Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
Class I anti-arrhythmics: Tambocor tablets should not be administered concomitantly with other class I antiarrythmics. Concomitant use of quinidine can decrease Tambocor tablets clearance by 23%.
Class II anti-arrhythmics: the possibility of additive negative inotropic effects of class II anti- arrhythmics i.e. beta-blockers, and other cardiac depressants with Tambocor tablets should be recognised.
Class III anti-arrhythmics: if Tambocor tablets is given in the presence of amiodarone, the usual Tambocor tablets dosage should be reduced by 50% and the patient monitored closely for adverse effects. Plasma level monitoring is strongly recommended in these circumstances.

Class IV anti-arrhythmics: the use of Tambocor tablets with calcium channel blockers e.g.
verapamil should be considered with caution.

Life-threatening or even lethal adverse events due to interactions causing increased plasma concentrations may occur (see section 4.9). Flecainide is metabolized by CYP2D6 to a large extent, and concurrent use of drugs inhibiting (e.g. antidepressants, neuroleptics, propranolol, ritonavir, some antihistamines) or inducing (e.g. phenytoin, phenobarbital, carbamazepine) this iso-enzyme can increase or decrease plasma concentrations of flecainide, respectively (see below).

Hypokalaemia but also hyperkalaemia or other electrolyte disturbances should be corrected before administration of Tambocor tablets. Hypokalaemia may result from the concomitant use of diuretics, corticosteroids or laxatives.

Antivirals: plasma concentrations are increased by ritonavir and fixed-combination products containing ritonavir (increased risk of ventricular arrhythmias, avoid concomitant use).

Anti-malarials: quinine increases plasma concentration of Tambocor tablets.

Anti-histamines: increased risk of ventricular arrhythmias with mizolastine and terfenadine (avoid concomitant use).

Anti-depressants: fluoxetine, paroxetine and other antidepressants increase plasma concentration; increased risk of arrhythmias with tricyclics; manufacturer of reboxetine advises caution.

Anti-epileptics: limited data in patients receiving known enzyme inducers (phenytoin, phenobarbital, carbamazepine) indicate only a 30% increase in the rate of flecainide elimination.

Anti-psychotics: clozapine – increased risk of arrhythmias.

Antifungals: terbinafine may increase plasma concentrations of flecainide resulting from its inhibition of CYP2D6 activity.

Diuretics: Class effect due to hypokalaemia giving rise to cardiaotoxicity.

H2 antihistamines (for the treatment of gastric ulcers): The H2 antagonist cimetidine inhibits metabolism of flecainide. . In healthy subjects receiving cimetidine (1g daily) for one week, the AUC of flecainide increased by about 30% and the half-life increased by about 10%.
Anti-smoking aids: Co-administration of bupropion (metabolised by CYP2D6) with Tambocor tablets should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication. If bupropion is added to the treatment regimen of a patient already receiving Tambocor tablets, the need to decrease the dose of the original medication should be considered.

Cardiac glycosides: Tambocor tablets acetate can cause the plasma digoxin level to rise by about 15%, which is unlikely to be of clinical significance for patients with plasma levels within the therapeutic range. It is recommended that the digoxin plasma level in digitalised patients should be measured not less than six hours after any digoxin dose, before or after administration of Tambocor tablets.

Anticoagulants: The treatment with Tambocor tablets is compatible with use of oral anti- coagulants.