Drugs Xagena
Because of a risk of serious hepatotoxicity with Nizoral ( Ketoconazole ), and the availability of other effective antifungal treatments, the Summary of Product Characteristics ( SmPC ) has been revised:
The therapeutic indications have been restricted to patients resistant to, or intolerant of, other effective antifungal therapies
Duration of treatment has been highlighted as a main factor in the risk of serious hepatotoxicity
Several other drugs have been added to the list of contraindications
The special warnings and precautions about hepatotoxicity and monitoring of hepatic function before and during Nizoral use have been amended
New postmarketing adverse drug reactions have been added to the list of undesirable effects.
Further information
Therapeutic Indications
Nizoral tablets are no longer indicated for: prophylactic treatment to prevent mycotic infection in patients with reduced immune responses, e.g. in cancer, during treatment with immunosuppressive medication, or with burns; systemic candidosis; culturally determined dermatophyte infections of fingernails; oesophageal candidosis; chronic, recurrent vaginal candidosis; systemic fungal infections; treatment of Paracoccidioidomycosis, Histoplasmosis, Coccidioidomycosis and Blastomycosis.
The updated indications for Nizoral tablets are:
Treatment of dermatophytosis and Malassezia ( previously called Pityrosporum ) folliculitis that cannot be treated topically because of the site, extent of the lesion or deep infection of the skin, in patients resistant to, or intolerant of, Fluconazole, Terbinafine and Itraconazole.
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, in patients resistant to or intolerant of both Fluconazole and Itraconazole.
Posology and method of administration
The updated information on dosage information and duration of treatment is as follows:
Method of administration: oral. Nizoral should be taken during meals for maximal absorption;
Dosage: adults: one tablet ( 200 mg ) once daily with a meal. If no adequate response is obtained with this dose, the dose should be increased to 2 tablets ( 400 mg ) once daily; children: children weighing from 15 to 30 kg: half a tablet ( 100 mg ) once daily with a meal, children weighing more than 30 kg: same as for adults.
Duration of treatment: for all indications, treatment should be continued without interruption until clinical parameters or laboratory tests indicate that the fungal infection has resolved. An inadequate treatment period may lead to recurrence of the active infection. However, the risk of serious hepatic toxicity increases with longer duration of treatment; courses of greater than 10 days should only be given after full consideration of the extent of treatment response and the risk benefit of continuing treatment, and liver function should be closely monitored. For the treatment of Malassezia infections, treatment should not normally exceed 4 weeks.
Contraindications
In addition to the existing drug interactions and contraindications, several other drugs have been added to the list of contraindicated drugs, including: Disopyramide, Sertindole, Nisoldipine, Eplerenone, ergot alkaloids such as Dihydroergotamine, Ergometrine ( Ergonovine ), Ergotamine and Methylergometrine ( Methylergonovine ).
Special warnings and precautions for use
The updated information on hepatic toxicity and monitoring of hepatic function is as follows: because of the risk for serious hepatic toxicity, Nizoral Tablets should be used only when the potential benefits are considered to outweigh the potential risks, taking into consideration the availability of other effective antifungal therapy.
Hepatic toxicity
Very rare cases of serious hepatic toxicity, including cases with a fatal outcome or requiring liver transplantation, have occurred with the use of oral Ketoconazole. Some patients had no obvious risk factors for liver disease. Cases have been reported that occurred within the first month of treatment, including some within the first week.
The risk of serious hepatic toxicity increases with longer duration of treatment; courses of greater than 10 days should only be given after full consideration of the extent of treatment response and the risk benefit of continuing treatment.
All patients should be counselled at the start of treatment with basic knowledge of the signs and symptoms suggestive of liver toxicity. The patient should be informed to discontinue treatment if they feel unwell or in the event of symptoms such as anorexia, nausea, vomiting, fatigue, jaundice, abdominal pain or dark urine. If these occur, treatment should be stopped immediately and liver function testing should be conducted.
Liver function must be monitored in all patients receiving treatment with Nizoral tablets. Monitor liver function prior to treatment to rule out acute or chronic liver disease. Liver function must be monitored at weeks 2 and 4 of treatment, then continued monthly, with discontinuation of treatment if any liver parameters are elevated above 3 times the normal limit.
In patients with raised liver enzymes, or those who have experienced liver toxicity with other drugs, treatment should only be started in exceptional cases, where the expected benefit exceeds the risk of hepatic injury, and consideration should be given to monitoring liver function tests ( LFTs ) more frequently.
Undesirable effects
The following Postmarketing adverse drug reactions ADRs have been added: anaphylactoid and anaphylactic reactions; angioneurotic oedema; adrenocortical insufficiency; cirrhosis, the reporting rate being very rare.
Source: Medicines and Healthcare product Regulatory Agency MHRA, 2008
XagenaMedicine_2008
