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
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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.