Antifungals

Abstract

Gastric irritation and cephalea following off-label use and lack of efficacy: 8 case reports In a study, eight adult men aged 26–49 years, who had been treated at a hospital in Mexico for CNS infections due to Cryptococcus neoformans (C. neoformans) were described, who exhibited lack of efficacy during treatment with amphotericin B, amphotericin-B-liposomal or fluconazole for cryptococcal meningitis caused by C. neoformans. Additionally, all these eight patients received off-label treatment with posaconazole for cryptococcal meningitis caused by C. neoformans; of them, seven patients developed gastric irritation (5 patients) or cephalea (2 patients) following off-label treatment with posaconazole for cryptococcal meningitis caused by C. neoformans [not all dosages and routes stated ]. All adult men were diagnosed with cryptococcal meningitis caused by C. neoformans. Hence, they started receiving standard antifungal therapy with amphotericin-B [amphotericin B deoxycholate] (7 men), or amphotericin-B-liposomal [amphotericin colloidal dispersion] (1 man). However, cryptococcal meningitis was found to be refractory to the antifungal therapy, suggesting a lack of efficacy of amphotericin B oramphotericin-B-liposomal. Additionally, 3/8 men developed an unspecified intolerance to amphotericin-B and fluconazole (2 men) or amphotericin-B (1 man). Therefore, the antifungal treatment was replaced by fluconazole (4 men). However, cryptococcal meningitis was found to be refractory to fluconazole also. Thus, standard antifungal therapy was replaced with off-label oral posaconazole 400mg twice daily suspension [Schering Plough Research Institute, USA] in all eight men. They received amphotericin-B for a total of 20–75 days, fluconazole for a total of 7–33 days or amphotericin-B-liposomal for a total of 10 days. The posaconazole medication was administered with food or nutritional liquids. Within 2 weeks of initiation of posaconazole, an improvement in the signs and symptoms of CNS fungal infection was noted (7 men). One man was excluded due to the addition of another unspecified antifungal drug, and other 7 men completed the off-label therapy for a total duration of 28 days. However, 7/8 men developed posaconazole-related adverse reactions, such as gastric irritation (5 men), cephalea (1 man) or intense cephalea (1 man) [time to reaction onsets and outcomes not stated].