The following drugs have been associated with the typical (type-1) Brugada syndrome ECG. However, there is (yet) no substantial evidence that these drugs can, in addition to the ECG phenotype, also cause malignant arrhythmias. Furthermore, we listed drugs for which there is only experimental evidence (in-vivo or in-vitro) that suggests a possible deleterious effect in Brugada syndrome. However, as mentioned earlier this deleterious effect has not been documented clearly and some patients may benefit from these drugs for other reasons. Nevertheless, it should be considered to advice patients with Brugada syndrome to avoid these drugs or to use these drugs only after extensive consideration and/or in controlled conditions.

Notes about the lists:

• On this list we summarized those drugs for which there is a possible association noted in the literature between the drug and the Brugada syndrome.
• Drugs are listed with up to 3 common brand names. There may be over 100 different brand names for different drugs, an effort to list those we know of you can find here. It is also important to look at the active drugs in medicines that contain a combination of drugs.
• Lists contain links to DrugBank or PubChem (click on the drug name) and also (several) PubMed links to articles on the association between the drug and Brugada syndrome (click on the reference).
• We advice our Brugada syndrome patients to give this letter to all of their health care providers.
• Please cite this site as: Postema PG, Wolpert C, Amin AS, Probst V, Borggrefe M, Roden DM, Priori SG, Tan HL, Hiraoka M, Brugada J, Wilde AA. Drugs and Brugada syndrome patients: review of the literature, recommendations and an up-to-date website (www.brugadadrugs.org). Heart Rhythm 2009;6(9):1335-1341. (Free available from Heart Rhythm, PubMed link here).
• Lists contain a classifying column ‘Recommendation’ in which the available evidence from the literature and the expert opinion of the BrugadaDrugs.org Advisory Boardis described. Please note that there are no randomized clinical studies in Brugada syndrome patients, therefore the level of evidence is mostly C (only consensus opinion of experts, case studies, or standard-of-care) and for some B (non-randomized studies).
  • Class I: There is evidence and/or general agreement that a given drug is potentially arrhythmic in Brugada syndrome patients.
  • Class IIa:There is conflicting evidence and/or divergence of opinion about the
    drug, but the weight of evidence/opinion is in favor of a potentially arrhythmic effect in Brugada syndrome patients.
  • Class IIb: There is conflicting evidence and/or divergence of opinion about the
    drug, and the potential arrhythmic effect in Brugada syndrome patients is less well established by evidence/opinion.
  • Class III: There is no or very little evidence and/or general agreement that a drug is potentially arrhythmic in Brugada syndrome patients

Please also read our Disclaimer.

Antiarrhythmic drugs

(Alphabetical order generic name)

Generic name	Brand name®	Class / Clinical use	References	Recommendation
Amiodarone	e.g. Cordarone® - more brand names here -	Antiarrhythmic Agent (3 – also 1A, 2, and 4 effects) / Arrhythmias	Chalvidan 2000 Paul 2006 D’Aloia 2012 Wu 2008	Class IIb
Cibenzoline	e.g. Cipralan® - more brand names here -	Antiarrhythmic Agent (1A: Na-blocker) / Arrhythmias	Tada 2000 Sarkozy 2005 Niwa 1998	Class IIb
Disopyramide†	e.g. Dicorantil® Norpace® Ritmoforine® - more brand names here -	Antiarrhythmic Agent (1A: Na-blocker) / Arrhythmias	Miyazaki 1996 Chinushi 1997 Shimizu 2000 Sugao 2005 Sumi 2010 Grant 2000	Class IIb
Lidocaine*	e.g. Xylocaine® - more brand names here -	Antiarrhythmic Agent (1A: Na-blocker) / Arrhythmias	Miyazaki 1996 Barajas 2008	Class IIb
Propranolol	e.g. Inderal® - more brand names here -	Antiarrhythmic Agent (2: B-blocker) / Arrhythmias	Miyazaki 1996 Shimada 1996 Kasanuki 1997 Nademanee 2003 Aouate 2005 Shimada 1999	Class IIb
Verapamil	e.g. Covera® Isoptin® - more brand names here -	Antiarrhythmic Agent (4: Ca-blocker) / Arrhythmias	Miyazaki 1996 Chinushi 2006 Fish 2008	Class IIb

Recommendation: Class I: convincing evidence/opinion; Class IIa: evidence/opinion less clear; Class IIb: conflicting evidence/opinion; Class III: very little evidence.
† Disopyramide has been either suggested to be pro-arrhythmic or anti-arrhythmic in Brugada syndrome patients. The reason for these contradictory results is currently uncertain but could possibly include disparate underlying genetic defects. The Brugadadrugs.org Advisory Board advices caution and rigorous monitoring when using this drug to be able to react promptly to possible untoward effects.
* Lidocaine use for local anesthesia (e.g. by dentists) does seem to be safe when combined with adrenaline/epinephrine (e.g. xylocaine dental/epinephrine or articaïne/epinefrine (Ultracain® or Septanest®) 1:100,000) and the amount administrated is low as it results in a local effect only (Theodotou 2009). When applied on the skin it is also unlikely that there will be systemic effects, and will most probably be safe.

