Tolterodine Protease inhibitors

TOLTERODINE PROTEASE INHIBITORS Possibly t adverse effects, including ariythmias, with protease inhibitors Inhibition of CYP2D6- and 3A4-mediated metabolism of tolterodine Avoid co-administration... 

Drugs that may affect fluconazole include cimetidine, hydrochlorothiazide, and rifampin. Drugs that may be affected by fluconazole include alfentanil, benzodiazepines, buspirone, carbamazepine, cisapride, oral contraceptives, corticosteroids, cyclosporine, haloperidol, HMG-CoA reductase inhibitors, losartan, nisoldipine, phenytoin, protease inhibitors, rifabutin, sirolimus, sulfonylureas, tacrolimus, theophylline, tolterodine, tricyclic antidepressants, vinca alkaloids, warfarin, zidovudine, and zolpidem. 

Ketoconazole can increase tolterodine levels in those who are deficient in the cytochrome P450 isoenzyme CYP2D6 (poor metab-olisers). The manufacturers of tolterodine currently say that potent CYP3A4 inhibitors such as clarithromycin, erythromycin, itraconazole and ketoconazole, and protease inhibitors should be used with caution or avoided because of a risk of increased tolterodine effects. 

The UK manufacturers consider that this increase in levels represents a risk of overdose in poor CYP2D6 metabolisers. Consequently, they do not recommend the use of potent CYP3A4 inhibitors (they name clarithromycin, erythromycin, ketoconazole, and itraconazole, and protease inhibitors) with tolterodine in any patient (note that metaboliser status is rarely known). However, the US manufacturers recommend only that the dose of tolterodine be reduced to 1 mg twice daily in patients currently taking drugs that are potent inhibitors of CYP3A4, and this seems the more sensible advice. It may be prudent to assess experience of adverse effects in these patients, and to reduce the dose further or withdraw the drug if it is not tolerated. 

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See also in sourсe #XX -- [ ]

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