Tolterodine Itraconazole

A4 inhibitors - Patients receiving cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (erythromycin and clarithromycin), antifungal agents (ketoconazole, itraconazole, and miconazole), or cyclosporine or vinblastine should not receive doses of tolterodine greater than 1 mg twice/day (greater than 2 mg/day for ER capsules). 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

ANTIMUSCARINICS ANTIFUNGALS -ITRACONAZOLE, KETOCONAZOLE 1. i ketoconazole levels. 2. t darifenacin, solifenacin and tolterodine levels 1. 1 absorption 2. Inhibited metabolism 1. Watch for poor response to keto-conazole 2. Avoid co-administration of itraconazole, ketoconazole and these antimuscarinics. The US manufacturer of darifenacin recommends that its dose should not exceed 7.5 mg/day... 

ITRACONAZOLE TOLTERODINE t tolterodine level. Supratherapeutic levels may cause prolongation of the Q-T interval CYP3A4 is the major enzyme involved in the elimination of tolterodine in individuals with deficient CYP2D6 activity (poor metabolizers). Inhibition of CYP3A4 by triazoles in such individuals could cause dangerous t tolterodine levels Avoid co-administration... 

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. 

---