pamidronate disodium

Injectable Bisphosphonates

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

For intravenous infusion only.
The patient's renal function (i.e., serum creatinine) and hydration status should be assessed prior to each treatment with pamidronate.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Administer intravenously via slow IV infusion only. Dilute prior to administration.
 
Reconstitution/Dilution:
Reconstitute vial with 10 mL of sterile water for injection; the drug should be completely dissolved before solution is withdrawn. After reconstitution, store under refrigeration, 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours.
Pamidronate can be diluted in 0.45% or 0.9% Sodium Chloride Injection or Dextrose 5% for injection. Do not dilute in calcium-containing solutions such as Ringer's solution.
Hypercalcemia of malignancy: Dilute the recommended dose in 1000 mL of 0.45% or 0.9% Sodium Chloride Injection or Dextrose 5% for injection. The diluted solution is stable for up to 24 hours at room temperature.
Paget's Disease: Dilute the recommended dose in 500 mL of 0.45% or 0.9% Sodium Chloride Injection or Dextrose 5% for injection.
Osteolytic bone metastases of breast cancer: Dilute the recommended dose in 250 mL of 0.45% or 0.9% Sodium Chloride Injection or Dextrose 5% for injection.
Osteolytic bone lesions of multiple myeloma: Dilute the recommended dose in 500 mL of 0.45% or 0.9% Sodium Chloride Injection or Dextrose 5% for injection.
In children with osteogenesis imperfecta (off-label use): pamidronate has been diluted in 0.25% NS/D5W to a concentration of less than 0.12 mg/mL.
 
Intravenous infusion:
Due to risk of clinically significant renal toxicity, single doses should not exceed 90 mg and the duration of the IV infusion should be no less than 2 hours.
Administer in an IV line separate from all other drugs.
Hypercalcemia of malignancy: Infuse dose over 2 to 24 hours. A duration of infusion of more than 2 hours may decrease the risk for renal toxicity, especially in those patients with underlying renal impairment.
Paget's Disease: Infuse dose over 4 hours.
Osteolytic bone metastases of breast cancer: Infuse dose over 2 hours. A duration of infusion of more than 2 hours may decrease the risk for renal toxicity, especially in those patients with underlying renal impairment.
Osteolytic bone lesions of multiple myeloma: Infuse dose over 4 hours.

pleural effusion / Delayed / 10.7-10.7
atrial fibrillation / Early / 6.0-6.0
GI bleeding / Delayed / 0-6.0
seizures / Delayed / 2.0-2.0
uveitis / Delayed / 0-1.0
angioedema / Rapid / 0-1.0
anaphylactic shock / Rapid / 0-1.0
heart failure / Delayed / 0-1.0
atrial flutter / Early / 0-1.0
hyperkalemia / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
nephrotic syndrome / Delayed / Incidence not known
visual impairment / Early / Incidence not known
osteonecrosis / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known

anemia / Delayed / 6.0-42.5
constipation / Delayed / 33.2-33.2
dyspnea / Early / 30.4-30.4
hypophosphatemia / Delayed / 1.7-18.0
hypokalemia / Delayed / 4.0-18.0
hypocalcemia / Delayed / 1.0-17.0
hypomagnesemia / Delayed / 4.0-15.0
thrombocytopenia / Delayed / 0-14.0
sinus tachycardia / Rapid / 0-6.0
candidiasis / Delayed / 0-6.0
hypothyroidism / Delayed / 0-6.0
leukopenia / Delayed / 4.0-4.0
psychosis / Early / 0-4.0
neutropenia / Delayed / 0-1.0
stomatitis / Delayed / 0-1.0
iritis / Delayed / 0-1.0
edema / Delayed / 0-1.0
hypotension / Rapid / 0-1.0
bone pain / Delayed / 10.0
hypertension / Early / 6.0
lymphopenia / Delayed / Incidence not known
erythema / Early / Incidence not known
hypernatremia / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
ocular inflammation / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known

musculoskeletal pain / Early / 66.8-66.8
nausea / Early / 0-53.5
fever / Early / 5.0-38.5
fatigue / Early / 12.0-37.2
vomiting / Early / 0-35.7
diarrhea / Early / 0-28.5
anorexia / Delayed / 0-26.0
myalgia / Early / 0-26.0
cough / Delayed / 25.7-25.7
dyspepsia / Early / 0-22.6
abdominal pain / Early / 0-22.6
insomnia / Early / 0-22.2
asthenia / Delayed / 22.2-22.2
injection site reaction / Rapid / 4.0-18.0
sinusitis / Delayed / 15.6-15.6
anxiety / Delayed / 14.3-14.3
arthralgia / Delayed / 13.6-13.6
rhinitis / Early / 0-6.0
syncope / Early / 0-6.0
drowsiness / Early / 0-6.0
back pain / Delayed / 5.0
headache / Early / 10.0
ocular pain / Early / Incidence not known

