DESCRIPTION
Zoledronic acid is a bisphosphonate which inhibits osteoclast-mediated bone resorption. Although the antiresorptive mechanism is not completely understood, several factors are thought to contribute to this action. Bisphosphonates show selective action on bone due to their high affinity for mineralized bone. Zoledronic acid is drawn to bone in areas of high bone turnover where its main target is the osteoclast. It binds to mineralized bone targeting the osteoclast. Within the osteoclast it inhibits the action of the enzyme farnesyl pyrophosphate synthase, resulting in disruption of the osteoclast cytoskeleton and cell death. This action prevents the increased osteoclastic activity and accompanying skeletal calcium release of certain tumors and other conditions
Examples of zoledronic acid include Zometa®, an intravenous infusion which can be given more than once a year if required and Reclast®, an annual single-dose intravenous infusion.
REFER TO DECISION SUPPORT TREE
POLICY
Zoledronic acid for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Bone metastases
Hypercalcemia
Multiple myeloma
Osteopenia (i.e., bone mineral density [BMD] T-score between -1 and -2.5)
Osteoporosis (i.e., BMD T-score -2.5 or lower)
Paget’s disease (osteitis deformans)
Zoledronic acid for the prevention of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Osteopenia (i.e., bone mineral density [BMD] T-score between -1 and -2.5)
Osteoporosis (i.e., BMD T-score -2.5 or lower)
Zoledronic acid for the treatment / prevention of other conditions/diseases, including, but not limited to, the following is considered investigational: (See Applicable Tennessee State Mandate Requirements below.)
Hypercalcemia associated with hyperparathyroidism or other non-tumor-related conditions
Rheumatoid arthritis
Kidney or liver transplant
Hypogonadal young women following an allogeneic stem cell transplant
MEDICAL APPROPRIATENESS
Zoledronic acid for the treatment of the following is considered medically appropriate if ALL of the following criteria are met:
Bone metastases if ALL of the following:
Requested agent is Zometa®
Disease is from solid tumor malignancy (e.g., breast cancer, prostate cancer, non-small cell lung cancer [NSCLC], neuroendocrine tumors, thyroid carcinoma)
Individual has adequate renal function (e.g., creatinine clearance greater than 30 mL/min)
Treatment is ALL of the following:
In conjunction with standard antineoplastic therapy
Following at least one hormonal therapy with disease progression for prostate cancer diagnosis
Hypercalcemia if ALL of the following:
Requested agent is Zometa®
Condition is due to malignancy
Calcium lab value is albumin-corrected calcium (cCa) of >12 mg/dL [3.0 mmol/L] using the formula: cCa in mg/dL=Ca in mg/dL + 0.8 ( 4.0 g/dL - patient albumin (g/dL)
Multiple myeloma (including solitary plasmacytoma and smoldering multiple myeloma) if ALL of the following:
Requested agent is Zometa®
Treatment is for osteolytic lesions
Treatment is in conjunction with standard antineoplastic therapy
Osteopenia (i.e., bone mineral density [BMD] T-score between -1 and -2.5) with ALL the following:
Diagnosis of prostate cancer
Condition is secondary to androgen-deprivation therapy
Osteoporosis (i.e., BMD T-score -2.5 or lower) if ALL of the following:
Requested agent is Reclast®
Condition is ANY ONE of the following:
Diagnosed in a male (to increase bone mass)
Glucocorticoid-induced
Postmenopausal
Paget’s disease of bone (osteitis deformans) if ALL of the following:
Requested agent is Reclast®
Condition is moderate to severe that is ANY ONE of the following:
Presenting with serum alkaline phosphatase elevation of greater than or equal to the upper limit of the age-specific normal reference range
Symptomatic
In individual at risk for complications from their disease
Zoledronic acid for the prevention of ANY ONE of the following is considered medically appropriate if the following criteria are met:
Osteopenia (i.e., bone mineral density [BMD] T-score between -1 and -2.5) if ALL of the following:
Diagnosis of non-metastatic prostate cancer
Individual is beginning / continuing long-term androgen deprivation therapy
Osteoporosis (i.e., BMD T-score -2.5 or lower) if ALL of the following:
Requested agent is Reclast®
Individual is ANY ONE of the following:
Initiating / continuing systemic glucocorticoid therapy if ALL of the following:
Daily dosage equivalent to 7.5 mg or greater of prednisone
Expected to remain on glucocorticoids for at least 12 months
Postmenopausal
Diagnosed with non-metastatic prostate cancer
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
The American Hospital Formulary Service Drug Information recognizes the use of zoledronic acid (i.e., Zometa®) for the prevention of: aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women receiving adjuvant hormonal therapy for early-stage breast cancer.
