The following drugs have been described in case reports or relatively small series as potential antiarrhythmic drugs in Brugada syndrome patients. Although promising, the BrugadaDrugs.org Advisory Board stresses that the utmost care should be taken when using these drugs in the acute or chronic setting in Brugada syndrome patients. None of these drugs have proofed to completely prevent arrhythmias, some drugs have not been tested to an appreciable extent in Brugada syndrome patients and some drugs may have unacceptable side-effects. Preferably only (severely) symptomatic or otherwise high-risk patients in the absence of provoking drugs may be candidates for chronic therapeutic treatment in an experienced medical center. Currently, quinidine seems to be the treatment of choice for chronic therapy. Recently a prospective registry has started investigating the use of empiric quinidine therapy for asymptomatic Brugada syndrome patients: Viskin 2009 (to admit patients to this registry, please go to www.BrugadaSyndrome.info). Further, a study evaluating the number of appropriate ICD shocks in Brugada syndrome patients using quinidine vs. placebo has recently started (QUIDAM study).
As mentioned earlier, avoidance of provocative drugs/substances and timely treatment of fever is probably the most effective and safe treatment in many Brugada syndrome patients. However, some Brugada syndrome patients may (only) be appropriately treated with an implantable cardioverter defibrillator.
Acute treatment of arrhythmias has been described as follows:
Treatment of acute malignant arrhythmias / electrical storm has been commenced in 4 steps:
- Defibrillate/resuscitate if necessary
- Admit to specialized cardiac care unit / intensive care unit
- Stop / remove / treat provocative circumstances: 1) Treatment of fever by antipyretics and/or cooling together with treatment of fever origin; 2) Stop arrhythmogenic drugs/substances and/or treat arrhythmogenic drugs/substances overdose
- Therapeutic treatment with: 1) isoproterenol/isoprenaline (1 to 2 µg bolus i.v. followed by continuous infusion of 0.15-2.0 µg/min) and/or 2) quinidine (300 to 1500 mg /day). Aim at quinidine plasma levels of 1-3 µg/mL or 3.5-11 µmol/L. Please note that low dosages of quinidine in adults (i.e. ≤600mg per day) may be sufficient (Marquez et al.). Be aware that for children dosing is often tailored to bodyweight. In adults an isoproterenol regimen of 0.003±0.003 µg/kg/min has been used by Ohgo and 0.01 to 0.02 µg/kg/min has been used by Kasanuki. A quinidine dosage for children is 30–60 mg/kg/day given in 4 divided doses as used by Probst, and Suzuki.
- Please note that some patients (often children) with an SCN5A mutation may have a (‘use-dependant’) conduction phenotype as opposed to a Brugada phenotype. In the case of fever and the associated tachycardia, this combination may result in electric storms. Isoproterenol in these cases may actually have devastating effects because of the associated increment in heart rate, further slowing conduction and adding to the arrhythmogenic substrate. As opposed to isoproterenol, in these patients beta-blockers are indicated to slow down the heart rate. See Chockalingam 2011 and Chockalingam 2012.
- Advised references: Ohgo 2007, Watanabe 2006, Probst 2007, Marquez 2012.
Notes about the lists:
- On this list we summarized the drugs for which there is literature available on a possible antiarrhythmic effect in Brugada syndrome
- Drugs are listed with up to 3 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).
- 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 antiarrhythmic in Brugada syndrome patients.
- Class IIa:There is conflicting evidence and/or divergence of opinion about thedrug, but the weight of evidence/opinion is in favor of a potentially antiarrhythmic effect in Brugada syndrome patients.
- Class IIb: There is conflicting evidence and/or divergence of opinion about thedrug, and the potential antiarrhythmic 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 antiarrhythmic in Brugada syndrome patients
Please also read our Disclaimer.
Drugs with potential antiarrhythmic effect
(Alphabetical order generic name)
|Generic name||Brand name®||Class / Clinical use||References||Recommendation|
|Phosphodiesterase inhibitor||Tsuchiya 2002
|Beta-adrenergic receptor stimulation||Miyazaki 1996
|Beta-adrenergic receptor stimulation||Kyriazis 2009||Class IIa|
|Antiarrhythmic Agent||Suzuki 2000
Recommendation: Class I: convincing evidence/opinion; Class IIa: evidence/opinion less clear; Class IIb: conflicting evidence/opinion; Class III: very little evidence.
* Please read above the statement of caution indicated for patients with a loss-of-function SCN5A mutation who have a conduction phenotype instead of a Brugada phenotype (Treatment of acute malignant arrhythmias / electrical storm has been commenced in 4 steps).
Reports have postulated an antiarrhythmic effect of other drugs in Brugada syndrome. However, the BrugadaDrugs.org Advisory Board, considers the evidence on use of these drugs as antiarrhythmic treatment in Brugada syndrome patients to be too low (class III recommendation). These drugs are: amrinone (Marquez 2007), bepridil (Sugao 2005, Ohgo 2007, Chinushi 2011, Murakami 2010), clarithromycin (Marquez 2007), denopamine (Ohgo 2007), dimethyl lithospermate B (Fish 2006), disopyramide (Sumi 2010), mexiletine (Miyazaki 1996, Kasanuki 1997), milrinone (Marquez 2007), phentolamine (Miyazaki 1996), prazosin (Miyazaki 1996), sotalol (Bertaglia 1998, Glatter 2005), tedisamil (Marquez 2007, Perez Riera 2007 and 4-aminopyridine (Marquez 2007)
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.
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.