During treatment of hypercalcemia of malignancy, it is recommended to maintain patient's urine output at 2 L/day. The risks of zoledronic acid treatment must be carefully considered in patients with renal disease or renal impairment; indication-specific dosing adjustments are recommended.
Aminobisphosphonate; Hypocalcaemic Agent
Zoledronic Acid is a bisphosphonate and acts primarily on bone. It is an inhibitor of osteoclast-mediated bone resorption. The selective action of bisphosphonates on bone is based on their high affinity for mineralized bone. Intravenously administered Zoledronic Acid rapidly partitions to bone and localizes preferentially at sites of high bone turnover. The main molecular target of Zoledronic Acid in the osteoclast is the enzyme farnesyl pyrophosphate synthase. The relatively long duration of action of Zoledronic Acid is attributable to its high binding affinity to bone mineral.
INTRAVENOUS Hypercalcaemia of malignancy: Adult: 4 mg as a single dose by infusion over at least 15 minutes. Retreatment in patients who relapse or who are refractory to initial treatment: 4 mg as an infusion over at least 15 minutes, after at least 1 wk from initial dose. Bone metastases associated w/ solid tumours;Osteolytic lesions associated wI multiple myeloma: Adult: 4 mg infusion over at least 15 mins every 3-4 wk, in conjunction w/ 500 mg Ca & 400 IU vit D oral supplement. Paget’s disease of bone: Adult: Single 5 mg IV infusion over 15 minutes. in conjunction w/ 1500 mg elemental Ca daily in divided doses & 800 IU vit D daily, esp in the 2 wk following zoledronic acid admin. Osteoporosis in postmenopausal women: Adult: Single 5 mg IV infusion over at least 15 minutes, once a year
Aminoglycosides: May lower serum calcium for prolonged periods.
Loop diuretics: May increase risk of hypocalcemia.
Nephrotoxic drugs: Use with caution.
Drugs primarily excreted by the kidney: Exposure may be increased with renal impairment. Monitor serum creatinine in patients at risk.
Pregnancy; lactation; children. Cardiac disease (avoid fluid overload). Renal impairment. Monitor serum electrolytes, calcium, phosphate & magnesium. Assess renal function before each dose. Withhold treatment if there is worsening of renal function (increase of 44 micromolesll in patients w/ normal baseline creatinine or increase in 88 micromoles/I in those w/ abnormal baseline creatinine); restart treatment at precious dose when creatinine return to w/in 10% of baseline. Ensure adequate hydration throughout therapy & maintain urinary output of 2 L/day. Increased risk of renal impairment wI small infusion vol & rapid infusion. Increased risk of bronchoconstriction in aspirin-sensitive patients. Consider dental exam w/ appropriate corrective action before initiating treatment in patients at risk of osteomyelitis & osteonecrosis of the jaws (e.g. infection, anaemia, pre-existing viral disease, trauma, coagulation disorders). Hard & soft tissue oral assessment to be carried out every 3-4 mth & avoid invasive dental procedures while on treatment.
Electrolyte disturbances (e.g. hypocalcaemia); GI disturbances: dizziness; hypersensitivity reactions; blood disorders e.g. anaemia; wt loss; dyspnoea; iritis; uveitis; conjunctivitis; influenza-like symptoms; myalgia; arthralgia; fever; rigors; renal impairment; taste disturbance; dry mouth; stomatitis; chest pain; cough; CNS effects; pruritus; rash; sweating; asthenia; peripheral oedema; hypertension; bradycardia.
This drug is not recommended in women of childbearing potential. If a patient becomes pregnant while taking or after taking this drug, the patient should be informed of the potential hazard to the fetus. Use is contraindicated. (AU,UK) A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. (US)
Patients who have received doses higher than those recommended should be carefully monitored. Over dosage may cause clinically significant renal impairment, hypocalcemia, hypophosphatemia, and hypomagnesemia. Clinically relevant reductions in serum levels of calcium, phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate, and magnesium sulfate, respectively. Single doses of Zoledronic Acid should not exceed 5 mg and the duration of the intravenous infusion should be no less than 15 minutes.
Store below 30° C prior to opening. Protect from moisture and light. Zoledronic Acid must be kept out of the reach and sight of children.
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