Psychotropic drugs

(Alphabetical order generic name)

Generic name	Brand name®	Class / Clinical use	References	Recommendation
Carbamazepine*	e.g. Carbatrol® Tegretol® - more brand names here -	Anticonvulsant Agent	Megarbane 2006 Bräu 2001	Class IIb
Cyamemazine	e.g. Cianatil® - more brand names here -	Antidepressive Agent, Phenothiazine	Rouleau 2001 Crumb 2006	Class IIb
Dosulepine	e.g. Prothiaden® - more brand names here -	Antidepressive Agent, Tricyclic	Meert 2009	Class IIb
Doxepin	e.g. Sinequan® Triadapin® Zonalon® - more brand names here -	Antidepressive Agent, Tricyclic	Bebarta 2007 Muir 1982	Class IIb
Fluoxetine	e.g. Prozac® Sarafem® - more brand names here -	Antidepressive Agent, SSRI	Rouleau 2001 Pacher 2000	Class IIb
Fluvoxamine	e.g. Fevarin® Luvox® - more brand names here -	Antidepressive Agent, SSRI	Stirnimann 2009	Class IIb
Imipramine	e.g. Declomipramine® Norfranil® Tofranil® - more brand names here -	Antidepressive Agent, Tricyclic	Robert 1996	Class IIb
Maprotiline	e.g. Deprilept® - more brand names here -	Antidepressive Agent, Tetracyclic	Bolognesi 1997 Igawa 1988	Class IIb
Paroxetine	e.g. Paxil® Seroxat® - more brand names here -	Antidepressive Agent, SSRI	Sawhney 2009 Wang 2008 Yokota 1987	Class IIb
Perphenazine	e.g. Perphenan® - more brand names here -	Antidepressive Agent, Phenothiazine	Bolognesi 1997 Bébarová 2009	Class IIb
Phenytoin	e.g. Dilantin® Diphantoine® Epanutin® - more brand names here -	Anticonvulsant and Antiarrhythmic Agent	Al Aloul 2007 Xu 1991	Class IIb
Thioridazine	e.g. Mellaril® Ridazine® - more brand names here -	Antipsychotic Agent	Copetti 2005	Class IIb

Recommendation: Class I: convincing evidence/opinion; Class IIa: evidence/opinion less clear; Class IIb: conflicting evidence/opinion; Class III: very little evidence.

*Carbamazepine is structurally closely related to Oxcarbazepine which is on the avoid list.

Anesthetics / analgesics

(Alphabetical order generic name)

Generic name	Brand name®	Class / Clinical use	References	Recommendation
Ketamine	e.g. Esketamine® Ketanest® - more brand names here -	Anesthetic Agent	Rollin 2011 Hara 1998	Class IIb
Tramadol	e.g. Ryzolt® Tramal® Zydol® - more brand names here -	Narcotic analgesic	Cole 2010 Haeseler 2006	Class IIb

Recommendation: Class I: convincing evidence/opinion; Class IIa: evidence/opinion less clear; Class IIb: conflicting evidence/opinion; Class III: very little evidence.

Other substances

(Alphabetical order generic name)

Generic name	Brand name®	Class / Clinical use	References	Recommendation
Dimenhydrinate	e.g. Permital® - more brand names here -	Antiemetic Agent/ Histamine H1 antagonist	Pastor 2001 Kuo 2000	Class IIb
Diphenhydramine	e.g. Benadryl® Dimedrol® - more brand names here -	Histamine H1 antagonist	Lopez 2005 Kuo 2000	Class IIb
Edrophonium	e.g. Enlon® Tensilon® - more brand names here -	Cholinergic Agent	Miyazaki 1996 Kasanuki 1997	Class IIb
Indapamide	e.g. Idapamide® Lozol® - more brand names here -	Diuretic Agent/Hypertension	Mok 2008	Class IIb
Metoclopramide	e.g. Primperan® Reglan® - more brand names here -	Antiemetic Agent/dopamine antagonist	Bonilla 2011 Wu 1992	Class IIb
Terfenadine/ Fexofenadine	e.g. Seldane® Teldane® Allegra® - more brand names here -	Antihistamine	Matsuki 2009 DiDiego 2002	Class IIb

Recommendation: Class I: convincing evidence/opinion; Class IIa: evidence/opinion less clear; Class IIb: conflicting evidence/opinion; Class III: very little evidence..

Disclaimer and Waiver
The information presented is intended solely for the purpose of providing general information about health related matters. We do our best to ascertain that all information on this site is correct and up-to-date. However, we cannot guarantee that it is. The information provided here is for educational and informational purposes only and designed primarily for use by qualified physicians and other medical professionals. It is not intended for any other purpose, including, but not limited to, medical or pharmaceutical advice and/or treatment, nor is it intended to substitute for the users’ relationships with their own health care/pharmaceutical providers. To that extent, by continued use of this program, the user affirms the understanding of the purpose and releases the Academic Medical Center, the BrugadaDrugs.org Advisory Board and Cardionetworks from any claims arising out of his/her use of the website.

Principal limitation
It should be clear to the users of this site that the principal limitation of the association between certain drugs, Brugada syndrome and arrhythmias, is that there are quite often only (a number of) case reports and experimental studies suggesting an effect in Brugada syndrome. Further, there may conflicting results and there may be large variability for Brugada syndrome patients in their response to certain drugs. This response may also differ in different conditions (e.g. with or without fever, drug in therapeutic range, overdosed or in combination with other drugs etc.). Clinical decision making should be based on more than the presence or absence of a (single) association in another patient.