d not exceed 4mg and the duration of infusion should be no less than 15minutes [see Warnings And Precautions(5.2)]. In the trials and in postmarketing experience, renal deterioration, progression to renal failure and dialysis, have occurred in patients, including those treated with the approved dose of 4mg infused over 15minutes. There have been instances of this occurring after the initial Zometa dose.
3 DOSAGE FORMS AND STRENGTHS
4 mg/100 mL single-use ready-to-use bottle
4mg/5mL single-use vial of concentrate
4CONTRAINDICATIONS
4.1 Hypersensitivity to ZoledronicAcid or Any Components of Zometa
Hypersensitivity reactions including rare cases of urticaria and angioedema, and very rare cases of anaphylactic reaction/shock have been reported [see Adverse Reactions(6.2)].
5 WARNINGS AND PRECAUTIONS
5.1 Drugs with Same Active Ingredient or in the Same Drug ClassZometa contains the same active ingredient as found in Reclast® (zoledronicacid). Patients being treated with Zometa should not be treated with Reclast or other bisphosphonates.
5.2 Hydration and Electrolyte Monitoring
Patients with hypercalcemia of malignancy must be adequately rehydrated prior to administration of Zometa. Loop diuretics should not be used until the patient is adequately rehydrated and should be used with caution in combination with Zometa in order to avoid hypocalcemia. Zometa should be used with caution with other nephrotoxic drugs.
Standard hypercalcemia-related metabolic parameters, such as serum levels of calcium, phosphate, and magnesium, as well as serum creatinine, should be carefully monitored following initiation of therapy with Zometa. If hypocalcemia, hypophosphatemia, or hypomagnesemia occur, short-term supplemental therapy may be necessary.
5.3 Renal Impairment
Zometa is excreted intact primarily via the kidney, and the risk of adverse reactions, in particular renal adverse reactions, may be greater in patients with impaired renal function. Safety and pharmacokinetic data are limited in patients with severe renal impairment and the risk of renal deterioration is increased [see Adverse Reactions(6.1)]. Preexisting renal insufficiency and multiple cycles of Zometa and other bisphosphonates are risk factors for subsequent renal deterioration with Zometa. Factors predisposing to renal deterioration, such as dehydration or the use of other nephrotoxic drugs, should be identified and managed, if possible.
Zometa treatment in patients with hypercalcemia of malignancy with severe renal impairment should be considered only after eva luating the risks and benefits of treatment. In the clinical studies, patients with serum creatinine greater than 400µmol/L or greater than 4.5mg/dL were excluded.
Zometa treatment is not recommended in patients with bone metastases with severe renal impairment.Inthe clinicalstudies, patients with serum creatinine greater than 265µmol/L or greater than 3.0mg/dL were excluded and there were only 8 of 564 patients treated with Zometa 4mg by 15-minute infusion with a baseline creatinine greater than 2mg/dL. Limited pharmacokinetic data exists in patients with creatinine clearance less than 30mL/min [see Clinical Pharmacology(12.3)].
5.4 Osteonecrosis of the Jaw
Osteonecrosis of the jaw (ONJ) has been reported predominantly in cancer patients treated with intravenous bisphosphonates, including Zometa. Many of these patients we
