Drugs preferably avoided by Brugada syndrome patients

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 also 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 advise 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 advise our Brugada syndrome patients to give this letter to all of their health care providers.
  • 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
  • For information on the treatment of co-morbidities in Brugada syndrome patients several papers are available, e.g. Postema et al. 2013 (free PMC article).

Please also read our Disclaimer.

Antiarrhythmic drugs

Generic nameBrand name®Clinical useReferencesClass
Amiodaronee.g.
Cordarone®
-other names-
Antiarrhythmic Agent
(class 3 - also 1A, 2, and 4 effects) /
Arrhythmias
Chalvidan 2000
Paul 2006
D'Aloia 2012
Wu 2008
IIb
Cibenzolinee.g.
Cipralan®
-other names-
Antiarrhythmic Agent
(class 1A: Na-blocker) /
Arrhythmias
Tada 2000
Sarkozy 2005
Niwa 1998
IIb
Disopyramidee.g.
Dicorantil®
Norpace®
Ritmoforine®
-other names-
Antiarrhythmic Agent
(class 1A: Na-blocker) /
Arrhythmias
Miyazaki 1996
Chinushi 1997
Shimizu 2000
Sugao 2005
Sumi 2010
Belhassen 2015
Grant 2000
IIb
Lidocaine*e.g.
Xylocaine®
-other names-
Antiarrhythmic Agent
(class 1A: Na-blocker) /
Arrhythmias
Miyazaki 1996
Barajas 2008
IIb
Propranolol#e.g.
Inderal®
-other names-
Antiarrhythmic Agent
(class 2: B-blocker) /
Arrhythmias
Miyazaki 1996
Shimada 1996
Kasanuki 1997
Nademanee 2003
Aouate 2005
Shimada 1999
IIb
Verapamile.g.
Covera®
Isoptin®
-other names-
Antiarrhythmic Agent
(class 4: Ca-blocker) /
Arrhythmias
Miyazaki 1996
Chinushi 2006
Yakut 2017
Fish 2008
IIb
Vernakalante.g.
Brinavess®
Kynapid®
-other names-
Antiarrhythmic Agent
(class 1 and 3)
Zografos 2014
Wettwer 2013
IIb

Recommendation class: 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). Also in a controlled setting such as during ICD (implantable cardioverter defibrillator) implantation there have been no descriptions of untoward events although the amount lidocaine administered can be substantial, still the utmost care should be taken to avoid systemic injection. When applied on the skin (e.g. for children requiring venapuncture or vaccination) it is also extremely unlikely that there will be systemic effects, and this will thus most probably also be safe to do.
# Use of propranolol, or rather betablockers in general, can be suitable when anti-bradycardia therapy is ensured by a pacemaker or implantable cardioverter defibrillator. Moreover, especially in the situation of a use-dependant conduction disease phenotype (see also Emergencies) betablockers are even first choice therapy to lower heart rate and decrease arrhythmic risk.

Psychotropic drugs

Generic nameBrand name®Clinical useReferencesClass
Bupropione.g.
Amfebutamone®
Aplenzin®
Wellbutrin®
-other names-
Antidepressive Agent,
unicyclic
Alampay 2014
Caillier 2012
IIb
Carbamazepine*e.g.
Carbatrol®
Tegretol®
-other names-
Anticonvulsant AgentMegarbane 2006
Bräu 2001
IIb
Clothiapine**e.g.
Clotiapine®
Entumin®
-other names-
Antipsychotic AgentAdler 2013IIb
Cyamemazinee.g.
Cianatil®
-other names-
Antidepressive Agent,
Phenothiazine
Rouleau 2001
Crumb 2006
IIb
Dosulepinee.g.
Dothiepin®
Prothiaden®
-other names-
Antidepressive Agent,
Tricyclic
Meert 2010
Kiran 2010
IIb
Doxepine.g.
Sinequan®
Triadapin®
Zonalon®
-other names-
Antidepressive Agent,
Tricyclic
Bebarta 2007
Muir 1982
IIb
Fluoxetinee.g.
Prozac®
Sarafem®
-other names-
Antidepressive Agent,
SSRI
Rouleau 2001
Pacher 2000
Poulin 2014
IIb
Fluvoxaminee.g.
Fevarin®
Luvox®
-other names-
Antidepressive Agent,
SSRI
Stirnimann 2009IIb
Imipraminee.g.
Declomipramine®
Norfranil®
Tofranil®
-other names-
Antidepressive Agent,
Tricyclic
Robert 1996IIb
Lamotriginee.g.
Lamictal®
-other names-
Anti-epileptic Agent,
Bi-polar and
depressive disorders
Chandra 2009
Strimel 2010
Rodriques 2013
Lang 1993
IIb
Maprotilinee.g.
Deprilept®
-other names-
Antidepressive Agent,
Tetracyclic
Bolognesi 1997
Igawa 1988
IIb
Paroxetinee.g.
Paxil®
Seroxat®
-other names-
Antidepressive Agent,
SSRI
Sawhney 2009
Wang 2008
Yokota 1987
IIb
Perphenazinee.g.
Perphenan®
-other names-
Antidepressive Agent,
Phenothiazine
Bolognesi 1997
Bébarová 2009
IIb
Phenytoine.g.
Dilantin®
Diphantoine®
Epanutin®
-other names-
Anticonvulsant,
Antiarrhythmic Agent
Al Aloul 2007
Swe 2016
Xu 1991
IIb
Thioridazinee.g.
Mellaril®
Ridazine®
-other names-
Antipsychotic AgentCopetti 2005IIb

Recommendation class: 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.
**Clothiapine is structurally closely related to Loxapine which is on the avoid list.

Anesthetics / analgesics

Generic nameBrand name®Clinical useReferencesClass
Ketaminee.g.
Esketamine®
Ketanest®
-other names-
Anesthetic AgentRollin 2011
Hara 1998
IIb
Tramadole.g.
Ryzolt®
Tramal®
Zydol®
-other names-
Narcotic analgesicCole 2010
Haeseler 2006
IIb

Recommendation class: Class I: convincing evidence/opinion; Class IIa: evidence/opinion less clear; Class IIb: conflicting evidence/opinion; Class III: very little evidence.
For more information on anesthetic management of Brugada syndrome patients; a review article has been written by Kloesel & Ackerman, when appropriate precautions are taken (general) anesthesia can be performed safely.

Other substances

Generic nameBrand name®Clinical useReferencesClass
Dimenhydrinatee.g.
Permital®
-other names-
Antiemetic Agent /
Histamine H1 antagonist
Pastor 2001
Kuo 2000
IIb
Diphenhydraminee.g.
Benadryl®
Dimedrol®
-other names-
Histamine H1 antagonistLopez 2005
Kuo 2000
IIb
Edrophoniume.g.
Enlon®
Tensilon®
-other names-
Cholinergic AgentMiyazaki 1996
Kasanuki 1997
IIb
Indapamidee.g.
Idapamide®
Lozol®
-other names-
Diuretic Agent/HypertensionMok 2008IIb
Metoclopramidee.g.
Primperan®
Reglan®
-other names-
Antiemetic Agent /
dopamine antagonist
Bonilla 2011
Wu 1992
IIb
Terfenadine/
Fexofenadine
e.g.
Seldane®
Teldane®
Allegra®
-other names-
AntihistamineMatsuki 2009
DiDiego 2002
IIb

Recommendation class: 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.