From the Guidelines
Itraconazole is the preferred treatment over fluconazole for certain fungal infections, including histoplasmosis, due to its broader spectrum of antifungal activity and higher efficacy against certain resistant species. The most recent and highest quality study, published in 2021 1, supports the use of itraconazole as the first-line treatment for histoplasmosis, with a success rate of 85% compared to fluconazole's 74% success rate 1. Itraconazole has a broader spectrum of antifungal activity, particularly against molds like Aspergillus species, which fluconazole has minimal activity against. It also demonstrates better efficacy against certain resistant Candida species, including Candida krusei and some strains of Candida glabrata.
Key Advantages of Itraconazole
- Broader spectrum of antifungal activity
- Higher efficacy against certain resistant species
- More effective for treating endemic mycoses such as histoplasmosis, blastomycosis, and sporotrichosis
- Achieves higher concentrations in tissues like skin, nails, and lungs
Comparison with Fluconazole
- Fluconazole has a lower success rate for treating histoplasmosis, with a success rate of 74% compared to itraconazole's 85% 1
- Fluconazole is not an acceptable alternative for prophylaxis in immunocompromised subjects due to its inferior activity against H. capsulatum and lower efficacy for treatment of histoplasmosis 1
- Fluconazole may be used as an alternative for patients who cannot take itraconazole, but patients should be followed closely clinically for relapse and antigen concentrations in urine and blood should be monitored quarterly and at the time of suspected relapse 1
Clinical Implications
- Itraconazole should be used as the first-line treatment for histoplasmosis, particularly in immunocompromised patients
- Fluconazole may be used as an alternative, but with close monitoring for relapse and antigen concentrations
- The choice of antifungal agent should be based on the specific fungal infection, patient factors, and potential drug interactions.
From the FDA Drug Label
CLINICAL STUDIES Oropharyngeal Candidiasis Two randomized, controlled studies for the treatment of oropharyngeal candidiasis have been conducted (total n = 344). In one trial, clinical response to either 7 or 14 days of itraconazole oral solution, 200 mg/day, was similar to fluconazole tablets and averaged 84% across all arms In an uncontrolled, open-label study of selected patients clinically unresponsive to fluconazole tablets (n = 74, all patients HIV seropositive), patients were treated with itraconazole oral solution 100 mg b.i.d. Esophageal Candidiasis A double-blind randomized study (n = 119,111 of whom were HIV seropositive) compared itraconazole oral solution (100 mg/day) to fluconazole tablets (100 mg/day).
The advancements of Itraconazole over Fluconazole are:
- Itraconazole can be used to treat patients who are clinically unresponsive to fluconazole.
- Itraconazole has a lower relapse rate compared to fluconazole in some cases. However, it is essential to note that the clinical response rates between itraconazole and fluconazole were similar in the studies mentioned 2.
From the Research
Advancements of Itraconazole over Fluconazole
- Itraconazole has shown to be equivalent or superior to fluconazole in treating osteoarticular infections in rates of cure and recurrence 3.
- In the treatment of nonmeningeal coccidioidomycosis, itraconazole has a trend toward slightly greater efficacy than fluconazole at the doses studied 4.
- Itraconazole is more effective than fluconazole for long-term prophylaxis of invasive fungal infections after allogeneic hematopoietic stem-cell transplantation 5.
- Itraconazole has been shown to be effective in treating nonmeningeal coccidioidomycosis in children, particularly skeletal disease, and infections that are refractory to fluconazole 3.
- More fungal pathogens were found to be resistant to fluconazole than to itraconazole 5.
Comparison of Efficacy
- A study found that 57% of patients responded to fluconazole and 72% responded to itraconazole after 12 months of treatment for nonmeningeal coccidioidomycosis 4.
- Another study found that proven invasive fungal infections occurred in 6 of 71 itraconazole recipients (9%) and in 17 of 67 fluconazole recipients (25%) during the first 180 days after transplantation 5.