Vernakalant
- Atc Codes:C01BG11
- CAS Codes:748810-28-8
- PHARMGKB ID:748810-28-8
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Caution and personalized dose adjustment in patients with the following genotypes
- Other genes that may be involved
- Substrate of
- Drug Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
Europe
Czech Republic: Brinavess; Dermark: Brinavess; Estonia: Brinavess; Finland: Brinavess; Germany: Brinavess; Greece: Brinavess; Hungary: Brinavess; Ireland: Brinavess; Latvia: Brinavess; Lithuania: Brinavess; Luxembourg: Brinavess; Malta: Brinavess; Netherlands: Brinavess; Poland: Brinavess; Portugal: Brinavess; Romania: Brinavess; Slovakia: Brinavess; Slovenia: Brinavess; Spain: Brinavess; Sweden: Brinavess.
Drug combinations
Chemistry
Vernakalant Hydrochloride: C~20~H~31~NO~4~ HCl. Mw: 385.20. (3R)-1-[(1R,2R)-2-[2-(3,4-dimethoxyphenyl)ethoxy]cyclohexyl]pyrrolidin-3-ol hydrochloride. CAS-748810-28-8.
Pharmacologic Category
Antiarrhythmics, Miscellaneous. Other Antiarrhythmics class I and III. (ATC-Code: C01BG11).
Mechanism of action
Vernakalant is an antiarrhythmic medicine that acts preferentially in the atria to prolong atrial refractoriness and to rate-dependently slow impulse conduction. These anti-fibrillatory actions on refractoriness and conduction are thought to suppress re-entry, and are potentiated in the atria during atrial fibrillation. The relative selectivity of vernakalant on atrial vs ventricular refractoriness is postulated to result from the block of currents that are expressed in the atria, but not in the ventricles, as well as the unique electrophysiologic condition of the fibrillating atria. However, blockade of cationic currents, including hERG channels and cardiac voltage-dependent sodium channels present in the ventricles, has been documented.
Therapeutic use
Rapid conversion of recent onset atrial fibrillation to sinus rhythm in adults (for non-surgery patients, atrial fibrillation ≤7 days duration; and for post-cardiac surgery patients, atrial fibrillation ≤3 days duration).
Pregnancy and lactiation implications
It is preferable to avoid the use of vernakalant during pregnancy. Caution should be exercised when used in breastfeeding women.
Unlabeled use
Contraindications
Hypersensitivity to the active substance or to any of the excipients. Patients with severe aortic stenosis, patients with systolic blood pressure <100 mm Hg, and patients with heart failure class NYHA III and NYHA IV. Patients with prolonged QT at baseline (uncorrected >440 ms), or severe bradycardia, sinus node dysfunction or second-degree and third-degree heart block in the absence of a pacemaker. Use of intravenous rhythm control anti-arrhythmics (class I and class III) within 4 hours prior to vernakalant administration. Acute coronary syndrome (including myocardial infarction) within the last 30 days.
Warnings and precautions
Patients should be observed with assessment of vital signs and continuous cardiac rhythm monitoring during and after administration of treatment, until clinical and ECG parameters have stabilized. Prior to attempting pharmacological cardioversion, ensure that patients are adequately hydrated and hemodynamically optimized and if necessary, patients should be anticoagulated in accordance with treatment guidelines. In patients with uncorrected hypokalemia (serum potassium of less than 3.5 mmol/L), potassium levels should be corrected prior to use. During infusion, if patients develop clinically meaningful bradycardia and/or hypotension or develop ECG changes (such as a clinically meaningful sinus pause, complete heart block, new bundle branch block, significant prolongation of the QRS or QT interval, changes consistent with ischemia or infarction and ventricular arrhythmia), the administration of vernakalant should be discontinued and these patients should receive appropriate medical management. If these events occur during the first infusion, patients should not receive the second dose. Hypotension can occur in a small number of patients (patients with congestive heart failure (CHF) have higher risk for hypotension and ventricular arrhythmia (vernakalant should be used cautiously in hemodynamically stable patients with CHF functional classes NYHA I to II, and is contraindicated in CHF patients corresponding to NYHA III or NYHA IV). Vernakalant was not found to be effective in converting typical primary atrial flutter to sinus rhythm (if atrial flutter is observed as secondary to treatment, continuation of infusion should be considered). Should not be administered in patients who received intravenous AADs (class I and III) within 4 hours prior to vernakalant (risk of atrial flutter may be increased in patients receiving class I AADs). In patients with valvular heart disease, there was a higher incidence of ventricular arrhythmia events in vernakalant patients (monitor closely). Vernakalant is not recommended in patients with clinically meaningful valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis or advanced hepatic impairment. This medicinal product contains sodium; this should be taken into consideration by patients on a controlled sodium diet.