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| __NOTOC__
| | #REDIRECT [[Procainamide#Drug Interactions]] |
| {{Propafenone}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Dosage Forms and Strengths==
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| ===7.1 CYP2D6 and CYP3A4 Inhibitors===
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| Drugs that inhibit CYP2D6 (such as [[desipramine]], [[paroxetine]], [[ritonavir]], or [[sertraline]]) and CYP3A4 (such as [[ketoconazole]], [[ritonavir]], [[saquinavir]], [[erythromycin]], or grapefruit juice) can be expected to cause increased plasma levels of propafenone. The combination of CYP3A4 inhibition and either CYP2D6 deficiency or CYP2D6 inhibition with administration of propafenone may increase the risk of adverse reactions, including proarrhythmia. Therefore, simultaneous use of RYTHMOL with both a CYP2D6 inhibitor and a CYP3A4 inhibitor should be avoided [see Warnings and Precautions (5.4), Dosage and Administration (2)].
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| <u>Amiodarone</u>: Concomitant administration of propafenone and [[amiodarone]] can affect conduction and repolarization and is not recommended.
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| <u>Cimetidine</u>: Concomitant administration of propafenone immediate-release tablets and [[cimetidine]] in 12 healthy subjects resulted in a 20% increase in steady-state plasma concentrations of propafenone.
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| <u>Fluoxetine</u>: Concomitant administration of propafenone and fluoxetine in extensive metabolizers increased the S-propafenone Cmax and AUC by 39% and 50%, respectively, and the R propafenone Cmax and AUC by 71% and 50%, respectively.
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| <u>Quinidine</u>: Small doses of [[quinidine]] completely inhibit the CYP2D6 hydroxylation metabolic pathway, making all patients, in effect, slow metabolizers [see Clinical Pharmacology (12)]. Concomitant administration of quinidine (50 mg 3 times daily) with 150 mg immediate-release propafenone 3 times daily decreased the clearance of propafenone by 60% in extensive metabolizers, making them slow metabolizers. Steady-state plasma concentrations more than doubled for propafenone, and decreased 50% for 5-OH-propafenone. A 100-mg dose of quinidine tripled steady-state concentrations of propafenone. Avoid concomitant use of propafenone and [[quinidine]].
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| <u>Rifampin</u>: Concomitant administration of [[rifampin]] nd propafenone in extensive metabolizers decreased the plasma concentrations of propafenone by 67% with a corresponding decrease of 5-OH-propafenone by 65%. The concentrations of norpropafenone increased by 30%. In slow metabolizers, there was a 50% decrease in propafenone plasma concentrations and an increase in the AUC and Cmax of norpropafenone by 74% and 20%, respectively. Urinary excretion of propafenone and its metabolites decreased significantly. Similar results were noted in elderly patients: Both the AUC and Cmax of propafenone decreased by 84%, with a corresponding decrease in AUC and Cmax of 5-OH‑propafenone by 69% and 57%, respectively.
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| ===7.2 Digoxin===
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| Concomitant use of propafenone and [[digoxin]] increased steady-state serum [[digoxin]] xposure (AUC) in patients by 60% to 270%, and decreased the clearance of [[digoxin]] y 31% to 67%. Monitor plasma digoxin levels of patients receiving propafenone and adjust [[digoxin]] dosage as needed.
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| ===7.3 Warfarin===
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| The concomitant administration of propafenone and [[warfarin]] increased [[warfarin ]]plasma concentrations at steady state by 39% in healthy volunteers and prolonged the prothrombin time (PT) in patients taking warfarin. Adjust the [[warfarin ]]dose as needed by monitoring INR (international normalized ratio).
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| ===7.4 Orlistat===
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| [[Orlistat]] may limit the fraction of propafenone available for absorption. In postmarketing reports, abrupt cessation of orlistat in patients stabilized on propafenone has resulted in severe adverse events including convulsions, atrioventricular block, and acute circulatory failure.
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| ===7.5 Beta-Antagonists===
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| Concomitant use of propafenone and propranolol in healthy subjects increased propranolol plasma concentrations at steady state by 113%. In 4 patients, administration of metoprolol with propafenone increased the metoprolol plasma concentrations at steady state by 100% to 400%. The pharmacokinetics of propafenone was not affected by the coadministration of either propranolol or metoprolol. In clinical trials using propafenone immediate-release tablets, subjects who were receiving beta-blockers concurrently did not experience an increased incidence of side effects.
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| ===7.6 Lidocaine===
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| No significant effects on the pharmacokinetics of propafenone or lidocaine have been seen following their concomitant use in patients. However, concomitant use of propafenone and lidocaine has been reported to increase the risks of central nervous system side effects of lidocaine.
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| <ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = RYTHMOL SR (PROPAFENONE HYDROCHLORIDE) CAPSULE, EXTENDED RELEASE [GLAXOSMITHKLINE LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8bb1bc4a-a019-49c8-af81-be899822428f | publisher = | date = | accessdate = 13 March 2014 }}</ref>
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| ==References==
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| {{Reflist}}
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| [[Category:Antiarrhythmic agents]]
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| [[Category:Ketones]]
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| [[Category:Phenol ethers]]
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| [[Category:Alcohols]]
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| [[Category:Amines]]
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| [[Category:Sodium channel blockers]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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