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Hepatic safety of itraconazole
Aditya K Gupta1, Elisabeth Chwetzoff, James Del Rosso
1University of Toronto, Toronto, Canada. agupta@execulink.com
Background:
As the use of the newer oral antifungal agents for the treatment of superficial fungal infections becomes more widespread, the issue of safety surrounding their use is becoming an increasingly important consideration. Itraconazole is effective and well tolerated, with most side effects being minor and reversible. The most common adverse events are gastrointestinal upset, headache, and transient skin reaction. There have also been rare reports of hepatitis.
Objective:
To assess the hepatic safety of pulse and continuous itraconazole in the treatment of onychomycosis.
Methods:
An analysis was performed on all itraconazole clinical trials sponsored by Janssen Research Foundation in the treatment of onychomycosis, where there was an assessment of laboratory safety. A review of the published literature was also undertaken to assess the hepatic safety of itraconazole in common practice.
Results:
The data indicate that itraconazole pulse treatment is safe, with no significant differences in the number of code 4 abnormalities (baseline value is in the normal range and at least two values, or the last testing in the observation period, exceed twice the upper limit of normal) in the liver function parameters studied: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin. The incidence of all the code 4 abnormalities was below 2%. In the literature there are reports of symptomatic hepatitis with itraconazole continuous therapy but no published report of symptomatic hepatotoxicity using the pulse regimen.
Conclusions:
Itraconazole pulse therapy for onychomycosis appears to be safe, especially from the perspective of potential liver damage. In the itraconazole package insert liver function tests are recommended for patients receiving continuous itraconazole for periods of time exceeding 1 month. There is no such monitoring requirement for the pulse regimen unless the patient has a history of underlying hepatic disease, the liver function tests are abnormal at baseline, or at any time that there is the development of signs or symptoms suggestive of liver dysfunction.
Insights
Itraconazole pulse therapy for onychomycosis is safe, showing no significant liver function abnormalities. Continuous itraconazole may require liver monitoring, unlike the pulse regimen.
Area of Science:
- Dermatology
- Hepatology
- Pharmacology
Background:
- Oral antifungal agents are increasingly used for superficial fungal infections.
- Itraconazole is effective but has rare reports of hepatitis.
- Assessing the hepatic safety of itraconazole is crucial.
Purpose of the Study:
- To evaluate the liver safety of both pulse and continuous itraconazole regimens.
- Specifically assess hepatic safety in patients with onychomycosis.
Main Methods:
- Analysis of clinical trials on itraconazole for onychomycosis with safety assessments.
- Review of published literature on itraconazole's hepatic safety in clinical practice.
Main Results:
- Itraconazole pulse treatment showed no significant liver function abnormalities (ALT, AST, alkaline phosphatase, bilirubin).
- Code 4 liver function abnormalities occurred in less than 2% of patients on pulse therapy.
- Symptomatic hepatitis is reported with continuous itraconazole, but not with pulse therapy.
Conclusions:
- Itraconazole pulse therapy for onychomycosis appears safe regarding liver damage.
- Liver function tests are recommended for continuous itraconazole exceeding one month.
- Monitoring for pulse itraconazole is only needed for patients with pre-existing liver issues or symptoms.