One open-label randomized phase III, four-arm clinical trial recognizes the use of zoledronic acid (i.e., Zometa®) for the prevention of: aromatase inhibitor-associated bone loss (AIBL) in premenopausal women receiving adjuvant hormonal therapy for early-stage breast cancer.
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
No controlled studies were found in the published literature that validate the use of zoledronic acid in the treatment/prevention of any other conditions/diseases.
SOURCES
Gnant M., Mlineritsch B., Stoeger, H., Luschin-Ebengreuth G., Heck, D., H., Menzel, C., et al. (2011). Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomized trial. The Lancet Oncology, 12 (7), 631-641.
Hillner, B.E., Ingle, J.N., Chelebowski, R.T., Yee, G.C., Janjan, N.A., Cauley, J.A., et al. (2011). American Society of Clinical Oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. Journal of Clinical Oncology, 29 (9), 1221-1227.
Lexi-Comp Online. (2011, May). AHFS DI. Zoledronic acid. Retrieved June 30, 2011 from Lexi-Comp Online with AHFS.
MedicineNet, Inc. (2011). Medterms.com. Definition of osteopenia. Retrieved September 30, 2011 from http://www.medterms.com/script/main/art.asp?articlekey=8048.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2011, June). Zoledronic acid. Retrieved June 30, 2011 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2011). NCCN Drugs & Biologics Compendium™. Zoledronic acid. Retrieved June 30, 2011 from the National Comprehensive Cancer Network.
U. S. Food and Drug Administration. (2011, February). Center for Drug Evaluation and Research. Label and Approval History. Zometa® (zoledronic acid). Retrieved June 30, 2011 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021386s004lbl.pdf.
U. S. Food and Drug Administration. (2011, March). Center for Drug Evaluation and Research. Label and Approval History. Reclast® (zoledronic acid) injection. Retrieved June 30, 2011 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021817s006lbl.pdf.
ORIGINAL EFFECTIVE DATE: 6/9/2007
MOST RECENT REVIEW DATE: 10/11/2011
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
Pharmaceutical Decision Support Tree
Zoledronic Acid (Zometa®, Reclast®)
Is the requested medication being used to treat hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions, rheumatoid arthritis, kidney or liver transplant, or hypogonadal young women following an allogeneic stem cell transplant?
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #2
Is the agent being requested zoledronic acid (i.e., Zometa®)?
If yes, to question #3
If no, go to question #4
The agent being requested is Zometa® for ANY ONE of the following?
Hypercalcemia of malignancy
For prevention or treatment of osteoporosis to androgen-deprivation therapy with non metastatic prostate cancer
Multiple myeloma including solitary plasmacytoma and smoldering multiple myeloma when used in conjunction with standard antineoplastic therapy for bone disease including osteopenia
Bone metastases with ANY ONE of the following:
Metastasis from solid tumors (e.g., breast cancer, lung cancer, neuroendocrine tumors, prostate cancer, thyroid cancer) when used in conjunction with standard antineoplastic therapy
Metastasis associated with prostate cancer that has progressed after treatment with at least one hormonal therapy
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
The agent being requested is Reclast® for ANY ONE of the following?
Osteoporosis for ANY ONE of the following:
For the prevention and treatment of postmenopausal woman
For the treatment of a male with osteoporosis
Paget’s disease of the bone for the treatment of ANY ONE of the following:
The men or women have elevations of serum alkaline phosphatase two times or higher than the upper limit of the age-specific normal reference range
The individual is symptomatic or at risk for complications from their disease
Treatment and prevention of glucocorticoid-induced osteoporosis with ALL of the following:
The individual is either initiating or continuing systemic glucocorticoids
The daily dosage is equivalent to 7.5 mg or greater of prednisone
The individual is expected to remain on glucocorticoids for at least 12 months
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.