Rufinamide

Strong CYP3A4 inducer may reduce plasma macimorelin concentrations and lead to false positive test results. Discontinue prior to use.

May decrease plasma concentrations of COCs and potentially diminish effectiveness or increase breakthrough bleeding.

Carbamazepine decreases rufinamide concentration by 19-26% and rufinamide decreases carbamazepine by 7-13%.

Induces CYP3A4 and may decrease plasma concentrations of desogestrel and ethinyl estradiol, potentially diminishing contraceptive effectiveness and increasing breakthrough bleeding.

Patients stabilized on rufinamide should begin valproate therapy at a low dose and titrate to clinically effective dose.

May decrease systemic concentrations of hormonal contraceptives and diminish effectiveness or increase breakthrough bleeding.

May decrease plasma concentrations of etonogestrel and diminish contraceptive effectiveness or increase breakthrough bleeding.

CYP3A4 enzyme inducer that may decrease plasma concentrations of etonogestrel and ethinyl estradiol, potentially diminishing contraceptive effectiveness or increasing breakthrough bleeding.

Induces CYP3A4, may decrease plasma concentrations of CHCs and potentially diminish effectiveness or increase breakthrough bleeding.

Rufinamide decreases lamotrigine levels by 7-13%. Monitor lamotrigine concentrations and adjust dose if needed.

Rufinamide induces CYP3A4 and may decrease plasma concentrations of COCs, potentially diminishing contraceptive effectiveness or increasing breakthrough bleeding.

Induces CYP3A4, may decrease plasma concentrations of COCs and diminish effectiveness or increase breakthrough bleeding.

Metabolic enzyme inducer that may decrease plasma concentrations of levonorgestrel and ethinyl estradiol, potentially diminishing contraceptive effectiveness or increasing breakthrough bleeding.

Moderate and weak CYP3A4 inducers include, for example: amprenavir, aprepitant, armodafinil, bosentan, efavirnenz, etravirine, Echinacea, modafinil, nafcillin, pioglitazone, prednisone, rufinamide, and vemurafenib.

Enzyme inducer that may decrease plasma concentrations of CHCs and potentially diminish effectiveness or increase breakthrough bleeding.

May decrease systemic concentrations of norethindrone and potentially diminish contraceptive effectiveness or increase breakthrough bleeding.

Enzyme inducer that may decrease plasma concentrations of COCs and potentially diminish contraceptive effectiveness or increase breakthrough bleeding.

May decrease plasma concentrations of COCs and diminish contraceptive effectiveness or increase breakthrough bleeding.

Enzyme inducer that may decrease plasma concentrations of norethindrone and ethinyl estradiol, potentially diminishing contraceptive effectiveness or increasing breakthrough bleeding.

May decrease plasma concentrations and efficacy of contraceptive; may increase breakthrough bleeding.

Rufinamide may reduce effectiveness of hormonal contraceptives; additional non-hormonal contraception recommended.

Phenobarbital decreases rufinamide concentration by 25-46% and rufinamide increases phenobarbital by 8-13%.

Phenytoin decreases rufinamide concentration by 25-46% and rufinamide increases phenytoin by 7-21% with potential for greater exposure due to phenytoin's non-linear pharmacokinetics.

Primidone decreases rufinamide concentration by 25-46%.

Metabolic enzyme inducer that may decrease systemic concentrations of estrogen and/or progestin, potentially diminishing contraceptive effectiveness.

Valproate increases rufinamide concentration by 16-70%; lower starting dose of rufinamide recommended (10 mg/kg/day pediatric, 400 mg/day adults).

Valproate increases rufinamide concentrations. Patients stabilized on rufinamide should begin valproate therapy at a low dose and titrate to clinically effective dose.

Patients stabilized on rufinamide should begin valproate therapy at a low dose and titrate to clinically effective dose.

Benzodiazepines have no effect on rufinamide concentration.

No significant pharmacokinetic interaction between rufinamide and topiramate.

Rufinamide: Based on a population pharmacokinetic analysis, rufinamide clearance was decreased by valproate. Rufinamide concentrations were increased by <16% to 70%, dependent on concentration of valproate (with the larger increases being seen in pediatric patients at high doses or concentrations of valproate). Patients stabilized on rufinamide before being prescribed valproate should begin valproate therapy at a low dose, and titrate to a clinically effective dose [see Dosage and Administration (2.6)].

Rufinamide Based on a population pharmacokinetic analysis, rufinamide clearance was decreased by valproate. Rufinamide concentrations were increased by <16% to 70%, dependent on concentration of valproate (with the larger increases being seen in pediatric patients at high doses or concentrations of valproate). Patients stabilized on rufinamide before being prescribed valproate should begin valproate therapy at a low dose, and titrate to a clinically effective dose [see Dosage and Administration (2.5)].

Based on in vivo drug interaction studies with triazolam and oral contraceptives, rufinamide is a weak inducer of the CYP 3A4 enzyme and can decrease exposure of drugs that are substrates of CYP 3A4. • Co-administration and pre-treatment of rufinamide (400 mg twice daily) and triazolam resulted in a 37% decrease in AUC and a 23% decrease in C max of triazolam, a CYP 3A4 substrate.

Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3.

Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3 .