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.

Zoledronic acid (Zometa) may be considered medically necessary for ANY of the following:

• The treatment of hypercalcemia of malignancy. Defined as an albumin-corrected calcium (cCa) of greater than or equal to 12 mg/dL (3.0 mmol/L) using formula: cCa in mg/dL=Ca in mg/dL + 0.8(4.0g/dl – patient albumin [g/dL]). It is recommended that a minimum of seven (7) days elapse before retreatment, to allow for full response to initial dose; or
• The treatment of multiple myeloma in combination with primary myeloma therapy. Recommended frequency is every three (3) to four (4) weeks; or
• 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, thyroid carcinoma, non-small cell lung cancer, kidney cancer, and other solid tumors. Recommended frequency is every three (3) to four (4) weeks; or
• In breast cancer for individuals receiving adjuvant therapy along with calcium and vitamin D supplementation to maintain or improve bone mineral density and reduce risk of fractures; or
• Prevention or treatment of osteoporosis during androgen deprivation therapy (ADT) for individuals with high fracture risk; or
• Prevention of skeletal-related events in men with castration-resistant prostate cancer who have documented bone metastases and creatinine clearance greater than 30 mL/min.

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

The use of zoledronic acid (Zometa) is considered experimental/investigational, and therefore, non-covered. There is lack of peer reviewed literature to support its use for any other indication not listed above.

Zoledronic acid (Reclast) may be considered medically necessary for ANY of the following:

• The treatment of Paget's disease of bone in men and women.
  • Treatment is indicated in individuals 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 individuals who have relapsed, based on increases in serum alkaline phosphatase, or in those individuals who failed to achieve normalization of their serum alkaline phosphatase, or in those individuals with symptoms, as dictated by medical practice. or
• The treatment of osteoporosis to increase bone mass in individuals diagnosed with osteoporosis who have documented failure of oral bisphosphonate therapy. Recommended regimen is once every year; or
• Prevention of osteoporosis in postmenopausal women who have documented failure of oral bisphosphonate therapy. Recommended regimen is once every two (2) years; or
• Treatment and prevention of glucocorticoid-induced osteoporosis 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. Documented failure of oral bisphosphonate therapy is required.

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]).  Osteoporosis may also be diagnosed in individuals with osteopenia (BMD T-score between 1 - 2.5 standard deviations below normal adult reference population) AND Fracture Risk Assessment Tool (FRAX) indicates ten (10) year probability for major osteoporaotic fracture of greater than or equal to 20% or the ten (10) year probability of hip fracture is greater than or equal to 3%. 

• Failure of oral bisphosphonate therapy will be defined as a six (6) to twelve (12) month trial with Any of the following: 
  • A new fracture despite bisphosphonate therapy of six months or more; or
  • A T-score less than or equal to -3.0 despite bisphosphonate therapy of 12 months or more.
• Individual consideration may be given:
  • In documented cases for individuals 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 individuals who have esophagitis, gastritis, achalasia, stricture, dysmotility, gastric bypass procedures, celiac disease, crohn’s disease, infiltrative disorders or esophageal or gastric ulcers prohibiting the use of oral bisphosphonates. 

Contraindications

• Reclast injection contains the same active ingredient found in Zometa, used for oncology indications, and an individual already being treated with Zometa should not be treated with Reclast.
• Hypocalcemia.
• Individuals with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment.

The use of zoledronic acid (Reclast) is considered experimental/investigational, and therefore, non-covered. There is lack of peer reviewed literature to support its use for any indications not listed above.

Pediatric

The use of zoledronic acid for pediatric population is considered experimental/investigational, and therefore, non-covered.  Safety and effectiveness in pediatric population has not been established.

If the individual can tolerate oral bisphosphonates then the injectable form is considered not medically necessary, and therefore, not covered.

Refer to medical policy X-24 for guidelines on Bone Mineral Density Studies.

"Experimental/Investigational (E/I) service are not covered regardless of place of service".

The administration of Zoledronic Acid (Reclast, Zometa) is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

• Link to Provider Resource Center for the Medical Policy Update

06/2018, Coverage Guidelines Revised for Zoledronic Acid (Reclast, Zometa)

• Link to Diagnosis Codes

• Link to References