Itraconazole liver function, abnormal

The toxicity of LEF is similar to MTX (133,134). The most commonly reported side effects are diarrhea, nausea, alopecia, rash, and headache (135). Anecdotally, alopecia seems more common with LEF than with MTX. However, diarrhea and nausea are more common with MTX. LEF has been successfully used in patients who have discontinued MTX due to GI toxicity (97). Although the rate of liver function abnormalities appears similar to that observed with MTX, the rate of severe liver toxicity is lower with LEF (135). Severe toxicity has been mostly reported when LEF is combined with other hepatotoxic agents such as MTX (136) or itraconazole (137). 

Hepatotoxicity Itraconazole has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-existing liver disease, nor a serious underlying medical condition. If liver function tests are abnormal, discontinue treatment. In patients with raised liver enzymes or an active liver disease or who have experienced liver toxicity with other drugs, do not start treatment unless the expected benefit exceeds the risk of hepatic injury. In such cases, liver enzyme monitoring is necessary. 

In a study using the UK General Practice Research Database to determine rates of drug-induced, rare, serious adverse effects on the liver, kidneys, skin, or blood, occurring within 45 days of completing a prescription or refill in 54 803 users of either fluconazole or itraconazole, three had illnesses for which a fluconazole-induced cause could not be ruled out one with thrombocytopenia, one with neutropenia, and one with an abnormal liver function test just after receiving fluconazole (31). The rates were 2.8/100 000 prescriptions (95% Cl = 0.8, 10) for serious, adverse blood events and 1.4/100 000 prescriptions (95% Cl = 0.25, 8.2) for serious, adverse liver events. These results suggest that fluconazole does not commonly have serious adverse effects on the liver, kidneys, skin, or blood. 

The safety of continuous itraconazole (50-200 mg/day for up to 3 months) in the treatment of onychomycosis and dermatomycosis has been reviewed, using pnblished and unpublished data from clinical trials (15). The overall incidence of adverse events in patients who took continuous itraconazole (21%) differed little from that in patients who took either topical miconazole or oral placebo (18%). The most frequently reported adverse events were gastrointestinal disorders (6.7%), headache (4.2%), and skin disorders (2.7%). No data were given on the incidence of serious adverse events attributed to itraconazole. Among laboratory abnormalities, clinically significant rises in liver function tests occurred in 3.4% of 527 patients treated with itraconazole (2.6% in patients treated with 50-200 mg/day for dermatomycosis versus 6.6% in patients treated with 200 mg/day for 3 months for onychomycosis). 

The safety and efficacy of oral cyclodextrin itraconazole (5 mg/kg/day) as antifungal prophylaxis has been assessed in an open trial in 103 neutropenic children (median age 5 years range 0-15 years) (53). Prophylaxis was started at least 7 days before the onset of neutropenia and continued until neutrophil recovery. Of the 103 patients, only 47 completed the course of prophylaxis 27 withdrew because of poor compliance, 19 because of adverse events, and 10 for other reasons. Serious adverse events (other than death) occurred in 21 patients, including convulsions (n = 7), suspected drug interactions (n = 6), abdominal pain (n — 4), and constipation n — 4). The most common adverse events considered definitely or possibly related to itraconazole were vomiting (n = 12), abnormal liver function (n — 5), and abdominal pain (n = 3). Tolerabihty of the study medication at end-point was rated as good (55%), moderate (11%), poor (17%), or unacceptable (17%). There were no unexpected problems of safety or tolerability. 

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