Company:

Novartis

Bisphosphonate

Zoledronic acid 5mg/100mL bottle; soln for IV infusion.

Treatment of Paget’s disease of bone in men and women.

Paget’s disease of bone is a chronic, focal skeletal disorder characterized by greatly increased and disorderly bone remodeling. Excessive osteoclastic bone resorption is followed by irregular osteoblastic new bone formation, leading to the replacement of normal bone with disorganized, enlarged, and weakened bone structure.

Zoledronic acid is a bisphosphonate that works primarily on bone by inhibiting osteoclast-mediated bone resorption. It rapidly partitions to bone and localizes preferentially at sites of high bone turnover. The relatively long duration of action is attributable to its strong binding affinity to bone mineral.

Treatment with Reclast is indicated in patients with Paget’s disease of bone with elevations in serum alkaline phosphatase (SAP) of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease, to induce remission (normalization of SAP).

After a single treatment with Reclast in Paget’s disease an extended remission period is observed. Retreatment with Reclast may be considered in patients who have relapsed, based on increases in serum alkaline phosphatase, or in those who failed to achieve normalization of their serum alkaline phosphatase, or in those with symptoms, as dictated by medical practice. Patients being treated with Zometa (also from Novartis) should not be treated with Reclast because they contain the same active ingredient.

The efficacy of one infusion of Reclast 5mg versus oral daily doses of risedronate 30mg for 2 months was evaluated in two identical 6-month, randomized, double-blind trials. Therapeutic response was defined as either normalization of SAP or a reduction of ≥75% from baseline in total SAP excess at the end of 6 months. In both trials Reclast demonstrated a superior and more rapid therapeutic response compared with risedronate and returned more patients to normal levels of bone turnover as shown by biochemical markers of formation and resorption.

The 6-month combined data from both trials showed that 96% of Reclast-treated patients achieved therapeutic response compared to 74% of patients treated with risedronate. Also at the 6-month point, 89% of the Reclast-treated patients achieved normalization of SAP levels, compared to 58% of risedronate-treated patients. Most Reclast patients achieved a therapeutic response by the Day 63 visit.

In patients previously treated with oral bisphosphonates, therapeutic response rates were 96% and 55% for Reclast and risedronate, respectively. The comparatively low risedronate response was due to the low response rate (7/23, 30%) in those previously treated with risedronate.

Give by IV infusion over at least 15 minutes. CrCl ≥35mL/min: 5mg. Supplement with calcium 1500mg daily in divided doses and Vit. D 800 IU daily.

Not recommended.

Uncorrected hypocalcemia. Pregnancy (Cat.D). Nursing mothers.

Severe renal impairment: not recommended. Ensure adequate hydration, Vit.D and calcium intake.

Additive hypocalcemic effect with aminoglycosides, loop diuretics. Caution with other nephrotoxic drugs.

Hypocalcemia, headache, dizziness, flu-like syndrome, fatigue, pyrexia, rigors, peripheral edema, asthenia, bone pain, myalgia, GI upset; possible osteonecrosis of the jaw.

Bottle—1

For more information call (800) 693-9993 or visit www.Reclast.com

5/25/07