Systemic Therapy Program
Search Again

Date



Disease Group



Cancer Type

Document Type

Drug Monographs
Treatment Regimens
Scientific Name:
PAMIDRONATE
Brand Name(s):
Aredia®

Drug Monograph

Pharmacology

Mechanism of Action

Pamidronate binds to hydroxyapatite and inhibits osteoclastic bone resorption; unlike etidronate, pamidronate is not associated with inhibition of bone mineralization.

Pharmacokinetics

Oral Absorption:
very low  (1%)- diminishes when given with food or calcium
Distribution:
45-53% adsorbed to bone, mostly in areas of high turnover; stomach, liver, spleen, tracheal cartilage, macrophages; excretion in breast-milk unknown
cross blood brain barrier? No information
Vd, PPB: No information
Metabolism:
No metabolism
Excretion:
renal; non-renal clearance is a result of uptake by bone, with subsequent slow elimination via bone turnover;
Urine: yes; I.V.: 30% unchanged within 12 hours
t½ a  0.6 hours t½ b in bone, 300 days
Cl:  1.1mL/min

Side Effects

Most adverse reactions reported for Pamidronate during concurrent chemotherapy are the same for patients receiving placebo instead of Pamidronate.
IMMEDIATE ONSET
   flu-like symptoms (transient fever-36%, arthralgias- 12%, malaise, headache)
   infusion site reaction (10-20%)- transient redness, swelling and pain
   laboratory abnormalities- hypocalcemia, hypokalemia, hypomagnesemia, hypophosphatemia
EARLY ONSET
  (days to weeks)
   skeletal pain (50-65%)
   anemia, leukopenia
   anorexia, constipation, gastrointestinal hemorrhage, nausea
   atrial fibrillation, hypertension, syncope, tachycardia
   hypothyroidism
DELAYED ONSET  (weeks to months)
   renal failure (rare)
   osteonecrosis of the jaw (ONJ)-  (rare)

Therapeutics

Approved Indications

• Malignancy-related hypercalcemia
• Multiple myeloma
• Osteolytic bone metastases

Routes

Intravenous infusion over 2 to 4 hours, or longer
Intravenous injection
Longer infusion time if renal failure

Administration

• Mix in 250-500mL solution (5% Dextrose, Normal Saline) and infuse over 2 to 4  hours (longer infusion time if Creatinine >180mmol/L or renal impairment)
• May infuse using ambulatory infusion device over 2-5 hours
Hypercalcemia indication
• 30-60mg Dose: Mix in 250-500mL solution (5% Dextrose, Normal Saline) and infuse over 2 hours (longer infusion time if Creatinine >180mmol/L or renal impairment)
• 90mg Dose: Mix in 500-1000mL solution (5% Dextrose, Normal Saline) and infuse over 4 to 6 hours

IV Compatibility

Sodium chloride 0.45% or 0.9%
Dextrose 5%

Dosing

Intravenous:
Multiple myeloma
4-6 weeks:
• 90 mg IV for one dose on day 1

Osteolytic bone metastases
3-4 weeks:
• 90 mg IV for one dose on day 1

Malignancy-related hypercalcemia
• 90 mg (30-90 mg) IV for one dose

Pediatric:
Intravenous:
• 1-2 mg/kg IV over 3-24 h has been used for malignancy-related hypercalcemia

Contraindications

• Cardiac failure (avoid overhydration, use smaller infusion volume) • Renal function impairment

Monitoring

Clinical Monitoring

The risk of adverse reactions may be greater in patients with impaired renal function
RECOMMENDED CRITERIA
• Preventative dental examination PRIOR to start of Pamidronate treatment
• Baseline and regular renal function tests [serum creatinine, BUN]
• Serum electrolytes, including calcium, phosphate, and magnesium
 HYPOCALCEMIA
0. Serum Calcium >2.10 mmol/L
1. Serum Calcium =2.10 to 1.93 mmol/L
2. Serum Calcium =1.92 to 1.74 mmol/L
3. Serum Calcium =1.73 to 1.51 mmol/L
4. Serum Calcium <1.50 mmol/L
Rated on assessment of anti-hypercalcemia response and at periodic visits or in response to patient complaint
SUGGESTED CRITERIA
Complete blood count including differential, platelets and hemoglobin (CBC) before each cycle of treatment, especially if fever
 HYPERCALCEMIA- Response Criteria
0. Serum Calcium <2.64 mmol/L
1. Serum Calcium =2.64 to 2.88 mmol/L
2. Serum Calcium =2.89 to 3.12 mmol/L
3. Serum Calcium =3.13 to 3.37 mmol/L
4. Serum Calcium >3.37 mmol/L
Rated on assessment of anti-hypercalcemia response and at periodic visits or in response to patient complaint

Extravasation Hazard

Local thrombophlebitis at infusion site.

Significant Interactions

Calcium-containing compounds, magnesium-, iron- or aluminum-containing compounds, vitamin D & analogs, calcitonin, foscarnet, food- milk products.

Product Information

Commercial Product Description

Vials with 30mg, 60mg, 90mg for reconstitution.

Pharmaceutical Considerations

Injection:
30 mg and 90 mg vials; as anhydrous pamidronate disodium; preservative-free.8 Store at room temperature.
Reconstitute each 30 mg and 90 mg vial with 10 mL of SWI to yield pamidronate concentrations of 3 mg/mL and 9 mg/mL, respectively. Reconstituted solution is stable for 24 hours at room temperature.

Diluted solution for infusion:
Must be further diluted with NS or D5W to concentrations less than or equal to 0.36 mg/mL. Diluted solution is stable for 24 hours at room temperature.

Compatibility:
Pamidronate should not be mixed with calcium-containing IV solutions such as Ringer’s solution.

Handling Risk Level

Pregnancy CPOSSIBLE HAZARDOUS DRUG
FDA Pregnancy Risk Factor C

  • Consider handling this drug using precuations outlined in CCNS Policies for Occupational Safety, Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy

Note

HANDLING RISK LEVEL:

HAZARD RISK LEVEL 3
FDA Pregnancy Risk Factor C
• Consider handling this drug using precautions outlined in CCNS Policies for Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy
• Go to "Additional Information" tab (above) for links to CCNS Policies

Availability & Funding

Administrative Information (Nova Scotia)

• CCNS Provincial Formulary Status- Basic Level • Go to "Additional Information" tab (above) for links to Provincial Formulary of Cancer Drugs • Pharmacare Formulary Status- Non-Formulary