Common Brand Names: Zometa, Reclast
Therapeutic Class: Bone-resorption inhibitor, 3rd generation bisphosphonate
Common Injectable Dosage Forms:
Zometa Injection (solution): 4 mg/5 mL
Reclast Injection (solution): 5 mg/100 mL
For the treatment of hypercalcemia of malignancy* (Zometa): The maximum recommended dose is 4 mg infused over at least 15 minutes. A minimum of 7 days should elapse before retreatment. Mild, asymptomatic hypercalcemia may be treated with vigorous saline hydration therapy alone. Patients should be adequately rehydrated prior to administration.
For the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy (Zometa): The recommended dose is 4 mg infused over at least 15 minutes every 3-4 weeks.
*Albumin-corrected serum calcium ≥12 mg/dL [3.0 mmol/L]) [Ca + (0.8 x (4.0 - patient’s measured albumin in mg/dL))].
Treatment of active Paget’s disease (Reclast): 5 mg as a single dose over no less than 15 minutes.
Treatment of osteoporosis in postmenopausal women and for osteoporosis prophylaxis: 5 mg IV once yearly over no less than 15 minutes.
Secondary fracture prophylaxis or after surgical repair of hip fracture (Reclast): 5 mg once yearly given over no less than 15 minutes.
Administration and Stability:
Zometa concentrate must be diluted with 100 mL of 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP. Calcium-containing infusion solutions, such as Lactated Ringer’s solution, must not be used. Diluted solutions should be used immediately or refrigerated at 2°C-8°C (36°F-46°F) and brought back to room temperature prior to infusion. Zometa should be administered as a single intravenous solution in a line separate from all other drugs. The dose must be given over no less than 15 minutes to minimize renal deterioration. Reclast is provided ready-to-infuse solution, no further dilution required, and must use vented line. Patients should be adequately hydrated, and serum Cr should be assessed prior to each treatment with zoledronic acid. Patients must be on calcium with vitamin D supplement to avoid hypocalcemia.
Pharmacology/Pharmacokinetics:
Zoledronic acid is a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. In vitro, zoledronic acid inhibits osteoclastic activity and induces osteoclast apoptosis. It also blocks the osteoclastic reabsorption of mineralized bone and cartilage through its binding to bone. Certain malignancies and metastatic bone diseases cause hypercalcemia by stimulating osteoclastic hyperactivity either through tumor invasion of bone or through other factors such as parathyroid-hormone-related protein. Excessive bone reabsorption spills calcium into the blood causing polyuria and GI distress and resulting in dehydration and a decrease in the glomerular filtration rate. Because hypoalbuminemia sometimes accompanies the hypercalcemia, an adjustment of serum calcium is used to determine the severity of the condition (See Dosage Ranges).
Drug and Lab Interactions:
Aminoglycosides, loop diuretics, and other nephrotoxic drugs (see Contraindications/Precautions).
Contraindications/Precautions:
Contraindicated in patients hypersensitive to zoledronic acid or any other bisphosphonates. Zoledronic acid is not recommended if serum Cr is >4.5 mg/dL. Use with extreme caution in patients with severe renal impairment due to the risk of renal deterioration. Patients receiving zoledronic acid should have serum creatinine assessed prior to each treatment. Patients should be well hydrated prior to treatment and loop diuretics should not be used until the patient is adequately rehydrated. Use with caution with other nephrotoxic drugs. Other bisphosphonates have caused bronchospasm in patients with aspirin-sensitive asthma. Bisphosphonates have been associated with osteonecrosis, primarily of the jaw. Do not use in pregnancy and use appropriate contraceptives during and after treatments. Pregnancy Category D.
Monitoring Parameters:
CBC, calcium, BUN/Cr, electrolytes, magnesium, phosphate
Adverse Effects:
Adverse effects to Zometa are usually mild and transient. The most common adverse effects are (in order of incidence) fever, chills, bone pain, dyspnea, nausea, constipation, anemia, diarrhea, vomiting, insomnia, anxiety, confusion, coughing, hypotension, and urinary tract infection. May also cause hypophosphatemia, hypokalemia, and hypomagnesemia.
Common Clinical Applications:
Useful for treatment hypercalcemia from malignancy and metastatic bone disease.
