March 3, 2008 – The March issue of Drug Safety Update published by the British counterpart of the Saudi Food and Drug Authority (SFDA), the Medicines and Healthcare products Regulatory Agency (MHRA), reported that because of the risk of liver toxicity the approved uses of oral ketoconazole (Nizoral) have been restricted in Great Britain. The British authorities have received reports of serious liver toxicity associated with the use of the drug, including cases resulting in death or that required liver transplantation.

    Oral ketoconazole is now approved only for the following two indications:

· The treatment of dermatophytosis (including athlete’s foot) and Malassezia folliculitis that cannot be treated topically because of the site, extent of the lesion, or deep infection of the skin resistant to, or in patients intolerant to fluconazole (Candeur, Candivast), terbinafine (Lamifen, Lamisil), and itraconazole (Sporanox, Tracon).

· The treatment of chronic mucocutaneous candidosis, cutaneous candidosis, and oropharyngeal candidosis that cannot be treated topically because of the site, extent of the lesion, or deep infection of the skin resistant to, or in patients intolerant to both fluconazole and itraconazole.

    The risk of serious liver toxicity with oral ketoconazole increases with the length of treatment. Treatment for longer than 10 days should be given only after full consideration of the extent of treatment response and of the balance of risks and benefits of continuing treatment.

The signs of liver toxicity include:

· fatigue

· loss of appetite

· yellowing of the skin and/or eyes

· right upper belly pain

· light-colored stools

· dark urine

· itchy skin

ACTIONS THAT HEALTHCARE PROFESSIONALS AND PUBLIC SHOULD FOLLOW:

· Physicians who prescribe oral ketoconazole should inform patients of the signs of liver toxicity listed above.

· Patients who may be taking oral ketoconazole and experience the signs of liver toxicity listed above should immediately seek medical attention.

· Patients and physicians should be aware that oral ketoconazole is not first line treatment for superficial fungal infections.

· Liver function must be monitored before starting treatment with oral ketoconazole, at week 2 and week 4 of treatment, and then monthly.

REPORT ADVERSE DRUG REACTIONS TO THE SAUDI FDA

    The public and health professionals are encouraged to report adverse drug reactions the National Pharmacovigilance Center on the Internet at .