Description

Prior to administration, the required amount of concentrate from one vial must be further diluted with 100 ml of calcium-free infusion solution (0.9% w/v sodium chloride solution or 5% w/v glucose solution). The duration of infusion must not be less than 15 minutes. After addition of the solution to the infusion media, the infusion solution should be used as soon as possible. If storage of the infusion solution is necessary, hold at 2-8º C for not more than 24 hours. If refrigerated, the solution must be allowed to reach room temperature before administration. Zoledronic Acid must not be mixed with calcium or other divalent cation-containing infusion solutions, such as Lactated Ringer's solution, and should be administered as a single intravenous solution in a line separate from all other drugs.

In clinical studies, Zoledronic acid has been administered concomitantly with commonly used anticancer agents, diuretics, antibiotics and analgesics without interactions. Caution is advised when Zoledronic acid are administered with aminoglycosides, since these agents may have an additive effect to lower serum calcium level for prolonged periods. In multiple myeloma patients, the risk of renal dysfunction may be increased when Zoledronic acid is used in combination with thalidomide. Concomitant use of loop diuretics with Zoledronic acid increases the risk of hypocalcemia. Caution is indicated when Zoledronic acid is used with other potentially nephrotoxic drugs.

The drug is contraindicated if patients have hypersensitivity to the active substance or to any of the excipients or to any bisphosphonates; severe renal impairment (Creatinine clearance <30 ml/min); pregnancy and lactation.

The post-dose side-effects are headache, nausea, anorexia, fatigue, osteonecrosis of jaw, anemia, bone pain, constipation, fever, vomiting, flu-like syndrome, hypocalcemia, myalgia, arthralgia and hypophosphataemia.

Zoledronic acid is contraindicated during pregnancy and in breast-feeding women. It is also not recommended for use in children and adolescents below 18 years of age.

Patients must be appropriately hydrated prior to administration of Zoledronic Acid. This is especially important in the elderly and for patients receiving diuretic therapy. Adequate hydration can be achieved by the patient drinking two glasses of fluid (such as water) before and after the infusion. Serum levels of calcium, phosphate, magnesium and potassium, as well as serum creatinine should be carefully monitored after initiating Zoledronic Acid therapy. If hypocalcemia, hypophosphatemia or hypomagnesemia occurs, short-term supplemental therapy may be necessary. Moreover, careful renal function monitoring should be considered.

Patients with renal impairment: The use of Zoledronic Acid is not recommended in patients with severe renal impairment (Creatinine clearance <30 ml/min). No dose adjustment is necessary in patients with creatinine clearance >60 ml/min. Based on creatinine clearance the following dose should be used in patient with impaired renal function: CrCl > 60 ml/min: 4 mg (5 ml) CrCl 50-60 ml/min: 3.5 mg (4.4 ml) CrCl 40-49 ml/min: 3.3 mg (4.1 ml) CrCl 30-39 ml/min: 3 mg (3.8 ml)