Aredia

Rx

Intravenous second-generation intravenous bisphosphonate
Used primarily for hypercalcemia of malignancy and to reduce skeletal adverse events in selected cancer patients
For other indications, more potent bisphosphonates are preferred

IF ALBUMIN-CORRECTED SERUM CALCIUM IS 12 to 13.5 mg/dL: 60 mg or 90 mg IV infusion as a single dose; administer over 2 to 24 hours. IF ALBUMIN-CORRECTED SERUM CALCIUM IS MORE THAN 13.5 mg/dL: Give 90 mg IV infusion as a single dose; administer over 2 to 24 hours. RETREATMENT: To allow time for a full response after an initial dose, wait a minimum of 7 days before retreatment. CONCURRENT THERAPY: Vigorous saline hydration is an integral part of hypercalcemia treatment. Urine output should be maintained at approximately 2 L/day. DETERMINING WHICH DOSE TO USE: When treating hypercalcemia of malignancy, the serum calcium should be corrected based upon the serum albumin level to determine the appropriate dose. The following equation may be used: Albumin-corrected serum calcium (mg/dL) = serum calcium (mg/dL) + 0.8(4 - serum albumin [grams/dL]).

Limited data are available. In 1 report of 9 patients (median age 81 years) with moderate to severe hypercalcemia due to primary hyperparathyroidism, a single IV dose of 15 to 60 mg resulted in a therapeutic response in 8 patients with 6 achieving normocalcemia within 1 week. In a case report of a man with primary hyperparathyroidism, a dose of 90 mg IV infusion over 24 hours was effective in reducing his calcium concentration from 13.6 mg/dL to 9.4 mg/dL after 1 week; the patient required a second 60-mg dose approximately 2 months after the first dose and later died of a gastrointestinal hemorrhage. A second case reports the effectiveness of 60 mg IV followed by 60 mg IV 1 month later and 90 mg IV 2 weeks after the second dose in a patient with primary hyperparathyroidism. This patient eventually required surgery to treat the hyperparathyroidism.

Limited data are available. In 1 report, 10 patients with renal failure who developed symptomatic hypercalcemia secondary to use of calcium-based phosphate binders were given pamidronate. Doses ranged between 30 to 60 mg IV with a median dose of 60 mg IV. Serum calcium declined to within normal limits within 3 days in all 10 patients. In a 12-month study of 13 patients on hemodialysis with secondary hyperparathyroidism and mild hypercalcemia, 60 mg IV during hemodialysis every 2 months decreased serum calcium concentrations from a baseline of greater than 12 g/dL to approximately 10 g/dL and significantly decreased iPTH concentrations by 460 pg/mL (p < 0.001). Additionally, calcitriol dosages were increased from a mean dose of 1 mcg/week at baseline to 3 mcg/week after 6 months. Bone mineral density increased by 33% at the lumbar spine and femoral neck after 12 months of therapy (p < 0.01).

A case report describes a dose of 15 mg IV infusion (0.4 mg/kg) given over 2 hours in a boy aged 14 years with end-stage renal disease and secondary hyperparathyroidism; the serum calcium decreased from 12.5 mg/dL to 9.7 mg/dL. Although the serum calcium was controlled for 26 days and allowed for optimization of calcitriol treatment, surgical treatment was eventually required. The patient received acetaminophen prior to the infusion; no adverse reactions were reported.

90 mg IV infusion once a month; administer the dose over 4 hours. Supplement with calcium and vitamin D if intake inadequate and no hypercalcemia is present. Limited data are available in patients with a serum creatinine greater than 3 mg/dL. Withhold treatment if the renal function deteriorates. The optimal duration of therapy is not known; however data from a clinical study in myeloma patients indicate that treatment for 21 months is beneficial.

90 mg IV infusion once every 3 to 4 weeks, administered over 2 hours. Supplement with calcium and vitamin D if intake inadequate and no hypercalcemia is present. Withhold treatment if renal function deteriorates. The optimal duration of therapy is not known; however, data from a clinical study in breast cancer patients indicate that treatment for 24 months is beneficial.

30 mg IV infusion once daily for 3 days (total dose: 90 mg); administer each dose over 4 hours. Supplement with calcium and vitamin D if dietary intake inadequate. A clinician may consider retreatment if clinically indicated. For retreatment, the dose and duration of therapy are the same as for initial treatment. Pamidronate is associated with biochemical remissions lasting 1 to 3 years in most patients. A single dose of zoledronic acid is the drug of choice per treatment guidelines, due to higher potency, the rare need for retreatment within 5 years, and long-term data for reducing pain and lytic lesions and improving quality of life.

