Rytmonorm Drug Interactions

A possible potentiation of drug side effects may occur when propafenone hydrochloride is taken in conjunction with local anesthetics (eg. pacemaker implantation, surgery or dental work) and other drugs which have an inhibitory effect on the heart rate and/or myocardinal contractility (eg. beta block-ers, tricyclic antidepressants).
Coadministration of propafenone hydrochloride with drugs metabolized by CYP2D6 (such as venlafaxine) might lead to increased levels of these drugs. Increases in propranolol, metoprolol, desipramine, cyclosporine, theophylline and digoxin plasma levels or blood levels have been reported during propafenone hydrochloride therapy.
Drugs that inhibit CYP2D6, CYP1A2 and CYP3A4, eg. ketoconazole, cimetidine, quinidine, erythromycin and grapefruit juice might lead to increased levels of propafenone hydrochloride. When propafenone hydrochloride is administered with inhibitors of these enzymes, the patients should be closely monitored and the dose adjusted accordingly.
Due to the potential for increased plasma concentrations, co-administration of ritonavir and propafenone hydrochloride is contraindicated (see Contraindications).
Combination therapy of amiodarone and propafenone hydrochloride can affect conduction and repolarization and lead to abnormalities that have the potential to be proarrhythmic. Dose adjustments of both compounds based on therapeutic response may be required.
No significant effects on the pharmacokinetics of propafenone or lidocaine have been seen following their concomitant use in patients. However, concomitant use of propafenone hydrochloride and intravenous lidocaine have been reported to increase the risks of central nervous system side effects of lidocaine.
Phenobarbital is a known inducer of CYP3A4. Response to propafenone hydrochloride therapy should be monitored during concomitant chronic phenobarbital use.
Concomitant use of propafenone hydrochloride and rifampicin may reduce the antiarrhythmic efficacy of propafenone hydrochloride as the result of a reduction in the propafenone plasma levels. Close monitoring of the clotting status in patients receiving concomitant oral anticoagulants (eg. phenprocoumon warfarin) is recommended as propafenone hydrochloride may enhance the efficacy of these drugs resulting in an increased prothrombin time.
Elevated levels of plasma propafenone may occur when propafenone hydrochloride is used concomitantly with SSRIs, such as fluoxetine and paroxetine. Concomitant administration of propafenone hydrochloride and fluoxetine in extensive metabolizers increased the S-propafenone Cmax and AUC by 39 and 50% and the R-propafenone Cmax and AUC by 71 and 50%. Lower doses of propafenone may be sufficient to achieve the desired therapeutic response.