Ketoconazole Eletriptan

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

A4/3A5 Midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, triazolam Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Rifampin, carbamazepine... 

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. 

Although studies are limited these interactions are established. In the study with almotriptan and ketoconazole adverse events were not significantly altered, and so no almotriptan dosage adjustment is considered necessary when using this combination. Ketoconazole dramatically raises eletriptan levels, and therefore the manufacturers advise that concurrent use should be avoided. 

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)). 

The manufacturers state that the concurrent use of eletriptan and ritonavir, indinavir, or nelfinavir should be avoided, because these protease inhibitors are potent inhibitors of the cytochrome P450 isoenzyme CYP3A4, an enzyme involved in the metabolism of eletriptan. Concurrent use would therefore be expected to markedly increase levels of eletriptan. In addition, the US manufacturers recommend that eletriptan should not be given within 72 hours of ritonavir and nelfinavir. This predicted interaction is based on the known interaction with eiythromycin , (p.604) and ketoconazole , (p.601). Similar predictions are made by the manufacturers of almotriptan, and they advise caution with the use of ritonavir. ... 

---