Ketoconazole Recall Urged by Public Citizen Due to Liver Failure Risks

Amid concerns about the risk of liver toxicity from ketoconazole, the consumer advocacy group Public Citizen is asking the FDA to recall all generic Nizoral antifungal treatments from the market. 

Public Citzen sent a petition (PDF) to the FDA on February 24, calling for a ketoconazole recall, since the risk of liver failure, adrenal insufficiency and other adverse drug interactions outweigh the limited benefits provided in treating fungal infections.

Ketoconazole was first introduced in 1981, under the brand name Nizoral, which is no longer sold. However, there ar still several generic ketoconazole medications on the market.

In 2013, the FDA severely restricted use of Nizoral and issued a drug safety communication that indicated Nizoral should only be used if alternative antifungal therapies are not available or cannot be tolerated by the patient.

The same day the FDA warnings were issued, European regulators called for a Nizoral recall. However, the manufacture of name-brand Nizoral tablets was suspended before the warning was issued.

Later that year, Public Citizen’s “Worst Pills, Best Pills” newsletter gave Nizoral a “Do Not Use” classification.

Ketoconazole, first approved in 1981 for the treatment of fungal infections, was linked to liver toxicity, adrenal gland dysfunctions, and a number of adverse drug interactions. However,

Public Citizen notes that the removal of Nizoral from the market has still left several generic versions, and there has been little effect on the drug’s use.

“In 2012, approximately 5.2 million ketoconazole prescriptions were dispensed, of which 609,000 (12 percent) were for tablet formulations, with nonsystemic fungal infections treated in outpatient clinics representing the most common use,” Public Citizen’s petition notes. “By 2014, 462,000 prescriptions were still dispensed for the drug.”

According to Public Citizen, a team of reviewers at the FDA had called for a Nizoral recall, as did European reviewers, but the FDA chose not to force a recall. The group found that the review team found 42 reports of ketoconazole liver toxicity in adverse drug event reports from 1980 through 2011. Half of those patients died, and 90% were hospitalized. A quarter of the patients required live transplants.

“Liver damage can be severe, leading to liver transplant or death in some patients, including in those without a history of liver disease,” the group states in its petition. “Although other antifungal medications in the same class also can cause liver damage, the risk is considerably higher with ketoconazole.”

Public Citizen noted that there are a number of safer alternatives on the market, rendering generic Nizoral unnecessary. The group warned that if the FDA fails to issue a ketoconazole recall, the drug could be responsible for hundreds of preventable cases of serious liver damage every year.