May 14, 2001
Issues Health Advisory Regarding the Safety of Sporanox® Products and Lamisil® Tablets
to Treat Fungal Nail Infections
Washington, DC (SafetyAlerts) - The Food and Drug
Administration (FDA) has issued a Public Health Advisory to announce significant
safety-related updates to the labeling of Sporanox® (itraconazole) products and Lamisil®
(terbinafine hydrochloride) tablets. Sporanox® and Lamisil® are used to treat nail
(onychomycosis), skin and other systemic fungal infections. The following may be used to
The purpose of today's FDA Public Health Advisory is to alert healthcare professionals to
serious risks associated with the use of Sporanox® and Lamisil®.
FDA believes there is a small but real risk of developing congestive heart failure (CHF)
associated with the use of Sporanox®. Both Sporanox® and Lamisil® have been associated
with serious liver problems resulting in liver failure and death. However, there is
insufficient data to allow FDA to make any kind of statement about the comparative safety
of Sporanox® and Lamisil®.
Results of recent studies of Sporanox® revealed a potential for the drug to weaken the
force of the heart muscle's contractions. This so-called "negative inotropic
effect" was observed when intravenous Sporanox® was injected into anesthetized dogs
and healthy human volunteers. In these studies, the adverse effect on the heart muscle
resolved once the drug was stopped.
Since becoming aware of the study findings, FDA analyzed US and international
post-marketing adverse event reports involving Sporanox that were received between its
approval in September 1992 and April 2001.
During this period, FDA received 94 cases in which patients receiving Sporanox® developed
CHF. In 58 of the 94 cases, FDA believes Sporanox® contributed to or may have been the
cause of CHF. In 26 of these 58 cases, Sporanox® was being administered to treat fungal
nail infections. Of these 58 patients, 28 were hospitalized. Death was reported in 13
cases. However, the causal relationship between the 13 deaths and Sporanox® is very
unclear because of confounding factors. For example, 10 of the 13 patients who died had
serious underlying conditions.
In response to the study findings and the analysis of the post-marketing adverse event
reports, FDA has added additional information to the current "black box" warning
in the Sporanox® labeling. The warning now states that Sporanox® should not be
administered for the treatment of fungal nail infections in patients with evidence of
cardiac dysfunction, such as CHF, or a history of CHF. The Sporanox® "black
box" warning also includes important information about heart-related adverse events
caused by drug interactions.
If signs and symptoms of CHF occur during treatment of fungal nail infections, the revised
labeling recommends that Sporanox® should be discontinued. If signs and symptoms of CHF
occur during treatment for more serious fungal infections involving other parts of the
body, the revised labeling recommends that continued use of Sporanox® should be
reassessed by the physician.
The advisory also alerts healthcare professionalsto rare cases of serious liver problems
including liver failure, transplantation and death associated with the useof Sporanox®
products and Lamisil® tablets. While adverse liver effects were already included in the
labeling for both products, FDA decided to include this information in the advisory
because some cases involved patients who had neither pre-existing liver disease nor a
serious underlying medical condition.
FDA's concerns do not apply to the topically applied versions of Lamisil® such as cream
As of April 2001, FDA has received and reviewed 16 possible Lamisil®-associated cases of
liver failure, including 11 deaths and two liver transplantations.
As of March 2001, FDA has received and reviewed 24 cases of liver failure possibly
associated with Sporanox®, including 11 deaths. Approximately half of the liver failure
cases received Sporanox® for fungal nail infections or other dermatological infections.
Given the possible serious risks associated with Sporanox® products and Lamisil®
tablets, the new labeling for both products now recommends that healthcare professionals
should obtain nail specimens for laboratory testing prior to prescribing the medications
for fungal nail infections, to confirm the diagnosis.
In conjunction with FDA's advisory, the manufacturer of Sporanox® (Janssen Pharmaceutica
Products, L.P. of Titusville, NJ and Ortho Biotech Products, L.P. of Raritan, NJ) and
Lamisil® (Novartis Pharmaceuticals of East Hanover, NJ) are notifying healthcare
professionals of the labeling changes by issuing "Dear Healthcare Professional"
FDA encourages healthcare professionals and patients to report adverse events associated
with the use of Sporanox® and Lamisil® to FDA's MEDWATCH Program. Reports may be
submitted to MEDWATCH by phone at 1-800-FDA-1088, by fax at 1-800-FDA-1078, by mail at
MEDWATCH, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MEDWATCH web
site at www.fda.gov/medwatch.
The full text of the FDA Public Health Advisory is available at FDA's MedWatch web site here.