Dosing and uses of Aredia (pamidronate)
Adult dosage forms and strengths
powder for reconstitution
- 30mg
pamidronate injection solution as disodium
- 3mg/mL
- 6mg/mL
- 9mg/mL
Hypercalcemia of Malignancy
Moderate hypercalcemia (ie, corrected serum calcium 12-13.5 mg/dL): 60-90 mg single-dose IV infusion over 2-24 hours
Severe hypercalcemia (ie, corrected serum calcium > 13.5 mg/dL): 90 mg single-dose IV infusion over 2-24 hours
Other information
- Longer infusions (ie, >2 hours) may decrease renal toxicity risk, especially with pre-existing renal insufficiency
- May repeat after at least 7 days in patients showing partial or complete response if serum calcium does not remain in normal range
Paget's Disease
30 mg IV infused over 4 hours qDay for 3 consecutive days (ie, total cumulative dose 90 mg)
Limited patients have received >1 treatment in clinical trials; may consider retreatment when clinically indicated
Osteolytic Bone Metastases of Breast Cancer
90 mg IV infusion over 2 hours q3-4Weeks
Osteolytic Bone Lesions of Multiple Myeloma
90 mg IV infusion over 4 hours qMonth
Prevention of Androgen Deprivation-induced Osteoporosis (Off-label)
60 mg IV infusion over 2 hours every 3 months or 90 mg administered once over 3-4 hours
Other Indications & Uses
Hypercalcemia of malignancy
Off-label: spondyloarthropathy
Pediatric dosage forms and strengths
Safety & efficacy not established
Geriatric dosage forms and strengths
Hypercalcemia of malignancy
Moderate hypercalcemia (ie, corrected serum calcium 12-13.5 mg/dL): 60-90 mg single-dose IV infusion over 2-24 hours
Severe hypercalcemia (ie, corrected serum calcium > 13.5 mg/dL): 90 mg single-dose IV infusion over 2-24 hours
Longer infusions (ie, >2 hours) may decrease renal toxicity risk, especially with pre-existing renal insufficiency
May repeat after at least 7 days in patients showing partial or complete response if serum calcium does not remain in normal range
Paget's disease
30 mg IV infused over 4 hours qDay for 3 consecutive days (ie, total cumulative dose 90 mg)Limited patients have received >1 treatment in clinical trials; may consider retreatment when clinically indicated
Osteolytic bone metastases of breast cancer
90 mg IV infusion over 2 hours q3-4Weeks
Osteolytic bone lesions of multiple myeloma
90 mg IV infusion over 4 hours qMonth
Prevention of androgen deprivation-induced osteoporosis (off-label)
60 mg IV infusion over 2 hours every 3 months or 90 mg administered once over 3-4 hours
Aredia (pamidronate) adverse (side) effects
>10%
Anemia (42.5%)
Urinary tract infectious disease (18.5%)
Hypokalemia (18%)
Hypophosphatemia (18%)
Hypocalcemia (12%)
Hypomagnesemia (12%)
1-10%
Seizure (2%)
Frequency not defined
Common
- HTN
- Fever
- Abdominal pain, appetite loss, dyspepsia, nausea, vomiting
- Injection site reaction
- Bone pain
- Cough. dyspnea, URI, sinusitis
Serious
- Osteonecrosis (primarily involving the jaw) reported predominantly in pts w/ cancer
- Focal segmental glomerulosclerosis
Postmarketing Reports
General: reactivation of Herpes simplex and Herpes zoster, influenza-like symptoms
CNS: confusion and visual hallucinations, sometimes in the presence of electrolyte imbalance
Skin: rash, pruritus
Special senses: conjunctivitis, orbital inflammation
Renal and urinary disorders: Renal tubular disorders (RTD); tubulointerstitial nephritis, focal segmental glomerulosclerosis including the collapsing variant, nephrotic syndrome
Laboratory abnormalities: hyperkalemia, hypernatremia, hematuria
Allergy: Rare instances of allergic manifestations have been reported, including hypotension, dyspnea, or angioedema, and, very rarely, anaphylactic shock
Osteonecrosis (primarily involving the jaw) reported predominantly in cancer patients treated with IV bisphosphonates; many of these patients were also receiving chemotherapy and corticosteroids which may be risk factors for ONJ
Respiratory, thoracic and mediastinal disorders: ARDS, interstitial lung disease
Musculoskeletal and connective tissue disorders: Severe and occasionally incapacitating bone, joint, and/or muscle pain; atypical subtrochanteric and diaphyseal femoral fractures
Warnings
Contraindications
Pregnancy
Hypersensitivity
Cautions
Associated with renal toxicity, including potential renal failure (do not exceed single dose of 90 mg)
Severe renal impairment, musculoskeletal pain
Electrolyte abnormalities and myelosuppression may occur
Increased risk of osteonecrosis of the jaw (advise patients against dental work during IV bisphosphonate treatment)
Atypical subtrochanteric and diaphyseal femoral fractures reported with bisphosphonates; may present as thigh/groin pain in absence of trauma
May cause fetal harm when administered to pregnant women; bisphosphonates are incorporated into the bone matrix and gradually released over periods of weeks to years
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if crosses in to breast milk, avoid
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Aredia (pamidronate)
Mechanism of action
Bisphosphonate which inhibits bone resorption via actions on osteoclast activity, leading to an indirect increase in bone density
Pharmacokinetics
Half-Life: 21-35 hours
Duration: hypercalcemia of malignancy (IV): 2 wk to 2 mth
Bioavailability: Poor; pharmacokinetic studies not available
Metabolism: None
Renal clearance: 49 mL/min
Excretion: Urine
Onset
- Hypercalcemia of malignancy: Initial effect 1-2 days; max effect 5-7 days (IV)
- Paget's disease: 1-3 months (maximum effect IV)
Administration
IV Incompatibilities
Calcium-containing diluents such as Lr
IV Preparation
Reconstitute by adding 10 mL of SWI to a viaL
May be further diluted in 250-1000 mL of 1/2NS, NS or D5W
IV Administration
Slowly infuse over 2-24 hours
Longer infusion may reduce risk of nephrotoxicity
Storage
Do not store powder for reconstitution above 30°C (86°F)
