Eletriptan Fluconazole

CYP3A4 enzyme. A clinical study has shown that coadministration of eletriptan with ketoconazole, erythromycin, verapamil, and fluconazole increased the Cmax3> cl... 

Ketoconazole and fluconazole increase the AUC of eletriptan by about sixfold and twofold, respectively. Almotriptan is less affected, and ketoconazole only raises its AUC by about 60%. Itraconazole is predicted to interact in the same way as ketoconazole. 

A pharmacokinetic study by the manufacturers of eletriptan found that ketoconazole 400 mg increased the maximum serum levels of eletriptan 2.7-fold, the AUC 5.9-fold and prolonged its half-life from 4.8 to 8.3 hours. Fluconazole caused a lesser 1.4-fold increase in the maximum serum levels of eletriptan, and a twofold increase in its AUC. ... 

Ketoconazole is a potent inhibitor of the cytochrome P450 isoenzyme CYP3A4, by which eletriptan is metabolised. Fluconazole is a less potent inhibitor of CYP3A4, and therefore has a more modest effect. Almotriptan is also metabolised by CYP3A4, but as this is not the only route of metabolism, and therefore inhibition of CYP3A4 by ketoconazole has a less dramatic effect on its levels. 

Itraconazole, which is also a potent inhibitor of CYP3A4, has been predicted to interact in the same way as ketoconazole. " In addition, the US manufacturers recommend that eletriptan should not be given within 72 hours of itraconazole and ketoconazole. Fluconazole is a less potent inhibitor of CYP3A4 and therefore may be used with caution. Other triptans would be expected to have little or no interaction with the azoles as they are not predominantly metabolised by CYP3A4 (see Table 16.2 , (p.597)). 

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