Paroxetine Flecainide

CYP2C19 CYP2D6 diazepam, imipramine, 5-mephenytoin, omeprazol, proguanil, propranolol codeine, debrisoquine, dextromethorphan, flecainide, paroxetine, perphenazine, thioridazine carbamazepine, rifampicin cimetidine, felbamate fluoxetine, paroxetine, quinidine... 

Inhibitors codeine, encainide, flecainide, fluoxetine, haloperidol, hydrocodone, 4-methoxy-amphetamine, metoprolol, mexiletine, oxycodone, paroxetine, propafenone, propoxyphene, risperidone, selegiline (deprenyl), thioridazine, most tricyclic antidepressants, timolol Fluoxetine, haloperidol, paroxetine, quinidine... 

IMATINIB 1. ANTIARRHYTHMICS -flecainide, mexiletine, propafenone 2. ANTIDEPRESSANTS - fluoxetine, paroxetine, TCAs, trazodone, venlafaxine 3. ANTIPSYCHOTICS -clozapine, haloperidol, perphenazine, risperidone, thioridazine 4. BETA-BLOCKERS - metoprolol, propanolol, timolol 5. DONEPEZIL 6. METHAMPHETAMINE Imatinib may cause t plasma concentrations of these drugs, with a risk of toxic effects Inhibition of CYP2D6-mediated metabolism of these drugs Watch for early features of toxicity of these drugs... 

Ajmaline, ajamlicine, flecainide, fluoxetine, isoniazid, ketoconazole, lobeline, nefazodone, paroxetine, (7 )-propaphenooe, quinidine, ritonavir, "statins," yohimbine, venlafaxine... 

Potentially clinically significant interactions include the tendency for fluvoxamine to increase circulating concentrations of oxidatively metabolized benzodiazepines, clozapine, theophylline, and warfarin. Sertraline and fluoxetine can increase levels of benzodiazepines, clozapine, and warfarin. Paroxetine increases levels of clozapine, theophylline, and warfarin. Fluoxetine also potentiates tricyclic antidepressants and some class 1C antiarrhythmics with a narrow therapeutic index (including encainide, flecainide, and propafenone). Nefazodone potentiates benzodiazepines other than lorazepam and oxazepam. 

A 69-year-old woman developed confusion and paranoia over several days. She was taking carvedilol 12 mg bd, warfarin 2 mg/day, folic add 1 mg/day, levothyroxine 100 micro-grams/day, pantoprazole 40 mg/day, paroxetine 40 mg/day, and flecainide 100 mg bd. The flecainide had been started 2 weeks before. The plasma flecainide concentration was 1.36 mg/1. Paroxetine was withdrawn and the dosage of flecainide was reduced to 50 mg bd. Her delirium resolved 3 days later. 

Flecainide is a substrate and paroxetine an inhibitor of CYP2D6. Flecainide-associated delirium has been previously described. 

Tsao YY, Gugger JJ. Delirium in a patient with toxic flecainide plasma concentrations the role of a pharmacokinetic drug interaction with paroxetine. Ann Pharmacother 2009 43(7) 1366-9. 

Drug-drug interactions Flecainide Fleca-inide, a class 1C antidysrhythmic agent, is metabolized by CYP2D6. In a study of the interaction of the CYP2D6 10 allele and paroxetine in an open crossover study in healthy Korean subjects, paroxetine significantly increased the AUC of flecainide and... 

Delirium occurred in a 69-year-old woman who had been taking paroxetine regularly for 5 years after she took flecainide for atrial fibrillation for 2 weeks her serum flecainide concentration was markedly raised and the delirium resolved 3 days after flecainide withdrawal... 

A 67-year-old patient taking paroxetine 40 mg/ day developed confusion and paranoia after taking flecainide 200 mg/day for 2 weeks. The plasma flecainide concentration was 1360 mg/1 (usual target range 200-1000) the symptoms subsided after paroxetine was withdrawn and the dose of flecainide was reduced [68 ]. 

The effects of CYP2D6 genetic polymorphisms on the pharmacokinetics of a single oral dose of flecainide and on the extent of its interaction with paroxetine have been investigated in an open study in 21 healthy Korean volunteers [69 ]. The AUC, terminal half-life, and mean residence time increased significantly after paroxetine in those with the CYP2D6 10 allele, which is common among Asians. 

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