Drug Profile

Itraconazole (ONMEL, SPORANOX) and terbinafine (LAMISIL) were originally approved to treat serious fungal infections in people with compromised immune systems, such as AIDS patients. Terbinafine was previously available only for topical use, but it is now also available in tablet form. Both drugs are now heavily promoted directly to consumers for the treatment of toenail fungus and fungal infections of the fingernails. Fungal infections of the nails (onychomycosis) are generally resistant to topical treatment.

These drugs treat a condition that is neither urgent nor life-threatening. The editors of The Medical Letter on Drugs and Therapeutics said: “The advisability of taking either of these expensive drugs [itraconazole or terbinafine] for months to treat an infection that is mainly cosmetic and may relapse is unclear.”[2] Our warning to consumers is stronger: Using these drugs for a cosmetic condition is risky.

In fact, Public Citizen’s Health Research Group first designated terbinafine and itraconazole as “Do Not Use” drugs in February 1999 because toenail fungus is a cosmetic condition, and because these drugs have been associated with many cases of liver failure.

The FDA issued a public health advisory in May 2001 about using itraconazole or terbinafine to treat nail fungus because itraconazole has been associated with congestive heart failure and liver toxicity, and terbinafine has been associated with liver toxicity.[3]

Itraconazole (ONMEL, SPORANOX)

The FDA has received reports of multiple cases in which itraconazole-treated patients developed congestive heart failure, including some deaths. The FDA believes that itraconazole contributed to or may have been the cause of the congestive heart failure in some of these cases. The FDA also has examined 24 cases of liver failure possibly associated with the use of itraconazole: these cases also include some deaths.[3]

FDA staff more completely described the cases of congestive heart failure associated with itraconazole in an article in The Lancet. The median age of the patients was 57 years, and the youngest patient was 15 years old. Sixty-five percent of the patients were female, and 50% were receiving itraconazole for fungal nail infection. Of the patients for whom information on the onset of symptoms of congestive heart failure was available, the median onset of symptoms was 10 days after starting the drug and ranged from one to 210 days.[4]

In 2013, a case report was published of a 60-year-old woman who was prescribed itraconazole for onychomycosis (fungal infection of the nail). The data analyzed in the case showed that the patient experienced heart failure associated with her itraconazole therapy.[5]

Terbinafine (LAMISIL)

Terbinafine is mainly used to treat a nonserious, non-life-threatening condition, but it is associated with many serious and life-threatening adverse effects. Moreover, the relapse of toenail fungus with use of terbinafine is reported to be about 15%.[6]

Almost all of the cases of adverse effects with oral terbinafine reported in New Zealand before November 2006 happened within two months of starting treatment with terbinafine.[7]

Patients taking terbinafine for longer than one month should tell their doctor about any symptoms of possible infections. Terbinafine users may need to have certain blood tests performed.[8]

Liver problems. The FDA has reviewed multiple possible terbinafine-associated cases of liver failure; a small number of these cases resulted in death and some others resulted in liver transplants.[3] Oral terbinafine is not recommended for patients with active or chronic liver disease.[7]

Terbinafine's professional product labeling (package insert) carries the following warning about liver failure: “Rare cases of liver failure, some leading to death or liver transplant, have occurred with use of LAMISIL (terbinafine hydrochloride) tablets for the treatment of onychomycosis in individuals with and without pre-existing liver disease.”[9]

Other Toxicities. Other serious adverse effects have been reported with use of terbinafine. These include bone marrow toxicity as well as changes in the lens and retina of the eye.[2],[10]

Swelling. Terbinafine has been associated with severe, hive-like swelling under the skin, especially around the eyes and mouth (angioedema), as well as cutaneous (related to the skin) and systemic lupus erythematosus (a chronic inflammatory connective tissue disease that can affect the joints and many organs).

Blood problems. There also have been reports linking oral terbinafine to blood dyscrasia (an abnormal condition of the blood). This adverse effect has not been reported with the topical cream, gel or solution forms of terbinafine.[10]

In January 2017, the FDA reported that terbinafine can cause blood clots to form in the small blood vessels of the body (thrombotic microangiopathy), which can result in bleeding problems, kidney failure and death.[11]

In June 2013, the FDA issued an advisory that drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome has been reported with oral terbinafine therapy. DRESS syndrome may include cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia (an elevated level of a type of white blood cell called eosinophils), and one or more organ complications, including hepatitis (liver inflammation), pneumonitis (lung inflammation), nephritis (kidney inflammation), myocarditis (heart inflammation) and pericarditis (inflammation of the sac around the heart). The advisory stated that terbinafine therapy should be stopped if symptoms of these disorders occur.[12]

In 2013, Prescrire International published an article noting that cases of taste and smell disorders associated with terbinafine therapy were reported to the Dutch Pharmacovigilance Centre. [13]