Description

Simple

A medication used to treat patients who are experiencing abnormal heart rhythms (atrial fibrillation).

Clinical

An antiarrhythmic medication used to treat patients with atrial fibrillation.

Overview

Vernakalant was developed by Cardiome Pharma as as an antiarrhythmic drug intended for rapid conversion of atrial fibrillation to sinus rhythm. It acts as an atypical class III antiarrhythmic drug that potentiates its effect in higher heart rates. Intravenous formulation was approved in Europe in September 2010 as Brinavess and in Canada in April 2017. It is an investigational drug under regulatory review by FDA.

Pharmacology

Indication

Indicated for the rapid conversion of recent onset of atrial fibrillation to sinus rhythm in adults for non-surgery patients that lasts for less than 7 days of duration and post-cardiac surgery patients with atrial fibrillation lasting less than 3 days of duration.

Pharmacodynamic

Vernakalant blocks currents in all phases of atrial action potential including atria-specific potassium currents (the ultra-rapid delayed rectifier and the acetylcholine dependent potassium currents) and prolongs the refractory period. It dose-dependently prolongs atrial refractoriness, prolongs AV... Read more

Mechanism of action

Vernakalant blocks atrial voltage-gated sodium channels in a dose and frequency-dependent manner and inhibits late sodium current (INa)which confers its effect on intra-atrial conduction. This current blockade enhance and onset of drug action accelerates in higher heart rate as the affinity of verna... Read more

Absorption

In patients, average peak plasma concentrations of vernakalant were 3.9 μg/ml following a single 10 minute infusion of 3 mg/kg vernakalant hydrochloride, and 4.3 μg/ml following a second infusion of 2 mg/kg with a 15 minute interval between doses [ Read more

Protein binding

Displays low protein binding and the free fraction of vernakalant in human serum is 53-63% at concentration range of 1-5 μg/ml.

Volume of distribution

Approximately 2L/kg.

Clearance

The typical total body clearance of vernakalant was estimated to be 0.41 l/hr/kg.

Half life

Elimination half life in CYP2D6 extensive metabolizers is 3 hours and 5.5 hours in poor metabolizers.

Route of elimination

Mainly eliminated via renal excretion.

Toxicity

Some common unwanted effects include hypotension, ventricular arrhythmias, bradycardia, atrial flutter, dysgeusia, paraesthesia, dizziness and nausea.

Adverse Effects

Contraindications

  • Lab Values:
    • systolic blood pressure <100mmHg
    • QT > 440 msec
  • Regions: Canada
  • Patient Conditions:
      • Name: NYHA Class III or IV heart failure
      • Drugbank Id: DBCOND0108430
  • Lab Values:
    • systolic blood pressure <100mmHg
    • QT > 440 msec
  • Regions: Canada
  • Patient Conditions:
      • Name: Severe Aortic Stenosis
      • Drugbank Id: DBCOND0046348
      • Modification Of:
        • Base:
          • Name: Aortic Stenosis
          • Drugbank Id: DBCOND0030894
        • Severity:
          • Includes:
            • severe
  • Lab Values:
    • systolic blood pressure <100mmHg
    • QT > 440 msec
  • Regions: Canada
  • Patient Conditions:
      • Name: Severe bradycardia
      • Drugbank Id: DBCOND0097899
      • Modification Of:
        • Base:
          • Name: Bradycardia
          • Drugbank Id: DBCOND0000504
        • Severity:
          • Includes:
            • severe
  • Lab Values:
    • systolic blood pressure <100mmHg
    • QT > 440 msec
  • Regions: Canada
  • Patient Conditions:
      • Name: Prolonged QT
      • Drugbank Id: DBCOND0099069
  • Lab Values:
    • systolic blood pressure <100mmHg
    • QT > 440 msec
  • Regions: Canada
  • Patient Conditions:
      • Name: Second or third degree atrioventricular heart block
      • Drugbank Id: DBCOND0108431
  • Lab Values:
    • systolic blood pressure <100mmHg
    • QT > 440 msec
  • Regions: Canada
  • Patient Conditions:
      • Name: Sinus Node Dysfunction
      • Drugbank Id: DBCOND0037740
  • Lab Values:
    • systolic blood pressure <100mmHg
    • QT > 440 msec
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute Decompensated Heart Failure
      • Drugbank Id: DBCOND0040566
      • Modification Of:
        • Base:
          • Name: Decompensated Heart Failure
          • Drugbank Id: DBCOND0035248
        • Severity:
          • Includes:
            • acute
  • Lab Values:
    • systolic blood pressure <100mmHg
    • QT > 440 msec
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute Coronary Syndrome
      • Drugbank Id: DBCOND0000545
      • Modification Of:
        • Base:
          • Name: Coronary Syndrome
          • Drugbank Id: DBCOND0040833
        • Severity:
          • Includes:
            • acute
  • Regions: Canada
  • With Categories Coadmin:
      • Name: Antiarrhythmic agents
      • Drugbank Id: DBCAT003297
      • Mesh Id: D000889

Food Interactions

    Information currently not available.

