BrugadaDrugs.org

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 listed drugs for which there is only experimental evidence (in-vivo or in-vitro) that suggests a possible deleterious effect in Brugada syndrome. 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 4 common brand names. There are several brand names for many of the drugs, which are not all listed. 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 Board is 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®	Antiarrhythmic Agent (3 – also 1A, 2, and 4 effects) / Arrhythmias	Chalvidan et al. 2000 Paul et al. 2006 Wu et al. 2008	Class IIb
Cibenzoline	e.g. Cipralan®	Antiarrhythmic Agent (1A: Na-blocker) / Arrhythmias	Tada et al. 2000 Sarkozy et al. 2005 Niwa et al. 1998	Class IIb
Disopyramide	e.g. Dicorantil® Norpace® Ritmoforine®	Antiarrhythmic Agent (1A: Na-blocker) / Arrhythmias	Miyazaki et al. 1996 Chinushi et al. 1997 Shimizu et al. 2000 Sugao et al. 2005 Sumi et al. 2009 Grant et al. 2000	Class IIb
Lidocaine*	e.g. Xylocaine®	Antiarrhythmic Agent (1A: Na-blocker) / Arrhythmias	Miyazaki et al. 1996 Barajas et al. 2008	Class IIb
Propranolol	e.g. Inderal®	Antiarrhythmic Agent (2: B-blocker) / Arrhythmias	Miyazaki et al. 1996 Shimada et al. 1996 Kasanuki et al. 1997 Aouate et al. 2005 Shimada et al. 1999	Class IIb
Verapamil	e.g. Calan® Covera® Isoptin® Verelan®	Antiarrhythmic Agent (4: Ca-blocker) / Arrhythmias	Miyazaki et al. 1996 Chinushi et al. 2006 Fish et al. 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.
* 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®) 1:100000) and the amount administrated is low as it results in a local effect only.

Psychotropic drugs

(Alphabetical order generic name)

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

Anesthetics

(Alphabetical order generic name)

Generic name	Brand name®	Class / Clinical use	References	Recommendation
Ketamine	e.g. Esketamine® Ketanest®	Anesthetic Agent	Rollin et al. 2010 Hara et al. 1998	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®	Antiemetic Agent/ Histamine H1 antagonist	Pastor et al. 2001 Kuo et al. 2000	Class IIb
Diphenhydramine	e.g. Benadryl® Dimedrol®	Histamine H1 antagonist	Lopez et al. 2005 Kuo et al. 2000	Class IIb
Edrophonium	e.g. Enlon® Tensilon®	Cholinergic Agent	Miyazaki et al. 1996 Kasanuki et al. 1997	Class IIb
Indapamide	e.g. Idapamide® Lozol®	Diuretic Agent/Hypertension	Mok et al. 2008	Class IIb
Terfenadine/ Fexofenadine	e.g. Seldane® Teldane® Allegra®	Antihistamine	Matsuki et al. 2009 DiDiego et al. 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..

Antianginal drugs

(Alphabetical order generic name)

Generic name	Brand name®	Class / Clinical use	References	Recommendation
Diltiazem	e.g. Tildiem®	Vasodilator Agent (Ca-blocker) / Hypertension, vasospasms	Itoh et al. 1999 Sasaki et al. 2006 Antzelevitch et al. 2005 Miyazaki et al. 1996	Class III
Nicorandil	e.g. Ikorel®	Vasodilator Agent (K-agonist / NO-donor) / Angina pectoris	Antzelevitch et al. 2005 Robert et al. 1999	Class III
Nifedipine	e.g. Adalat®	Vasodilator Agent (Ca-blocker) / Angina pectoris, hypertension	Antzelevitch et al. 2005 Hussain et al. 1997	Class III
Nitroglycerine	e.g. Nitrospan® Tridil®	Vasodilator Agent (NO donor) / Angina pectoris	Matsuo et al. 1998 Antzelevitch et al. 2005 Korth. 1975	Class III
Sorbidnitrate	e.g. Cedocard® Isordil®	Vasodilator Agent (NO donor) / Angina pectoris	Chinushi et al. 2006 Antzelevitch et al. 2005 Atanassova et al. 1992	Class III

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.