteoporosis (off-label use): Males: IV: 60 mg over 2 hours once every 3 months (Smith 2001)

Dosing: Geriatric

Refer to adult dosing. Begin at lower end of adult dosing range.

Dosing: Pediatric

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).

Reconstitution

Powder for injection: Reconstitute by adding 10 mL of SWFI to each vial of lyophilized powder, the resulting solution will be 30 mg/10 mL or 90 mg/10 mL.

Pamidronate may be further diluted in 250 to 1000 mL of ¹/₂NS or NS or D5W. (The manufacturers recommend dilution in 1000 mL for hypercalcemia of malignancy, 500 mL for Paget disease and bone metastases of myeloma, and 250 mL for bone metastases of breast cancer.)

Administration

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]).

Dietary Considerations

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).

Storage

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 in D5W or NS at room temperature for up to 24 hours.

Solution for injection: Store at 20°C to 25°C (68°F to 77°F). The diluted solution for infusion is stable in D5W or NS at room temperature for up to 24 hours.

Drug Interactions

Aminoglycosides: May enhance the hypocalcemic effect of Bisphosphonate Derivatives. 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. 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. 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. Monitor therapy

Proton Pump Inhibitors: May diminish the therapeutic effect of Bisphosphonate Derivatives. Monitor therapy

Thalidomide: May enhance the nephrotoxic effect of Pamidronate. Monitor therapy

Test Interactions

Bisphosphonates may interfere with diagnostic imaging agents such as technetium-99m-diphosphonate in bone scans.

Adverse Reactions

>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

Warnings/Precautions

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.
• Hypercalcemia of malignancy (HCM): Adequate hydration is required during treatment (urine output ~2 L/day); avoid overhydration, especially in patients with heart failure.
• 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.

Monitoring Parameters

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 cancer patients; 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 multiple myeloma patients

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]).

Pregnancy

Pregnancy Risk Factor

D

Pregnancy Considerations

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; Sokal 2019; Stathopoulos 2011). Exposed infants should be monitored for hypocalcemia after birth (Djokanovic 2008; Stathopoulos 2011).

Until additional data are available, 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).

Patient Education

What is this drug used for?

• It is used to treat high calcium levels.
• It is used to treat Paget disease.
• It is used when treating some cancers.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Lack of appetite
• Constipation
• Back pain
• Fatigue
• Sweating a lot
• Trouble sleeping
• Cough
• Runny nose
• Stuffy nose
• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting.
• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.
• Severe abdominal pain
• Fast heartbeat
• Abnormal heartbeat
• Low thyroid level like constipation; difficulty handling heat or cold; memory problems; mood changes; or burning, numbness, or tingling feeling.
• Vomiting blood
• Black, red, or tarry stools
• Severe bone pain
• Severe joint pain
• Severe muscle pain
• Groin, hip, or thigh pain
• Severe dizziness
• Passing out
• Severe headache
• Severe loss of strength and energy
• Shortness of breath
• Edema
• Vision changes
• Jaw pain or edema
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.