Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Potential for other medicinal products to affect Inovelon tablets 
Other anti-epileptic medicinal products
Rufinamide concentrations are not subject to clinically relevant changes on co- administration with known enzyme inducing antiepileptic medicinal products.

For patients on Inovelon tablets treatment who have administration of valproic acid (as sodium) initiated, significant increases in rufinamide plasma concentrations may occur. Therefore, consideration should be given to a dose reduction of Inovelon tablets in patients who are initiated on valproic acid ( a s s o d i u m ) therapy (see Section 4.2).

The addition or withdrawal of these medicinal products or adjusting of the dose of these medicinal products during Inovelon tablets therapy may require an adjustment in dosage of Inovelon tablets (see section 4.2).

No significant changes in rufinamide concentration are observed following co- administration with lamotrigine, topiramate or benzodiazepines.

Potential for Inovelon tablets to affect other medicinal products 
Other anti-epileptic medicinal products
The pharmacokinetic interactions between rufinamide and other anti-epileptic medicinal products have been evaluated in patients with epilepsy using population pharmacokinetic modelling.
Rufinamide appears not to have a clinically relevant effect on carbamazepine, lamotrigine, phenobarbital, topiramate, phenytoin or valproic acid (as sodium) steady state concentrations.

Oral contraceptives
Co-administration of rufinamide 800 mg twice daily and a combined oral contraceptive (ethinyloestradiol 35 μg and norethindrone 1 mg) for 14 days resulted in a mean decrease in the ethinyl estradiol AUC0-24 of 22% and in norethindrone AUC0-24 of 14%. Studies with other oral or implant contraceptives have not been conducted. Women of child-bearing potential using hormonal contraceptives are advised to use an additional safe and effective contraceptive method (see sections 4.4 and 4.6).

Cytochrome P450 enzymes
Rufinamide is metabolised by hydrolysis, and is not metabolised to any notable degree by cytochrome P450 enzymes. Furthermore, rufinamide does not inhibit the activity of cytochrome P450 enzymes (see section 5.2). Thus, clinically significant interactions mediated through inhibition of cytochrome P450 system by rufinamide are unlikely to occur.
Rufinamide has been shown to induce the cytochrome P450 enzyme CYP3A4 and may therefore reduce the plasma concentrations of substances which are metabolised by this enzyme. The effect was modest to moderate. The mean CYP3A4 activity, assessed as clearance of triazolam, was increased by 55% after 11 days of treatment with rufinamide 400 mg twice daily. The exposure of triazolam was reduced by 36%. Higher rufinamide doses may result in a more pronounced induction. It may not be excluded that rufinamide may also decrease the exposure of substances metabolised by other enzymes, or transported by transport proteins such as P-glycoprotein.

It is recommended that patients treated with substances that are metabolised by the CYP3A4 enzyme system are to be carefully monitored for two weeks at the start of, or after the end of treatment with Inovelon tablets, or after any marked change in the dose. A dose adjustment of the concomitantly administered medicinal product may need to be considered. These recommendations should also be considered when rufinamide is used concomitantly with substances with a narrow therapeutic window such as warfarin and digoxin.

A specific interaction study in healthy subjects revealed no influence of rufinamide at a dose of 400 mg twice daily on the pharmacokinetics of olanzapine, a CYP1A2 substrate.

No data on the interaction of rufinamide with alcohol are available.