1. Aetna considers calcitriol (Calcijex) or paricalcitol (Zemplar) injection medically necessary for the management of hypocalcemia and/or secondary hyperparathyroidism in members with chronic renal failure undergoing hemodialysis.

2. Aetna considers calcitriol injection experimental and investigational for the treatment of prostate cancer, other cancers, multiple sclerosis, and all other indications because its safety and effectiveness for these indications has not been established.

3. Aetna considers paricalcitol injection experimental and investigational for the treatment of myelodysplastic syndrome and all other indications because its safety and effectiveness for these indications has not been established.

See also CPB 020 - Injectable Medications.

Calcitriol is an anti-hypocalcemic agent or calcium regulator. It is used to suppress the levels of parathyroid hormone (PTH). Calcijex, the parenteral form of calcitriol, is used when patients have not responded to an oral form of calcitriol (Rocaltrol). Calcijex is administered intravenously. Paricalcitol (Zemplar), a vitamin D analog, is administered as an intravenous bolus injection and can be delivered at any time during dialysis. Paricalcitol is the most widely used vitamin D analog in the United States.

Studies have reported that parenteral calcitriol is more effective than pulse oral calcitriol in suppressing PTH (Andress 2001). Available evidence indicates that parenteral vitamin D therapy is associated with fewer episodes of hypercalcemia and hyperphosphatemia and that patients receiving pulse oral calcitriol require more phosphate binders. Because of the documented high non-compliance rate with oral medications in the dialysis population, parenterally administered vitamin D or vitamin D analog is expected to more completely suppress PTH and result in fewer parathyroidectomies.

Calcitriol is also available in oral form. Oral calcitriol (Rocaltrol) is indicated for hypoparathyroidism and pseudohypoparathyroidism. Oral calcitriol is also indicated for secondary hyperparathyroidism and resultant metabolic bone diseases in persons with moderate to severe renal failure not yet on dialysis.

In a review, Beer et al (2005) stated that calcitriol has been reported to exhibit significant anti-neoplastic activity in pre-clinical models of prostate cancer and many other tumor types. Its mechanisms of activity may include inhibition of proliferation, cell cycle arrest, induction of apoptosis, as well as reduction of invasiveness and angiogenesis. Differing mechanisms may be involved in different tumor types and under different experimental conditions. Pre-clinical data suggest that calcitriol acts via a synergistic and/or additive manner when combined with anti-neoplastic agents that are relevant to prostate cancer such as dexamethasone and several classes of cytotoxic agents. However, the anti-neoplastic effects of calcitriol occur at levels that markedly exceed the normal physiological range and cannot be safely attained with conventional daily dosing. Intermittent administration of calcitriol has allowed significant dose escalation. When used with weekly docetaxel (Taxotere), calcitriol produced encouraging results in a single-center phase II clinical trial. These investigators noted that an international placebo-controlled randomized study is under way to ascertain the safety and effectiveness of this combinational therapy.

Niino and colleagues (2008) stated that multiple sclerosis (MS) is a major inflammatory and demyelinating disease of the central nervous system and has an increasing prevalence in populations residing at higher latitudes. This observation may indicate a protective effect of sunlight exposure, which is reduced at higher latitudes and may contribute to insufficient levels of vitamin D in the MS population. The vitamin D hormone is important for bone metabolism and can regulate cell proliferation and differentiation as well as apoptosis and immune regulation in immune cells such as T helper cells and dendritic cells. Evidence from experimental autoimmune encephalomyelitis and prospective studies on MS suggests an important role of vitamin D as a modifiable environmental factor in MS. These provide guidance for future studies with regard to the potential role of vitamin D in the prevention and/or treatment of MS. In this regard, Smolders et al (2008) noted that there is a sound basis on which to initiate double-blind placebo-controlled studies that not only examine the effect of vitamin D on the clinical outcome of MS, but also on the regulatory T cell compartment.

In a clinical trial (n = 12), Koeffler and colleagues (2005) examined the effect of oral paricalcitol in the treatment of patients with myelodysplastic syndrome (MDS) whose disease varied between an international prognostic scoring system of low to high. Drug was well-tolerated in all patients. No responses were observed according to international working group criteria. However, the platelet count of 1 of the 12 subjects rose from 53,500 to 120,000/ul blood over 5 weeks; but the patient succumbed to a fatal fungal infection. These investigators concluded that paricalcitol given as a single agent to MDS patients is therapeutically not very effective; further trials of the vitamin D analog should be considered in combination with other approaches.

Note on documentation requirements: Laboratory tests results (before initiation of therapy) should be documented in the member's medical record showing the medical necessity of the treatment. The member's medical record should clearly document the need for the calcitriol or paricalcitol injection(s). These records should be available upon request.