1.5 mg/kg/dose (Max: 60 mg/dose) IV every 3 to 4 months.

0.33 to 1 mg/kg/dose IV once daily for 2 to 3 consecutive days every 3 to 6 months. Usual dose range: 6 to 9 mg/kg/year.

0.5 mg/kg/dose IV once daily for 2 consecutive days at baseline, then 0.75 mg/kg/dose IV once daily for 2 consecutive days at week 7, then 1 mg/kg/dose IV once daily for 2 consecutive days at week 15, then 1 mg/kg/dose IV once daily for 2 consecutive days at week 24, then 1.25 mg/kg/dose IV once daily for 2 consecutive days at week 34, then 1.5 mg/kg/dose IV once daily for 2 consecutive days at week 46 (for a cumulative dose of 12 mg/kg/year).

60 mg IV as a single dose.

†Indicates off-label use

No dosage adjustment necessary in patients with mild to moderate hepatic impairment; pamidronate has not been studied in patients with severe hepatic impairment.

No quantitative recommendations are available. Longer infusions (i.e., more than 2 hours), may decrease the risk for renal toxicity, especially in those patients with underlying renal impairment. Obtain a serum creatinine prior to each treatment.
 
CrCl less than 30 mL/minute or Serum creatinine (SCr) greater than 3 mg/dL: Safety and efficacy have not been established in patients with severe renal impairment; there are limited data in patients with CrCl less than 30 mL/minute. If renal function deteriorates (e.g., SCr increase of 0.5 mg/dL in patients with normal baseline SCr or an increase of 1 mg/dL in patients with abnormal baseline SCr) during pamidronate treatment in patients with bone metastases, hold doses of pamidronate until renal function returns to baseline.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Acetaminophen; Aspirin: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Amikacin: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Aminoglycosides: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as pamidronate, as the risk of renal impairment may be increased.
Aspirin, ASA: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Aspirin, ASA; Caffeine: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Aspirin, ASA; Carisoprodol: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity. (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Aspirin, ASA; Omeprazole: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Aspirin, ASA; Oxycodone: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor renal function during concomitant pamidronate and aspirin use due to risk for additive nephrotoxicity.
Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including pamidronate, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Cidofovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as pamidronate, is contraindicated. Pamidronate should be discontinued at least 7 days prior to beginning cidofovir.
Clindamycin: (Moderate) Concomitant use of pamidronate and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Colistimethate, Colistin, Polymyxin E: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including pamidronate, may increase serum concentrations of either drug.
Colistin: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including pamidronate, may increase serum concentrations of either drug.
Cyclosporine: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, including cyclosporine, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Entecavir: (Moderate) Because entecavir is primarily eliminated by the kidneys and pamidronate can affect renal function, concurrent administration with pamidronate may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
Gentamicin: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like pamidronate. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like pamidronate. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and pamidronate due to the risk of glomerulonephritis and nephrotoxicity.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Lanthanum Carbonate: (Moderate) To limit absorption problems, the oral bisphosphonates should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like the oral bisphosphonates, may also be bound by lanthanum carbonate. Separating times of administration will maximize absorption and clinical benefit of the bisphosphonate. Separate the times of administration appropriately. Monitor the patient's clinical status and bone density as recommended to ensure the appropriate response to bisphosphonate therapy is obtained.
Loop diuretics: (Moderate) Because both loop diuretics and intravenously administered bisphosphonates (i.e., alendronate, ibandronate, pamidronate, and zoledronic acid) can cause a decrease in serum calcium, caution is advised when used concomitantly in the treatment of hypercalcemia of malignancy in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Mannitol: (Major) Avoid use of mannitol and pamidronate, if possible. Concomitant administration of nephrotoxic drugs, such as pamidronate, increases the risk of renal failure after administration of mannitol.
Non-Ionic Contrast Media: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor renal function during concomitant pamidronate and nonsteroidal antiinflammatory drug use due to risk for additive nephrotoxicity.
Omeprazole; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Paromomycin: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Plazomicin: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Streptomycin: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Tacrolimus: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as pamidronate may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as pamidronate. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus.
Thalidomide: (Moderate) In patients with multiple myeloma, the risk of renal dysfunction may be higher in patients taking both pamidronate and thalidomide.
Tobramycin: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Vancomycin: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, like vancomycin, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
Voclosporin: (Moderate) Concomitant use of voclosporin and pamidronate may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.

Aredia/Pamidronate Disodium Intravenous Inj Pwd F/Sol: 30mg, 90mg
Pamidronate Disodium Intravenous Inj Sol: 1mL, 3mg, 6mg, 9mg

90 mg/dose IV.

