Tolterodine Clarithromycin

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). 

TOLTERODINE ANTIBIOTICS - CLARITHROMYCIN, ERYTHROMYCIN t tolterodine levels Inhibition of CYP3A4-mediated metabolism Avoid co-administration (manufacturers recommendation)... 

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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