Interactions

Type in a drug name to check for interaction with Vernakalant
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Vernakalant can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Vernakalant.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Vernakalant.
Abatacept
The metabolism of Vernakalant can be increased when combined with Abatacept.
Abexinostat
The risk or severity of QTc prolongation can be increased when Vernakalant is combined with Abexinostat.
Abiraterone
The metabolism of Vernakalant can be decreased when combined with Abiraterone.
Acebutolol
Vernakalant may increase the arrhythmogenic activities of Acebutolol.
Aceprometazine
The risk or severity of QTc prolongation can be increased when Vernakalant is combined with Aceprometazine.
Acetaminophen
The metabolism of Acetaminophen can be decreased when combined with Vernakalant.
Acetyldigitoxin
Acetyldigitoxin may increase the arrhythmogenic activities of Vernakalant.
Acetyldigoxin
Vernakalant may increase the arrhythmogenic activities of Acetyldigoxin.
Acrivastine
The risk or severity of QTc prolongation can be increased when Vernakalant is combined with Acrivastine.
Adalimumab
The metabolism of Vernakalant can be increased when combined with Adalimumab.
Adenosine
Vernakalant may increase the arrhythmogenic activities of Adenosine.
Afelimomab
The metabolism of Vernakalant can be increased when combined with Afelimomab.
Agmatine
Vernakalant may increase the arrhythmogenic activities of Agmatine.
Ajmaline
Ajmaline may increase the arrhythmogenic activities of Vernakalant.
Alfuzosin
The risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Vernakalant.
Alimemazine
The risk or severity of QTc prolongation can be increased when Alimemazine is combined with Vernakalant.
Almotriptan
The metabolism of Almotriptan can be decreased when combined with Vernakalant.
8 References
  1. 1 . Naccarelli GV, Wolbrette DL, Samii S, Banchs JE, Penny-Peterson E, Stevenson R, Gonzalez MD: Vernakalant--a promising therapy for conversion of recent-onset atrial fibrillation. Expert Opin Investig Drugs. 2008 May;17(5):805-10. doi: 10.1517/13543784.17.5.805 .PubMed: 18447605
  2. 2 . Cheng JW: Vernakalant in the management of atrial fibrillation. Ann Pharmacother. 2008 Apr;42(4):533-42. doi: 10.1345/aph.1K542. Epub 2008 Mar 11.PubMed: 18334607
  3. 3 . Dorian P, Pinter A, Mangat I, Korley V, Cvitkovic SS, Beatch GN: The effect of vernakalant (RSD1235), an investigational antiarrhythmic agent, on atrial electrophysiology in humans. J Cardiovasc Pharmacol. 2007 Jul;50(1):35-40.PubMed: 17666913
  4. 4 . Orth PM, Hesketh JC, Mak CK, Yang Y, Lin S, Beatch GN, Ezrin AM, Fedida D: RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents. Cardiovasc Res. 2006 Jun 1;70(3):486-96. Epub 2006 Feb 14.PubMed: 16545351
  5. 5 . Savelieva I, Graydon R, Camm AJ: Pharmacological cardioversion of atrial fibrillation with vernakalant: evidence in support of the ESC Guidelines. Europace. 2014 Feb;16(2):162-73. doi: 10.1093/europace/eut274. Epub 2013 Oct 9.PubMed: 24108230
  6. 6 . Camm AJ: The vernakalant story: how did it come to approval in Europe and what is the delay in the U.S.A? Curr Cardiol Rev. 2014 Nov;10(4):309-14.PubMed: 24821654
  7. 7 . Tsuji Y, Dobrev D: Safety and efficacy of vernakalant for acute cardioversion of atrial fibrillation: an update. Vasc Health Risk Manag. 2013;9:165-75. doi: 10.2147/VHRM.S43720. Epub 2013 Apr 23.PubMed: 23637539
  8. 8 . European Medicines Agency Summary of product characteristics Link