Itraconazole Oral Solution for the Treatment of Esophageal Candidiasis
ABSTRACT & COMMENTARY
Synopsis: Itraconazole oral solution had similar efficacy to fluconazole tablets in the treatment of esophageal candidiasis.
Source: Wilcox CM, et al. A randomized, double-blind comparison of itraconazole oral solution and fluconazole tablets in the treatment of esophageal candidiasis. J Infect Dis 1997;176:227-232.
Wilcox and colleagues randomized patients at 15 centers with endoscopically and microbiologically confirmed esophageal candidiasis to receive, on the first day, either two 200 mg capsules of fluconazole with 200 mL water or 20 mL of itraconazole solution (swish and swallow) containing a total of 400 mg. The dose of each on subsequent days was reduced to 200 mg. Appropriate placebos were administered.
Of the 110 assessable patients, 102 had AIDS. The two treatment groups were similar at baseline. The mean duration of treatment was 26.8 days in the itraconazole group and 27.3 days in the fluconazole group; the respective clinical response rates were 94% and 91%. Endoscopic cure was seen in 90% of itraconazole and 80% of fluconazole recipients (95% CI, -0.044-0.232). Clinical relapse rates by 30 days were 18% and 27%, respectively, in the itraconazole and fluconazole treatment groups.
Microbiologic efficacy was observed in 92% of those given itraconazole and 78% of those given fluconazole (95% CI, -0.002 to 0.271). All baseline isolates had an MIC less than 1 mcg/mL to itraconazole (when examined after 24 hours of incubation), while eight isolates from five patients had an MIC greater than 8 mcg/mL to fluconazole. None of these five patients, four of whom were assigned fluconazole, had a mycologic response.
Treatment was discontinued because of drug-related adverse events in one patient receiving itraconazole and two receiving fluconazole.
COMMENT BY STAN DERESINSKI, MD, FACP
A major problem with the use of itraconazole capsules has been erratic and often inadequate absorption. Formulating this triazole as an oral solution in hydroxypropyl-b-cyclodextrin results in 30% greater absorption in normal volunteers. Furthermore, absorption is not dependent upon the presence of gastric acid, as is the case with capsules. Another drawback to the use of itraconazole is its potential for pharmacokinetic drug interactions, a drawback not solved by reformulation.
This study demonstrates that fluconazole encapsulated tablets and itraconazole oral solution are, for all practical purposes, equivalent in the treatment of esophageal candidiasis. There was, however, a trend toward a better mycological response in patients who received itraconazole.
Unfortunately, it is not clear to me that these results can be extrapolated to the treatment of invasive Candida infections. It is not possible to determine in this study whether the excellent mycological response in patients receiving itraconazole was the result of high serum concentrations (which are not reported), high local surface concentrations, or a combination of both. I look forward to additional well-done clinical trials that answer this question.