Zometa Intravenous Infusion

Zoledronic acid injection is a bisphosphonate indicated for the treatment of: Hypercalcemia of malignancy. (1.1) Patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy. (1.2) Limitations of Use : The safety and efficacy of zoledronic acid injection has not been established for use in hyperparathyroidism or non-tumor-related hypercalcemia. …

• Hypercalcemia of malignancy 4 mg as a single-use intravenous infusion over no less than 15 minutes. 4 mg as retreatment after a minimum of 7 days
• Multiple myeloma and bone metastasis from solid tumors. 4 mg as a single-use intravenous infusion over no less than 15 minutes every 3 to 4 weeks for patients with creatinine clearance of greater than 60 mL/min
• Reduce the dose for patients with renal impairment
• Coadminister oral calcium supplements of 500 mg and a multiple vitamin containing 400 international units of vitamin D daily
• Administer through a separate vented infusion line and do not allow to come in contact with any calcium or divalent cation-containing solutions
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
• Hypercalcemia of Malignancy The maximum recommended dose of zoledronic acid injection in hypercalcemia of malignancy (albumin-corrected serum calcium greater than or equal to 12 mg/dL [3.0 mmol/L]) is 4 mg
• The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes
• Patients who receive zoledronic acid injection should have serum creatinine assessed prior to each treatment
• Dose adjustments of zoledronic acid injection are not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine less than 400 µmol/L or less than 4.5 mg/dL). …

Injection: 4 mg/5 mL (0.8 mg/mL) single-dose vial for dilution prior to intravenous infusion (3) Injection: 4 mg/5 mL (0.8 mg/mL) single-dose vial for dilution prior to intravenous infusion.

• Zoledronic acid injection is not indicated for use in children
• The safety and effectiveness of zoledronic acid was studied in a one-year, active-controlled trial of 152 pediatric subjects (74 receiving zoledronic acid)
• The enrolled population was subjects with severe osteogenesis imperfecta, aged 1 to 17 years, 55% male, 84% Caucasian, with a mean lumbar spine bone mineral density (BMD) of 0.431 gm/cm 2 , which is 2.7 standard deviations below the mean for age-matched controls (BMD Z-score of -2.7)
• At one year, increases in BMD were observed in the zoledronic acid treatment group. …

Clinical studies of zoledronic acid injection in hypercalcemia of malignancy included 34 patients who were 65 years of age or older. No significant differences in response rate or adverse reactions were seen in geriatric patients receiving zoledronic acid injection as compared to younger patients. …

• Drugs With Same Active Ingredient or in the Same Drug Class Inform patients not to take Reclast or other bisphosphonates during the course of their zoledronic acid injection therapy [see Warnings and Precautions ]
• Renal Impairment • Instruct patients to tell their doctor if they have kidney problems before being given zoledronic acid injection. • Inform patients of the importance of getting their blood tests (serum creatinine) during the course of their zoledronic acid injection therapy [see Warnings and Precautions ]. …

Hypersensitivity to any component of zoledronic acid injection (4) Hypersensitivity to Zoledronic Acid or Any Components of Zoledronic Acid Injection 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) ].

Aminoglycosides: May have an additive effect to lower serum calcium for prolonged periods. ( 7.1 ) Loop Diuretics: Concomitant use with zoledronic acid injection may increase risk of hypocalcemia. ( 7.2 ) Nephrotoxic Drugs: Use with caution. ( 7.3 ) In vitro studies indicate that the plasma protein binding of zoledronic acid is low, with the unbound fraction ranging from 60% to 77%. In vitro studies also indicate that zoledronic acid does not inhibit microsomal CYP450 enzymes. In vivo studies showed that zoledronic acid is not metabolized, and is excreted into the urine as the intact drug. …

Patients being treated with zoledronic acid injection should not be treated with Reclast ® . ( 5.1 ) Adequately rehydrate patients with hypercalcemia of malignancy prior to administration of zoledronic acid injection and monitor electrolytes during treatment. ( 5.2 ) Renal toxicity may be greater in patients with renal impairment. Do not use doses greater than 4 mg. Treatment in patients with severe renal impairment is not recommended. Monitor serum creatinine before each dose. ( 5.3 ) Osteonecrosis of the jaw (ONJ) has been reported. Preventive dental exams should be performed before starting zoledronic acid injection. Avoid invasive dental procedures. …

The most common adverse events (greater than 25%) were nausea, fatigue, anemia, bone pain, constipation, fever, vomiting, and dyspnea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. …

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, zoledronic acid injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no available data in pregnant women to inform the drug-associated risk. …

Clinical experience with acute overdosage of zoledronic acid injection is limited. Two patients received zoledronic acid injection 32 mg over 5 minutes in clinical trials. Neither patient experienced any clinical or laboratory toxicity. Overdosage may cause clinically significant 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. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.