90 mg/dose IV.

Safety and efficacy have not been established; however, 1 mg/kg/day IV for a 2- to 3-day cycle up to a usual dose range of 6 to 9 mg/kg/year IV has been used for osteogenesis imperfecta.

Safety and efficacy have not been established; however, 1 mg/kg/day IV for a 2- to 3-day cycle up to a usual dose range of 6 to 9 mg/kg/year IV has been used for osteogenesis imperfecta.

Safety and efficacy have not been established; however, doses up to 1.5 mg/kg/day IV for a 2-day cycle for a total yearly dose of 12 mg/kg/year IV have been used for osteogenesis imperfecta.

Safety and efficacy have not been established.

The principal pharmacologic action of pamidronate disodium, a first-generation bisphosphonate, is the inhibition of bone resorption. Although the mechanism of antiresorptive action is not completely understood, several factors are thought to contribute to this action. Pamidronate disodium adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. In animal studies, at doses recommended for the treatment of hypercalcemia, pamidronate disodium inhibits bone resorption apparently without inhibiting bone formation and mineralization. Of relevance to the treatment of hypercalcemia of malignancy is the finding that pamidronate disodium inhibits the accelerated bone resorption that results from osteoclast hyperactivity induced by various tumors in animal studies.

Pamidronate is administered by intravenous infusion. Pamidronate distributes extensively to bone and less so to the liver, kidney, or spleen. Bone uptake occurs preferentially in areas of high bone turnover. It is not clear if it crosses the placenta or distributes into breast milk.
 
Pamidronate is not metabolized and is excreted exclusively by the kidney. It has a half-life of 28 +/- 7 hours.  Within 120 hours, 46 +/- 14% of an intravenous dose is excreted unchanged in the urine and 54 +/- 14% is retained in the body. Cumulative urinary excretion is linearly dose-related. Eventually, nearly 100% of the dose is eliminated renally. The terminal phase elimination half-life in bone is estimated to be approximately 300 days.
 
Studies in rats show that pamidronate is rapidly cleared from circulation and taken up by the bones, the liver, the spleen, teeth, and tracheal cartilage. Radioactivity is eliminated from most soft tissues within 1 to 4 days; however it is detectable in the liver for 1 month and the spleen for 3 months. High levels of radioactivity are detectable in the bones, trachea, and teeth for 6 months.

Pamidronate is poorly absorbed and poorly tolerated when administered orally.

After giving radiolabeled pamidronate IV to rats, approximately 50% to 60% is rapidly adsorbed by bone and slowly eliminated by the kidneys. In rats given 10 mg/kg IV, approximately 30% appears in the liver shortly after administration and redistributes to bone or is eliminated by the kidneys over the next 24 to 48 hours.

Pamidronate is classified as FDA pregnancy risk category D. Pamidronate may cause fetal harm when administered to a pregnant woman. No adequate and well-controlled studies have been conducted in pregnant women, although a few reports in the literature do exist. In one report, a single dose of 90 mg pamidronate was administered IV to a pregnant woman during gestation week 28; the infant was born at 29 weeks and required treatment for hypocalcemia. At 1 year of life, the infant was developing normally. The other 2 cases involve women with osteogenesis imperfecta who received pamidronate prior to conception. Both infants were born after 37 weeks gestation, and both acquired osteogenesis imperfecta. One of the infants required treatment for hypocalcemia, and the other had bilateral talipes, which may or may not be secondary to pamidronate administration. At 16 and 14 months of life, respectively, both patients were of normal weight and height. After a bisphosphonate is incorporated into bone matrix it is gradually released from the bone over a period of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into systemic circulation, is directly related to the total dose and duration of bisphosphonate use. Therefore, there is a theoretical risk of fetal harm if a woman becomes pregnant during or after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration on this risk has not been established. Although these 3 reports demonstrate that administration of pamidronate during pregnancy may not be associated with a significant risk to the fetus or embryo, it is still recommended that pamidronate not be administered to pregnant women, if possible. If a patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Furthermore, in those infants that are exposed to pamidronate in utero, serum calcium concentrations should be monitored for the first few days after birth.

According to the manufacturer, it is not known if pamidronate is excreted into breast milk. Based on pharmacokinetics, it is expected that pamidronate will be excreted in human breast milk; however, a woman breast-feeding her infant started receiving 30 mg pamidronate IV once monthly shortly after initiating breast-feeding. Expressed breast milk was discarded for 48 hours after each dose. Pamidronate (lower limit of detection 0.4 mcmol/L) was not detected in the breast milk in pooled samples taken 0—24 hours and 25—48 hours after the first dose. The low bioavailability most likely limits the amount excreted in breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.