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Pharmacokinetic drug interactions frequently involve the inhibition of key metabolic pathways, resulting in accumulation of a substrate drug. Additionally, over the past 2 decades, the P-gp (permeability glycoprotein) has been increasingly cited as a significant source of drug interactions. Pharmacodynamic drug interactions involving AADs commonly involve additive QT prolongation. Amiodarone, quinidine, and dofetilide are AADs with numerous and clinically significant drug interactions. Recent studies have also demonstrated increased morbidity and mortality with the use of digoxin and other AAD which interact with P-gp. QT prolongation is an important pharmacodynamic interaction involving mainly Vaughan-Williams class III AAD as many commonly used drug classes, such as macrolide antibiotics, fluoroquinolone antibiotics, antipsychotics, and antiemetics prolong the QT interval. Whenever possible, serious drug-drug interactions involving AAD should be avoided. If unavoidable, patients will require closer monitoring and the concomitant use of interacting agents should be minimized. Increasing awareness of drug interactions among clinicians will significantly improve patient safety for patients with arrhythmias.<\/jats:p>","DOI":"10.1161\/circep.121.007955","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T09:00:57Z","timestamp":1651482057000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Drug Interactions Affecting Antiarrhythmic Drug Use"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3576-0435","authenticated-orcid":true,"given":"Philip L.","family":"Mar","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiology, St. Louis University, St. Louis, MO (P.L.M., P.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8375-8535","authenticated-orcid":true,"given":"Piotr","family":"Horbal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, St. Louis University, St. Louis, MO (P.L.M., P.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7835-6045","authenticated-orcid":true,"given":"Mina K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Heart, Vascular &amp; Thoracic Institute (M.K.C.), Cleveland Clinic, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan W.","family":"Dukes","sequence":"additional","affiliation":[{"name":"Community Memorial Hospital, Ventura, CA (J.W.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3623-2252","authenticated-orcid":true,"given":"Michael","family":"Ezekowitz","sequence":"additional","affiliation":[{"name":"Lankenau Heart Institute, Bryn Mawr Hospital &amp; Sidney Kimmel Medical College (M.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1492-2693","authenticated-orcid":true,"given":"Dhanunjaya","family":"Lakkireddy","sequence":"additional","affiliation":[{"name":"Kansas City Heart Rhythm Institute, KS (D.L., R.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-1626","authenticated-orcid":true,"given":"Gregory Y.H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science, University of Liverpool &amp; Liverpool Heart &amp; Chest Hospital, Liverpool, United Kingdom (G.Y.H.L.)."},{"name":"Department of Clinical Medicine, Aalborg, Denmark (G.Y.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-1669","authenticated-orcid":true,"given":"Mike","family":"Miletello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (M.M.), Cleveland Clinic, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4308-0456","authenticated-orcid":true,"given":"Peter A.","family":"Noseworthy","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (P.A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-1866","authenticated-orcid":true,"given":"James A.","family":"Reiffel","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2117-9463","authenticated-orcid":true,"given":"James E.","family":"Tisdale","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Purdue University (J.E.T.)."},{"name":"School of Medicine, Indiana University, Indianapolis (J.E.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-045X","authenticated-orcid":true,"given":"Brian","family":"Olshansky","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Iowa, Iowa City (B.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-3687","authenticated-orcid":true,"given":"Rakesh","family":"Gopinathannair","sequence":"additional","affiliation":[{"name":"Kansas City Heart Rhythm Institute, KS (D.L., R.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"from the American Heart Association Electrocardiography and Arrhythmias Committee of the Council of Clinical Cardiology","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","volume-title":"Corvert. 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