Zoledronic acid (Zometa®)(J3487) is indicated for the following indications:

1. The treatment of hypercalcemia of malignancy (275.42).
2. The treatment of multiple myeloma (203.00-203.02).
3. The treatment of bone metastases from solid tumors in conjunction with standard anti-neoplastic therapy, including bone metastases from multiple myeloma, breast carcinoma, prostate carcinoma, and other solid tumors (162.0-162.9, 170.0-170.9, 174.0-174.9, 175.0-175.9, 185, 189.0-189.9, 193, 195.0, 197.0, 198.0, 198.5, 198.81, 198.82).

NOTE:

Prostate cancer should have progressed after treatment with at least one hormonal therapy.

Date Last Reviewed: 07/2009

Zoledronic acid (Reclast®)(J3488) is indicated for the following indications:

1. The treatment of Paget's disease of bone (731.0) in men and women.

   Treatment is indicated in patients with Paget's disease of bone with elevations in serum alkaline phosphatase 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.
   
   After a single treatment with Reclast in Paget's disease an extended remission period is observed.  Specific re-treatment data are not available. However, re-treatment with Reclast 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.

2. The treatment of osteoporosis to increase bone mass (733.00, 733.01, 733.02, 733.03, 733.09, 733.14) in patients who have documented failure of oral bisphosphonate therapy.
   
   Osteoporosis may be confirmed by the presence or history of osteoporotic fracture or by a finding of low bone mass (BMD more than 2.5 standard deviations below the normal adult reference population [i.e., T-score]).
   
   
3. The treatment of prevention of osteoporosis in postmenopausal women (733.90) who have documented failure of oral bisphosphonate therapy. The recommended regimen is given intravenously once every 2 years.
   
   
4. The treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who are expected to remain on glucocorticoids for at least 12 months (V58.65). Documented failure of oral bisphosphonate therapy is required.

   A 6-12 month trial of oral bisphosphonates will be considered adequate to determine a treatment failure. Failure will be defined as:

   • a new fracture despite bisphosphonate therapy of six months or more, or
   • a T-score ≤ -3.0 despite bisphosphonate therapy of 12 months or more.

   Individual consideration may be given in documented cases for patients who have difficulty with oral bisphosphonate dosing requirements, which include an inability to sit upright for 30 to 60 minutes and/or swallow a pill. Individual consideration may also be given in patients who have esophagitis, gastritis, or esophageal or gastric ulcers prohibiting the use of oral bisphosphonates.

Reclast® (zoledronic acid) injection contains the same active ingredient found in Zometa®, used for oncology indications, and a patient already being treated with Zometa® should not be treated with Reclast®.

Safety and effectiveness in pediatric patients has not been established.

Date Last Reviewed: 07/2009

If the patient can tolerate oral bisphosphonates then the injectable form is considered not medically necessary, and therefore, not covered. A participating, preferred or network provider cannot bill the member for the denied service unless the provider has given advance written notice, informing the member that the service may be deemed not medically necessary and providing an estimate of the cost. The member must agree in writing to assume financial responsibility, in advance of receiving the service. The signed agreement should be maintained in the provider's records.

The use of zoledronic acid for any other diagnosis not listed on this policy is considered experimental/investigational, and therefore, not covered. A participating, preferred, or network provider can bill the member for the denied service.

Coverage for zoledronic acid is determined according to individual or group customer benefits. Zoledronic acid is not reimbursable under the prescription drug benefit.

Description

Zoledronic acid inhibits bone resorption. The antiresorptive mechanism is not fully understood and several factors are thought to contribute to this action. In vitro, zoledronic acid inhibits osteoclastic activity and induces osteoclast apoptosis. Osteoclastic resorption of mineralized bone and cartilage through its binding to bone is blocked by zoledronic acid. Increased osteoclastic activity and skeletal calcium release induced by various stimulatory factors released by tumors are inhibited by zoledronic acid.

See Medical Policy Bulletin X-24 for guidelines on Bone Mineral Density Studies.

NOTE:

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Under the Federal Employee Program, all services that utilize FDA-approved drugs, devices, or biological products are eligible when intended for the treatment of a serious life-threatening condition and when medically necessary and appropriate for the patient’s condition.

Reclast® (Zoledronic Acid) package insert; Novartis Pharmaceutical Corporation, East Hanover, NJ, 04/2007

Zometa® (Zoledronic Acid) package insert; Novartis Pharmaceutical Corporation, East Hanover, NJ, 04/2005

Zoledronic Acid, USPDI, Vol. I, Edition 26, 2006 Micromedex, Inc.

Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis, The New England Journal of Medicine, Vol. 356, No. 18, 05/2007

The Research on Adverse Drug Events and Reports (RADAR) Project, Journal of the American Medical Association, Vol. 293, No. 17, 05/2005

A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density, BONE, Vol. 40, No. 5, 05/2007

Reclast® (zoledronic acid) [package insert]. Novartis Pharmaceutical Corporation; 6/2008.

Reclast® (zoledronic acid) [package insert]. Novartis Pharmaceutical Corporation; 12/2008.

Compston J. Treatments for osteoporosis-looking beyond the HORIZON.  N Engl J Med. 2007;356:1878-1880.

Lyles KW, Colon-Emeric CS, Magaziner JS. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799-1809.

FDA approves osteoporosis drug for men. Endocrine Today-Clinical News on Diabetes and Endocrine Disorders. December 31, 2008.

Yearly zoledronic acid in postmenopausal osteoporosis. N Engl J Med. 2007;357:711-715.

Tosteson ANA, Melton LJ, Dawson-Hughes B, et al. Cost-effective osteoporosis treatment thresholds: the United States perspective. Special Position Paper. National Osteoporosis Foundation. December 2007.

Osteoporosis drugs. JAMA. 2008;300:2846.

National osteoporosis foundation releases new clinical recommendations for low bone mass and osteoporosis incorporating absolute fracture risk. National Osteoporosis Foundation, February 21, 2008.

Zometa®  [package insert]. East Hanover. NJ: Novartis Pharmaceuticals Corporation; March 2008.

Bachmann GA. The utilization of intravenous bisphosphonates. The Female Patient. November 2008.

Kuehn BM. Long-term risks of bisphosphonates probed. JAMA. 2009;301:710-11.

Gnant M, Mlineritsch B, Schippinger W, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009;360:679-691.

Endocrine therapy plus zoledronic acid in premenopausal breast cancer. Correspondence. N Engl J Med. 2009;360:2367-2370.

Reclast® [package insert]. East Hanover. NJ: Novartis Pharmaceuticals Corporation; March 2009. 

Reclast® [package insert]. East Hanover. NJ: Novartis Pharmaceuticals Corporation; May 2009.