Voriconazole adverse effects

Adverse Effects. Skin rashes and vision disturbances (blurred vision, seeing bright spots) are common during voriconazole administration, but these side effects are usually transient and fairly uneventful. Serious problems, such as liver toxicity and cardiac arrhythmias, may occur in susceptible patients. 

FLUCONAZOLE, ITRACONAZOLE, KETOCONAZOLE, VORICONAZOLE (POSSIBLY POSACONAZOLE) VINCA ALKALOIDS -VINBLASTINE, VINCRISTINE, VINORELBINE t adverse effects of vinblastine and vincristine Inhibition of CYP3A4-mediated metabolism. Also inhibition of P-gp efflux of vinblastine Monitor FBCs and watch for early features of toxicity (pain, numbness, tingling in the fingers and toes, jaw pain, abdominal pain, constipation, ileus). Consider selecting an alternative drug... 

VORICONAZOLE OMEPRAZOLE Possible t efficacy and adverse effects of both drugs 1. Inhibition of voriconazole metabolism via CYP2C19 and CYP3A4 2. Inhibition of metabolism of omeprazole 1. No dose adjustment of voriconazole is recommended 2. Halve the omeprazole dose... 

Visual adverse events, in particular enhanced brightness of light and color, are common with voriconazole (11). These visual adverse effects are transient and reversible. So far, comprehensive ophthalmological investigations have not shown any morphological correlates or longterm visual sequelae in any patient. 

The manufacturer in the US contraindicates the combination of voriconazole and rifabutin. However, the UK manufacturer permits concurrent use if the benefits outweigh the risks. If used together, it is recommended that the oral dose of voriconazole be increased from 200 mg twice daily to 350 mg twice daily (and from 100 to 200 mg twice daily in patients under 40 kg). The intravenous dose should also be increased from 4 to 5 mg/kg twice daily. Importantly, the manufacturer advises careful monitoring for rifabutin adverse effects (e.g. check full blood counts, monitor for uveitis). 

Ketoconazole causes a small to moderate rise in serum carbamazepine levels. A marked rise in carbamazepine levels has been seen in two patients taking fluconazole, with toxicity in one. Adverse effects were seen in another patient when carbamazepine was given with miconazole. Carbamazepine may markedly reduce the levels of itraconazole and possibly voriconazole, and is predicted to lower the levels of posaconazole. 

The interaction between phenytoin and voriconazole is established. The UK manufacturers say that concurrent use of voriconazole and phenytoin should be avoided unless the benefits outweigh the risks. If used together, the manufacturers recommend careful monitoring of phenytoin levels and adverse effects, and doubling the dose of oral voriconazole (from 200 to 400 mg twice daily and from 100 mg to 200 mg twice daily in patients less than 40 kg) or increasing the dose of intravenous voriconazole (from 4 to 5 mg/kg twice daily). 

Information seems to be limited to these reports. Neither fluconazole nor ketoconazole normally appears to interact to a relevant extent in most patients. However, it seems that very occasionally some changes occur so bear this interaction in mind in the case of unexpected changes in theophylline levels, adverse effects or uncontrolled symptoms. Other azole antifungals such as itraconazole, posaconazole and voriconazole, which are substrates for and inhibitors of CYP2C19, CYP2C9, and/or CYP3A4, are also unlikely to interact with theophylline. 

Voriconazole has often been reported to have caused photosensitivity [36 ], and this adverse effect has been linked to a risk of tumors in light-exposed areas. The EIDOS and DoTS descriptions of this reaction are shown in Eigure 1. 

Observational studies Of 72 patients undergoing allogeneic transplantation who were given voriconazole as antifungal prophylaxis starting from 2 days before transplantation and continuing until withdrawal of immunosuppression, 10 required interruption of voriconazole therapy because of adverse effects hepatotoxicity ( = 6), QT interval prolongation (n = 1), or other adverse effects ( = 4) [68]. 

Perbet S, Blondonnet R, Gu in R, Cayot-Constantin S, Constantin JM. Voriconazole-induced bradycardia without QT interval prolongation a possible non-concentration-dependent adverse effect. Intensive Care Med 2013 39(3) 531-2. 

Tilidine The effect of voriconazole 400 mg on the pharmacokinetics and analgesic effects of tilidine 100 mg have been investigated in 16 healthy volunteers in a placebo-controlled study f49 ]. Voriconazole caused a 20-fold increase in the serum AUC of tilidine and the AUC of nortilidine increased 2.5-fold the serum concentrations of bisnor-tilidine were much reduced. The onset of analgesic activity occurred later with voriconazole, concordant with the prolonged t ax of nortilidine from 0.78 to 2.5 hours, due to additional inhibition of nortilidine metabolism to bisnortilidine. After voriconazole the AUC under the pain withdrawal versus time curve was reduced compared, mainly because of a shorter withdrawal time. Thus, voriconazole significantly inhibited the sequential metabolism of tilidine, with increased exposure to the active metabolite, nortilidine. Furthermore, the incidence of adverse events was almost doubled after voriconazole and tilidine. 

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