FDA PUBLIC HEALTH ADVISORY
THE SAFETY OF SPORANOX® CAPSULES AND
LAMISIL® TABLETS FOR THE TREATMENT OF ONYCHOMYCOSIS
The Food and Drug Administration (FDA) is issuing a public health
advisory concerning Sporanox® (itraconazole) Capsules and Lamisil® (terbinafine
hydrochloride) Tablets for the treatment of onychomycosis. It is important
for physicians to be aware of the association of congestive heart failure
and hepatic adverse events with the administration of these therapies.
Prior to prescribing systemic antifungal drug therapy for the treatment of
onychomycosis, healthcare professionals should consider this new safety
information.
Sporanox® Capsules and Lamisil® Tablets, synthetic antifungal agents,
are approved in the United States for the treatment of onychomycosis [Sporanox®
Capsules, Oral Solution, and Injection are also approved for the treatment
of serious systemic fungal infections (e.g., esophageal candidiasis,
aspergillosis, blastomycosis, and histoplasmosis).]
CARDIAC RISKS
FDA believes that there is a small but real risk of developing
congestive heart failure associated with Sporanox® therapy. Recent
studies conducted in dogs and healthy human volunteers revealed negative
inotropic effects with intravenous (IV) itraconazole. In these studies,
once the drug was stopped the negative inotropic effects resolved. The
mechanism for these cardiac effects has not been determined.
Since becoming aware of these findings, FDA reviewed spontaneous
post-marketing reports received between September 1992 and April 2001 for
congestive heart failure (CHF) in association with itraconazole use.
During this period, FDA received 94 U.S. and international spontaneous
reports of CHF in which itraconazole was listed as a suspect drug. In 58
of the 94 cases, FDA believes itraconazole contributed to or may have been
the cause of CHF. In 26 of the 58 cases, itraconazole was being
administered for the treatment of onychomycosis. Of these 58 cases, 28
were hospitalized. Death was reported in 13 cases. However, the causal
relationship between the 13 deaths and itraconazole is unclear because of
confounding factors, including 10 of the 13 patients who had serious
underlying conditions.
Because of the low but possible risk of cardiac toxicity, Sporanox®
should NOT be administered for the treatment of onychomycosis in
patients with ventricular dysfunction such as CHF or a history of CHF. If
signs or symptoms of CHF occur during treatment for onychomycosis,
Sporanox® should be discontinued.
If signs or symptoms of CHF occur during treatment for more serious
systemic fungal infections, continued Sporanox® use should be reassessed
as to the appropriate risk benefit analysis in relationship to any other
therapeutic options.
HEPATIC RISKS
Both Sporanox® and Lamisil® have been associated with serious hepatic
toxicity, including liver failure and death, including some cases
involving patients who had neither pre-existing liver disease nor a
serious underlying medical condition.
As of April 2001, the FDA is aware of 16 cases of liver failure in
association with Lamisil® Tablet use (including 11 deaths and two liver
transplantations). These patients received Lamisil® Tablets for the
treatment of various dermatologic conditions, including onychomycosis.
FDA's concerns about hepatic risks associated with the use of Lamisil®
do not apply to topically applied formulations of terbinafine, such as
Lamisil® Solution and Lamisil® AT Cream.
As of March 2001, the FDA is aware of 24 cases of liver failure
associated with Sporanox® use (including 11 deaths). These patients
received Sporanox® for the treatment of either onychomycosis or systemic
fungal infections.
Given the possible risks associated with both drugs, FDA wants
healthcare providers to be aware of this new safety information for the
two most commonly prescribed systemic onychomycosis drug therapies.
Because of these risks, the new labeling for both Sporanox® and Lamisil®
recommends that healthcare providers obtain nail specimens for laboratory
testing prior to prescribing the medications for onychomycosis to confirm
the diagnosis. However, there is insufficient data to allow FDA to make
any kind of statement about the comparative safety of Sporanox® and
Lamisil®.
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Last Updated: May 09, 2001
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