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DUR: Use of Topical Calcineurin Inhibitors in the Medi-Cal Fee-For-Service (FFS) Population

Drug Use Review: Educational Information

On March 10, 2005 the Food and Drug Administration (FDA) issued a Public Health Advisory for the topical calcineurin inhibitors Pimecrolimus Cream (Elidel ®) and Tacrolimus Ointment (Protopic ®).1

On January 19, 2006, the FDA approved updates to the product labels and a Patient Medication Guide to be given to patients receiving pimecrolimus cream and tacrolimus ointment.2

Pimecrolimus cream and tacrolimus ointment are topical immunosuppressant calcineurin inhibitors that are applied to the skin, and are the only approved drugs in this class.

The FDA’s concerns are based on information from animal studies, case reports in small numbers of patients and on the mechanism of action of the drugs.1

  • Although a causal relationship has not been established, there have been rare cases of malignancy reported in patients being treated with topical calcineurin inhibitors
  • Phase I animal data suggest that the risk of cancer increases with increased exposure to topical pimecrolimus or tacrolimus
  • Long-term safety data of these drugs has not been established

The FDA and the manufacturers recommend that healthcare providers, patients and caregivers consider the following.1, 3, 4

  • Use as second-line treatment in patients unresponsive to, or intolerant of, other
    treatments (e.g. topical corticosteroids)
  • Indicated for short-term and intermittent treatment of mild to moderate atopic
    dermatitis (eczema)
  • Avoid the use of pimecrolimus and tacrolimus in children younger than 2 years of
    age. The effect of these agents on the developing immune system in infants and
    children is not known
  • Do not use in patients with a weakened or compromised immune system
  • Use the minimum amount of pimecrolimus and tacrolimus needed to control the patient’s symptoms

Topical pimecrolimus and tacrolimus are NOT indicated in children less than 2 years old and high-dose tacrolimus (0.1%) is NOT indicated in children less than 16 years of age.4

For more information on label changes or to obtain Patient Medication Guides, visit the FDA News page.

Medi-Cal conducted a retrospective study of beneficiaries with paid pharmacy claims for calcineurin inhibitors. Patients with at least one pharmacy paid claim for a calcineurin inhibitor between
July 1, 2005 and December 31, 2005 were included in the analysis. The claims for these beneficiaries were analyzed for an 18-month lead-in period of January 1, 2004 through June 30, 2005 to determine if prescribing patterns were appropriate, including the trial/failure of another agent prior to initiation of treatment with a calcineurin inhibitor. It should be noted that only oral prednisone, oral methylprednisolone and topical corticosteroids were considered to determine previous therapies.
Medi-Cal also recognizes that other agents (i.e. prednisolone, oral dexamethasone, Vitamin D analogs, etc.) can be used to treat eczema that were not included in this analysis.

There were a total of 714 continuously eligible beneficiaries identified who received a calcineurin inhibitor agent during the study period (July 1, 2005 through December 31, 2005).

  • 22 percent of patients began treatment with a topical calcineurin inhibitor drug before trial/failure of a topical corticosteroid, oral prednisone, or oral methylprednisolone
  • 15 percent of all patients with paid claims for topical calcineurin inhibitors were infants less than 2 years old
  • 36 percent of all patients ages 2 through 15 with a paid claim for tacrolimus ointment were treated with the high dose (0.1 percent) strength

Medi-Cal is monitoring the utilization of all topical calcineurin inhibitors for appropriate use.

To report any unexpected adverse events associated with these agents, contact the FDA Medwatch program at 1-800-FDA-1088; by fax at 1-800-FDA-0178; by mail to MedWatch; Food and Drug Administration; HFD-410; 5600 Fishers Lane; Rockville, MD 20857-9787.

  1. FDA Public Health Advisory Elidel (pimecrolimus) Cream and Protopic (tacrolimus) Ointment. Food and Drug Administration, March 10, 2005. http://www.fda.gov/cder/drug/advisory/elidel_protopic.htm.
  2. FDA News FDA Approves Updated Labeling with Boxed Warning and Medication Guide for Two Eczema Drugs, Elidel and Protopic. Food and Drug Administration, January 19, 2006. https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
  3. ELIDEL (Pimecrolimus, Novartis) Package Insert. http://www.pharma.us.novartis.com/product/pi/pdf/elidel.pdf
  4. PROTOPIC (Tacrolimus, Astellas Pharma Inc.) Package Insert. http://www.astellas.us/docs/protopic.pdf


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