CMS Bisphosphonate Drug Therapy Form

Summary Of Evidence

N/A

Analysis of Evidence

N/A

Note: Etidronate disodium IV has been removed from this policy because it is no longer available in the United States.

Bisphosphonate drugs act to inhibit normal and abnormal bone reabsorption. This action is helpful in reducing pain, reversing hypercalcemia, preventing and reducing fractures in a range of diseases that directly or indirectly impact bone modeling and remodeling.

Bisphosphonates are available in both oral and parenteral forms. Coverage is limited to those drugs administered parenterally (IV). Bisphosphonates are indicated parenterally for osteoporosis and heterotrophic ossification when the patient has failed a trial of the oral drug or has insurmountable issues related to absorption, compliance or dosing posture.

 pamidronate disodium IV, and zoledronic acid IV, are covered for the following indications:

1. Hypercalcemia associated with malignancy
   Osteoclastic hyperactivity resulting in excessive bone resorption is the underlying complication with metastatic bone disease and hypercalcemia associated with malignancy. Most cases of hypercalcemia, associated with malignancy, occurs in patients who have breast cancer, squamous-cell tumors of the lung or head and neck, renal-cell carcinoma, and certain hematologic malignancies (multiple myeloma and some types of lymphomas). Bisphosphonates, in conjunction with hydration, are indicated for moderate or severe hypercalcemia associated with malignancy with or without bone metastases.
2. Cancer Treatment-Induced Bone Loss (CTIBL) in Breast and Prostate Cancer
   Breast Cancer
   Cytotoxic chemotherapy: There are 2 mechanisms of cytotoxic chemotherapy inducing bone loss. First, there is a direct negative effect of the cytotoxic therapy on bone cells, predominantly osteoblasts and, second, many women who are premenopausal have cytotoxic therapy effects on ovarian function, which results in gonadal loss. In addition, in premenopausal women, surgery (oophorectomy) or radiation therapy to the ovary results in bone loss. Hormone therapy, tamoxifen in premenopausal women, and the aromatase inhibitors result in bone loss, as well as gonadotropin-releasing hormone (GnRH) antagonists/agonists, which shut off ovarian function. All of these result in estrogen depletion.
   
   Prostate Cancer
   In prostate cancer, cytotoxic therapy again has a negative effect not only on testicular function but also on bone. Surgical therapy, hormone therapy, including antiandrogens and GnRH agonists/antagonists, results in androgen depletion. The final common pathway, estrogen and androgen depletion, results in a decrease in bone mineral density.
3. Bone metastases secondary to solid tumors, breast cancer, and prostate cancer
4. Multiple Myeloma
5. Osteolytic lesions due to metastases
6. Paget’s Disease of bone (osteitis deformans) *See additional information for zoledronic acid below.
   Intravenous bisphosphonates are indicated for moderate to severe Paget’s disease of bone.
7. Prophylaxis and treatment of heterotopic ossification associated with spinal cord injury, traumatic brain injury, hip replacement, and burns
   It is indicated parenterally when the patient has failed a trial of the oral drug or has insurmountable issues related to absorption, compliance or dosing posture.

Besides the indication listed above, pamidronate sodium is covered for the following indications:

1. Osteogenesis Imperfecta
2. Fibrous dysplasia of bone (McCune-Albright syndrome)

Ibandronate sodium, pamidronate or zoledronic acid are covered for the following indication:

Treatment of osteoporosis when there are no drug classification contraindications. There also needs to exist either one or more of the following:

• • Demonstrated intolerance or contraindication for FDA approved oral bisphosphonates dosing regimens, or insurmountable issues related to absorption, compliance or dosing posture.
  • When adequate trials of FDA-approved oral bisphosphonates result in fallen Bone Mass Density and/or failure to suppress bone turnover (e.g. persisting high bone -turnover marker measurements).

Evidence in the medical record should clearly support the need for the intravenous administration of bisphosphonates for the treatment of osteoporosis.

Ibandronate sodium is covered for:

1. Hypercalcemia associated with malignancy
2. Bone metastases secondary to solid tumors, breast cancer, prostate cancer

 Zoledronic acid - *Injection is covered for the treatment of moderate to severe Paget’s disease of bone in men and women:

• • when there is an elevation in serum alkaline phosphatase two times or higher than the upper limit of the age specific normal reference range
  • there is risk for complications from their disease
  • to induce remission (normalization of serum alkaline phosphatase)

This contractor will cover zoledronic acid once per year for these patients because, after a single treatment, an extended period of remission is observed.

If a patent relapses after one year of remission, re-treatment is considered reasonable and necessary if any of the following conditions occur:

• • an increase in serum alkaline phosphatase
  • a failure to achieve normalization of serum alkaline phosphatase
  • as dictated by medical practice for symptom recurrence