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CLINICAL STATEMENTS AND GUIDELINES

January 2, 2024 Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 e80

Joglar et al 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation

Table 23.  Specific Drug Therapy for Maintenance of Sinus Rhythm in Patients With AF

Drug Loading Dose Maintenance Dose Primary Route(s) of Elimination Elimination Half-Life Mechanism of Action Major Adverse Effects Important Pharmacokinetic Drug Interactions Amiodarone Total loading dose 6-10 g, given 400-800 mg daily in 2-4 divided doses for 1-4 wk 200 mg once daily Liver metabolism Biliary excretion 14-59 d Inhibits IKr, IKs, INa, IKur, Ito, ICa-L, IKAch Noncompetitive beta blocker AV block Bradycardia Corneal microdeposits Elevation in transaminases Hepatotoxicity Hyperthyroidism Hypothyroidism Nausea QT prolongation Peripheral neuropathy Photosensitivity Pulmonary fibrosis Skin pigmentation (blue-gray) TdP Moderate* inhibitor of CYP2C9, weak† inhibitor of CYP2D6 Some inhibition of CYP3A Increases plasma concentrations of warfarin, lovastatin,‡ simvastatin,§ cyclosporine Inhibits p-gp Increases plasma concentrations of digoxin Dofetilide N/A CrCl >60 mL/ min: 500 μg twice daily CrCl 40-60 mL/min: 250 μg twice daily CrCl 20-40 mL/min: 125 μg twice daily CrCl <20 mL/ min: Contraindicated Kidney 10 h Inhibits IKr and augments late INa QT prolongation TdP Dofetilide is renally excreted via the renal cation transport system. These drugs inhibit renal cation transport, increase plasma dofetilide concentrations, and are contraindicated in patients taking dofetilide: Cimetidine Dolutegravir Ketoconazole Megestrol Prochlorperazine Trimethoprim (alone or in

combination with sulfamethoxazole) Verapamil In addition, hydrochlorothiazide (alone or in combination with triamterene) increases plasma dofetilide concentrations and should not be coadministered with dofetilide

Dronedarone N/A 400 mg twice daily Liver metabolism 13-19 h Inhibits IKr IKs, INa, IKur, Ito, ICa-L, IKAch Noncompetitive beta blocker Abdominal pain Asthenia Bradycardia Diarrhea Nausea and vomiting QT prolongation Rash TdP Dronedarone is a substrate for CYP3A and is a moderate inhibitor of CYP3A and CYP2D6 Dronedarone is also a substrate for, and inhibitor of, p-gp Dronedarone may increase plasma concentrations of: Dabigatran Digoxin Simvastatin‖ Sirolimus Tacrolimus Warfarin These drugs may increase plasma dronedarone concentrations: Grapefruit juice These drugs may decrease plasma dronedarone concentrations: CYP3A inducers including St. John’s wort, rifampin, and phenytoin

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