Is there a risk for an interaction between Atarax (hydroxyzine) and Detrusitol (tolterodine)?/nA 32

Fråga: Is there a risk for an interaction between Atarax (hydroxyzine) and Detrusitol (tolterodine)? A 32-year-old woman is treated with hydroxyzine. Addition of tolterodine is being considered.

Sammanfattning: No reports of interaction between tolterodine and hydroxyzine were found in the literature. There is a theoretical risk of potentiated anticholinergic effects (urinary retention, hypotension, tachycardia, dry mouth, etc) if the drugs are used concurrently. In young patients, as in this case, this risk should not be of major concern. A metabolic interaction between the two drugs is unlikely to occur.

Svar: No data on any interaction between tolterodine and hydroxyzine were found in the literature.

Tolterodine exerts its therapeutic effects through blockade of muscarine receptors. Hydroxyzine also has anticholinergic properties. By using a combination of hydroxyzine and tolterodine the therapeutic effects and adverse effects of tolterodine could thus theoretically be potentiated.

Both tolterodine and hydroxyzine undergo metabolism in the liver. Tolterodine is mainly metabolised by CYP2D6 to the pharmacologically active metabolite 5-hydroxytolterodine (1). In individuals lacking the CYP2D6 enzyme (poor metabolisers), tolterodine is dealkylated by CYP3A4 (1). Hydroxyzine is metabolised to cetrizine, which is pharmacologically active, and to other metabolites (2). The metabolism of hydroxyzine is presumably catalyzed by the cytochrome P450-system, the specific isoenzyme responsible is not known.

Available data do not indicate that there is a major risk of a metabolic interaction between the two drugs. Tolterodine has in healthy volunteers not shown any significant inhibitory effect on those microsomal enzymes that most frequently catalyse hepatic drug metabolism (ie CYP1A2, 2C9, 2C19, 2D6 and 3A4) (3). In an in vitro study it was shown that cetrizine in therapeutic concentrations had no inhibitory effect on CYP2D6 and CYP3A4 (4), the major cytochrome P450s involved in tolterodine metabolism. Therefore, a metabolic interaction between hydroxyzine and tolterodine is not likely.