Voriconazole/retinol interaction
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First report of an interaction, leading to visual disturbance and photosensitivity in paediatric patients: 6 case reports Six patients with cystic fibrosis developed visual disturbances and photosensitivity (five patients), during treatment with voriconazole for chronic necrotising pulmonary aspergillosis and retinol [see table for patient characteristics].* All six patients were receiving retinol [vitamin A] 10 000 IU/day [indication and duration of treatment to reaction onset not clearly stated], and continuous voriconazole for 6–25 months; their serum voriconazole concentrations ranged from 0.24 to 8.04 mg/L (therapeutic 1–5.5 mg/L). All six patients developed visual disturbances, and all except patient 4 experienced photosensitivity [not all outcomes stated].
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cutaneous rashes and photosensitivity encountered with voriconazole usage." * These patients were retrospectively identified. Cheng MP, et al. Voriconazole inhibition of vitamin A metabolism: Are adverse events increased in cystic fibrosis patients?. Pediatric Pulmonology 45: 661-666, No. 7, Jul 2010. Available from: URL: http://dx.doi.org/10.1002/ppul.21234 803033756 Canada
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Editorial comment: A search of AdisBase, Medline and Embase did not reveal any previous case reports of an interaction between voriconazole and retinol. The WHO ADR database contained no reports concerning the concomitant use of retinol and voriconazole.
Patient characteristics Voriconazole Pt/sex/age (y) 1/M/7
2/M/16 3/F/16
4/M/17 5/F/18 6/F/18 a
dosage
route
durationa
100 mg/day 200 mg/day 300 mg/day 400mg twice daily 400mg twice daily 100 mg/day 300 mg/day 150 mg/day 350mg twice daily 200mg twice daily 400mg twice daily 175mg twice daily
oral oral oral IV oral oral oral oral IV oral oral IV
22 months 1 month 1 month 6 weeks 8 months 3 months 2 weeks 4 months 6 months 19 months 6 months 8 months
Times to onset only stated for patients 1 and 3 (see text).
Two patients were described in detail: Patient 1 received oral voriconazole 100 mg/day for 22 months, from the age of 6 years. Treatment was resumed at 200 mg/day three months after its cessation, and increased to 300 mg/day one month later. He developed progressive erythema a few days after the dosage increase, followed by desquamation and mild averseness to light with 1 week. Over 3 weeks, his upper chest and thorax became tender to palpation, facial erythema and lip blisters developed, and he refused to enter heavily lit rooms. Voriconazole was replaced with posaconazole, and his skin and light-associated symptoms resolved within 2 weeks; his concomitant medication included a retinol-containing multivitamin [Flintstone]. Patient 3 started receiving oral voriconazole 100 mg/day, increased to 300 mg/day after 1 month. She developed blurred vision with decreased visual acuity soon after the dosage increase; tunnel vision with marked reduction of her visual field occurred within the first week. Other symptoms included scotomas, and marked facial erythema following sun exposure. Two weeks after the dosage increas
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