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 name | Brand name® | Clinical use | References | Class |
|---|---|---|---|---|
| Amiodarone | e.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 |
| Cibenzoline | e.g. Cipralan® -other names- | Antiarrhythmic Agent (class 1A: Na-blocker) / Arrhythmias | Tada 2000 Sarkozy 2005 Niwa 1998 | IIb |
| Disopyramide† | e.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 |
| Verapamil | e.g. Covera® Isoptin® -other names- | Antiarrhythmic Agent (class 4: Ca-blocker) / Arrhythmias | Miyazaki 1996 Chinushi 2006 Yakut 2017 Fish 2008 | IIb |
| Vernakalant | e.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 name | Brand name® | Clinical use | References | Class |
|---|---|---|---|---|
| Bupropion | e.g. Amfebutamone® Aplenzin® Wellbutrin® -other names- | Antidepressive Agent, unicyclic | Alampay 2014 Caillier 2012 | IIb |
| Carbamazepine* | e.g. Carbatrol® Tegretol® -other names- | Anticonvulsant Agent | Megarbane 2006 Ota 2018 Bräu 2001 | IIb |
| Clothiapine** | e.g. Clotiapine® Entumin® -other names- | Antipsychotic Agent | Adler 2013 | IIb |
| Cyamemazine | e.g. Cianatil® -other names- | Antidepressive Agent, Phenothiazine | Rouleau 2001 Crumb 2006 | IIb |
| Dosulepine | e.g. Dothiepin® Prothiaden® -other names- | Antidepressive Agent, Tricyclic | Meert 2010 Kiran 2010 | IIb |
| Doxepin | e.g. Sinequan® Triadapin® Zonalon® -other names- | Antidepressive Agent, Tricyclic | Bebarta 2007 Muir 1982 | IIb |
| Fluoxetine | e.g. Prozac® Sarafem® -other names- | Antidepressive Agent, SSRI | Rouleau 2001 Pacher 2000 Poulin 2014 | IIb |
| Fluvoxamine | e.g. Fevarin® Luvox® -other names- | Antidepressive Agent, SSRI | Stirnimann 2009 | IIb |
| Imipramine | e.g. Declomipramine® Norfranil® Tofranil® -other names- | Antidepressive Agent, Tricyclic | Robert 1996 | IIb |
| Lamotrigine | e.g. Lamictal® -other names- | Anti-epileptic Agent, Bi-polar and depressive disorders | Chandra 2009 Strimel 2010 Rodriques 2013 Banfi 2020 Lang 1993 | IIb |
| Maprotiline | e.g. Deprilept® -other names- | Antidepressive Agent, Tetracyclic | Bolognesi 1997 Igawa 1988 | IIb |
| Paroxetine | e.g. Paxil® Seroxat® -other names- | Antidepressive Agent, SSRI | Sawhney 2009 Wang 2008 Yokota 1987 | IIb |
| Perphenazine | e.g. Perphenan® -other names- | Antidepressive Agent, Phenothiazine | Bolognesi 1997 Bébarová 2009 | IIb |
| Phenytoin | e.g. Dilantin® Diphantoine® Epanutin® -other names- | Anticonvulsant, Antiarrhythmic Agent | Al Aloul 2007 Swe 2016 Xu 1991 | IIb |
| Thioridazine | e.g. Mellaril® Ridazine® -other names- | Antipsychotic Agent | Copetti 2005 | IIb |
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 name | Brand name® | Clinical use | References | Class |
|---|---|---|---|---|
| Ketamine | e.g. Esketamine® Ketanest® -other names- | Anesthetic Agent | Rollin 2011 Hara 1998 | IIb |
| Tramadol | e.g. Ryzolt® Tramal® Zydol® -other names- | Narcotic analgesic | Cole 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 name | Brand name® | Clinical use | References | Class |
|---|---|---|---|---|
| Dimenhydrinate | e.g. Permital® -other names- | Antiemetic Agent / Histamine H1 antagonist | Pastor 2001 Kuo 2000 | IIb |
| Diphenhydramine | e.g. Benadryl® Dimedrol® -other names- | Histamine H1 antagonist | Lopez 2005 Kuo 2000 | IIb |
| Edrophonium | e.g. Enlon® Tensilon® -other names- | Cholinergic Agent | Miyazaki 1996 Kasanuki 1997 | IIb |
| Indapamide | e.g. Idapamide® Lozol® -other names- | Diuretic Agent/Hypertension | Mok 2008 | IIb |
| Metoclopramide | e.g. Primperan® Reglan® -other names- | Antiemetic Agent / dopamine antagonist | Bonilla 2011 Wu 1992 | IIb |
| Terfenadine/ Fexofenadine | e.g. Seldane® Teldane® Allegra® -other names- | Antihistamine | Matsuki 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.