Drug‐Drug Interaction between Itraconazole and the Antiretroviral Drug Lopinavir/Ritonavir in an HIV‐1–Infected Patient with Disseminated Histoplasmosis

Abstract

We describe a drug-drug interaction between coformulated lopinavir/ritonavir and itraconazole in a patient infected with human immunodeficiency virus type 1 who had disseminated histoplasmosis. Coadministration of these agents led to a strong increase in itraconazole concentrations and a decrease in concentrations of its metabolite, hydroxyitraconazole, which is equally active pharmacologically. The dosage of itraconazole was reduced when it was used in combination with lopinavir/ritonavir.

In vitro activity of isavuconazole against 140 reference fungal strains and 165 clinically isolated yeasts from Japan

“…However, the drug has serious safety concerns associated with renal toxicity, hypokalaemia and hypomagnesaemia [5] and recent case reports document clinical failure with this agent against infections caused by non-albicans Candida such as Candida rugosa [6], Candida lusitaniae [7] and Candida glabrata [8]. Azoles are potent compounds; however, some of the drugs on the market have problems such as a narrow spectrum and resistance issues with fluconazole (FLC), as well as specific issues such as the variability of bioavailability of posaconazole [9] and the drug-drug interactions of itraconazole (ITC) [10]. The echinocandins have emerged as useful therapeutic options for invasive candidiasis, however case reports describing reduced in vitro activity and clinical failure of caspofungin against C. albicans, C. glabrata and Candida krusei have appeared [11][12][13][14].…”

Coccidioidomycosis in Persons Infected with HIV Type 1

“…For example, neither fluconazole nor voriconazole appear to affect or be affected by concomitant HIV protease inhibitor therapy [30,31]. However, levels of itraconazole (but not its metabolite hydroxyitraconazole) are increased when administered with the combination HIV protease inhibitor lopinavir/ritonavir [32], and a reduced dosage may be used. Posaconazole may act similarly.…”

Cushing Syndrome and Severe Adrenal Suppression Caused by Fluticasone and Protease Inhibitor Combination in an HIV-Infected Adolescent

“…Such reported interactions between protease inhibitors and medication classes which are also cytochrome p450 active include anticonvulsants, azole antifungals, and HMG coA reductase inhibitors. [22][23][24] The interaction described here between inhaled corticosteroids and PIs depends not only on the aforementioned p450 interaction, but also on a number of other factors including the dose, duration of therapy, inhaler delivery device, concurrent medications and conditions, and individual patient's glucocorticoid-receptor sensitivity. 12,21,25 The pharmacokinetic profile of fluticasone may help elucidate why it has been more frequently implicated in causing adrenal suppression and Cushing syndrome.…”