- Class: Bisphosphonate (Nitrogen-containing bisphosphonate)
- Mechanism of Action:
Zoledronic acid inhibits farnesyl pyrophosphate synthase in the mevalonate pathway within osteoclasts, leading to impaired osteoclast function and apoptosis. This reduces bone resorption and turnover.
Indications
- Oncology uses:
- Prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors (breast cancer, prostate cancer, lung cancer, multiple myeloma).
- Treatment of hypercalcemia of malignancy.
- Used in multiple myeloma for bone disease.
- Non-oncology uses:
- Treatment and prevention of osteoporosis (Reclast brand).
Dosage (Oncology indication)
- For bone metastases:
4 mg IV infusion over at least 15 minutes every 3-4 weeks. - For hypercalcemia of malignancy:
Single dose 4 mg IV infusion; may repeat based on clinical response.
Key Toxicities and Monitoring
- Common adverse effects:
- Acute phase reaction (fever, myalgia, flu-like symptoms)
- Hypocalcemia (monitor calcium and vitamin D)
- Renal toxicity — monitor serum creatinine before each dose
- Osteonecrosis of the jaw (ONJ) — dental exam recommended prior to treatment
- Electrolyte abnormalities (hypophosphatemia, hypomagnesemia)
- Monitoring:
- Renal function prior to each dose; dose adjust or hold if renal impairment worsens.
- Serum calcium and electrolytes regularly.
- Dental evaluation prior to therapy and good oral hygiene.
Drug Interactions
- Caution with nephrotoxic drugs (e.g., NSAIDs, aminoglycosides).
- Avoid concurrent use with other bisphosphonates or denosumab unless clinically indicated.