Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults and adolescents (over 12 years of age) with rupatadine 10 mg tablets.

Effects of other drugs on rupatadine

Co-administration with potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, nefazodone) should be avoided and co- medication with moderate CYP3A4 inhibitors (erythromycin, fluconazole, diltiazem) should be used with caution.

The concomitant administration of rupatadine 20 mg and ketoconazole or erythromycin increases the systemic exposure to rupatadine 10 times and 2-3 times respectively. These modifications were not associated with an effect on the QT interval or with an increase of the adverse reactions in comparison with the drugs when administered separately.

Interaction with grapefruit: The concomitant administration of grapefruit juice increased 3.5 times the systemic exposure of rupatadine. Grapefruit juice should not be taken simultaneously.

Effects of rupatadine on other drugs

Caution should be taken when rupatadine is co-administered with other metabolised drugs with narrow therapeutic windows since knowledge of the effect of rupatadine on other drugs is limited.

Interaction with alcohol: After administration of alcohol, a dose of 10 mg of rupatadine produced marginal effects in some psychomotor performance tests although they were not significantly different from those induced by intake of alcohol only. A dose of 20 mg increased the impairment caused by the intake of alcohol.

Interaction with CNS depressants: As with other antihistamines, interactions with CNS depressants cannot be excluded

Interaction with statins: Asymptomatic CPK increases have been uncommonly reported in rupatadine clinical trials. The risk of interactions with statins, some of which are also metabolised by the cytochrome P450 CYP3A4 isoenzyme, is unknown. For these reasons, rupatadine should be used with caution when it is coadministered with statins.

Interaction with midazolam: After the administration of 10 mg rupatadine in combination with 7.5 mg midazolam, an increase of exposure (Cmax and AUC) of midazolam was mildly higher observed. For this reason, rupatadine acts as a mild inhibitor of CYP3A4.