Zoledronic Acid is indicated in-

• Treatment and prevention of postmenopausal osteoporosis
• Treatment to increase bone mass in men with osteoporosis
• Treatment and prevention of glucocorticoid-induced osteoporosis
• Treatment of Paget's disease of bone in men and women

Limitations of Use: Optimal duration of use has not been determined. For patients at low-risk for fracture, consider drug discontinuation after 3 to 5 years of use.

Zoledronic Acid is a bisphosphonate and acts primarily on bone. It inhibits osteoclast-mediated bone resorption. The selective action of bisphosphonates on bone is due to their high affinity for mineralized bone. Intravenously administered Zoledronic Acid rapidly distributes to bone and accumulates mainly at sites of increased bone turnover. The primary molecular target of Zoledronic Acid in osteoclasts is the enzyme farnesyl pyrophosphate synthase. The long duration of action of Zoledronic Acid is related to its strong binding affinity to bone mineral.

Treatment of Osteoporosis in Postmenopausal Women: The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes.

Prevention of Osteoporosis in Postmenopausal Women: The recommended regimen is a 5 mg infusion given once every 2 years intravenously over no less than 15 minutes.

Osteoporosis in Men: The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes.

Treatment and Prevention of Glucocorticoid-Induced Osteoporosis: The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes.

Treatment of Paget’s Disease of Bone: The recommended dose is a 5 mg infusion. The infusion time must not be less than 15 minutes given over a constant infusion rate.

Re-treatment of Paget’s Disease: Re-treatment with Zoledronic Acid may be considered in patients who have relapsed, based on increases in serum alkaline phosphatase, or in those patients who failed to achieve normalization of their serum alkaline phosphatase, or in those patients with symptoms, as dictated by medical practice.

Calcium and Vitamin D Supplementation: Instruct patients being treated for Paget’s disease of bone on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels, and on the symptoms of hypocalcemia. All patients should take 1500 mg elemental calcium daily in divided doses (750 mg two times a day, or 500 mg three times a day) and 800 international units vitamin D daily, particularly in the 2 weeks following Zoledronic Acid administration.

Instruct patients being treated for osteoporosis to take supplemental calcium and vitamin D if their dietary intake is inadequate. An average of at least 1200 mg calcium and 800-1000 international units vitamin D daily is recommended.

Important Administration Instructions

• Zoledronic Acid injection must be administered as an intravenous infusion over no less than 15 minutes.
• Patients must be appropriately hydrated prior to administration of Zoledronic Acid.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
• Intravenous infusion should be followed by a 10 mL normal saline flush of the intravenous line.
• Administration of acetaminophen following Zoledronic Acid administration may reduce the incidence of acute-phase reaction symptoms.

Method of Administration

• The Zoledronic Acid infusion time must not be less than 15 minutes given over a constant infusion rate.
• The intravenous infusion should be followed by a 10 mL normal saline flush of the intravenous line.
• Zoledronic Acid solution for infusion must not be allowed to come in contact with any calcium or other divalent cation-containing solutions, and should be administered as a single intravenous solution through a separate vented infusion line.
• If refrigerated, allow the refrigerated solution to reach room temperature before administration. After opening, the solution is stable for 24 hours at 2°C to 8°C.

Aminoglycosides: May reduce serum calcium levels for a prolonged period.

Loop diuretics: May increase the risk of hypocalcemia.

Nephrotoxic drugs: Should be used with caution.

Drugs primarily excreted by the kidney: Drug exposure may increase in patients with renal impairment. Serum creatinine should be monitored in patients at risk.

• Hypocalcemia
• Patients with creatinine clearance less than 35 mL/min or with evidence of acute renal impairment
• Hypersensitivity to any component of Zoledronic Acid

The most common adverse reactions (greater than 10%) include pyrexia, myalgia, headache, arthralgia, and pain in extremities. Other important adverse reactions include flu-like illness, nausea, vomiting, diarrhea, and eye inflammation.

Zoledronic Acid may cause fetal harm. Women of childbearing potential should be advised accordingly. This medicine should not be administered to breastfeeding women.

• Hypocalcemia may worsen during treatment. Patients should receive adequate calcium and vitamin D supplementation.
• Renal impairment: A single dose should not exceed 5 mg and infusion duration should be at least 15 minutes. Renal toxicity may increase in patients with pre-existing renal impairment, advanced age, or dehydration. Creatinine clearance should be monitored before each dose.
• Osteonecrosis of the Jaw (ONJ) has been reported. Routine oral examination is recommended before treatment.
• Atypical femur fractures have been reported. Patients experiencing thigh or groin pain should be evaluated for possible femoral fracture.
• Severe bone, joint, or muscle pain may occur. Future doses should be withheld if severe symptoms develop.

Pediatric Use: Not indicated for pediatric patients.

Geriatric Use: Renal function should be monitored carefully.

Renal impairment: Zoledronic Acid is contraindicated in patients with creatinine clearance less than 35 mL/min or with evidence of acute renal impairment. No dosage adjustment is necessary in patients with creatinine clearance greater than or equal to 35 mL/min.

Hepatic impairment: Zoledronic Acid is not metabolized in the liver. No clinical data are available in patients with hepatic impairment.

Patients receiving higher than recommended doses should be monitored carefully. Overdose may result in clinically significant renal impairment, hypocalcemia, hypophosphatemia, and hypomagnesemia. Reductions in serum calcium, phosphorus, and magnesium levels should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate, and magnesium sulfate, respectively. Single doses should not exceed 5 mg and infusion duration should be at least 15 minutes.

Bisphosphonate preparations

Store below 30° C before opening. Protect from light and moisture. Keep out of the reach and sight of children.