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Alert for Healthcare
Professionals
Tacrolimus (marketed as Protopic)
6/2006: The issues described in this alert have
been addressed in product labeling.
FDA Alert [3/2005]:
The FDA has issued a public health advisory to
inform healthcare professionals and patients about a potential
cancer risk from use of Protopic (tacrolimus). This concern is based
on information from animal studies, case reports in a small number
of patients, and knowledge of how drugs in this class work. It may
take human studies of ten years or longer to determine if use of
Protopic is linked to cancer. In the meantime, this risk is
uncertain, and FDA advises Protopic should be used only as labeled,
for patients after other prescription treatments have failed to work
or cannot be tolerated.
This information reflects FDA’s preliminary
analysis of data concerning this drug. FDA is considering, but has
not reached a final conclusion about, this information. FDA intends
to update this sheet when additional information or analyses become
available.
To report any unexpected adverse or serious
events associated with the use of Protopic, please contact the FDA
MedWatch program at 1-800-FDA-1088 or
http://www.fda.gov/medwatch/report/hcp.htm
Recommendations
Physicians with patients using Protopic, or who are considering
prescribing the drug, should consider the following:
-
Use Protopic only as a second-line agent for
short-term and intermittent treatment of atopic dermatitis,
a form of eczema,
in patients unresponsive to, or intolerant of other treatments.
-
Avoid use Protopic in children younger than 2 years
of age. The effect of Protopic on the developing immune system in
infants and children is not known.
-
Use Protopic only for short periods of time, not
continuously. The long term safety of Protopic is unknown.
-
Children and adults with a weakened or compromised
immune system should not use Protopic.
-
Use the minimum amount of Protopic needed to control
the patient’s symptoms. In animals, increasing the dose resulted in
higher rates of cancer.
Data Summary
Although tacrolimus is not genotoxic and does not interact directly
with DNA, it may have a potential to impair local immunosurveillance.
Carcinogenicity studies conducted with topical application of
tacrolimus in mice demonstrated a dose-dependent development of
lymphoma. The systemic administration of tacrolimus in kidney and
liver transplant patients has been associated with increased
susceptibility to infection and development of lymphoma and skin
malignancies.
As of December 2004, the FDA had received 19 cases of postmarketing
reports linking Protopic with cancer-related adverse events. Three
cases occurred in children up to 16 years of age, and 16 cases
occurred in adults. Two deaths in adults were reported related to
complications of the cancers, and 8 hospitalizations were reported,
including 2 in pediatric patients.
The 19 postmarketing cases included 9 lymphomas, 10 cutaneous
tumors, of which 7 occurred at the site of Protopic application, as
well as cases of squamous cell carcinoma, cutaneous sarcoma,
malignant melanoma and other tumor types. The median time until
diagnosis after initiation of treatment with Protopic was 150 days,
with a range between 21 days and 790 days. Six cases also reported
lymphadenopathy. Two cases reported pre-existing serious conditions,
and 4 cases reported a recurrence or aggravation of a pre-existing
malignancy. Three additional cases were confounded by other possible
risk factors, including environmental exposure, or pre-existing
conditions that may have been pre-malignant.
The systemic form of tacrolimus (Prograf) is known to cause both
skin cancers and lymphoma in humans by suppressing the body’s normal
immune defenses against cancer. The cancer risk increases with
higher doses and longer treatment courses of Prograf. Protopic is
sometimes absorbed through the skin, though usually at very low
amounts. Occasionally, children who have been treated with Protopic
have had measurable blood levels of the drug, in the range of
patients treated with Prograf. The potential for systemic
immunosuppression is unknown and the role of Protopic in the
development of the cancer-related events in the individual
postmarketing cases is also uncertain.
FDA Patient Information Sheet
http://www.fda.gov/cder/drug/InfoSheets/patient/ProtopicPIS.pdf
Report serious adverse events to FDA's MedWatch at
1-800-FDA-1088; or
http://www.fda.gov/medwatch/report/hcp.htm
Questions? Call Drug Information, 1-888-INFO-FDA
(automated) or 301-827-4570
druginfo@fda.hhs.gov
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Date created: February 14, 2005, updated, June 15, 2006 |
