Vernakalant (United States: Not available): Drug information

(For additional information see "Vernakalant (United States: Not available): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: Canada

Brinavess

Pharmacologic Category

Antiarrhythmic Agent, Class III

Dosing: Adult

Atrial fibrillation, pharmacologic cardioversion

Atrial fibrillation, pharmacologic cardioversion:

Note: Prior to use, ensure adequate hydration, proper anticoagulation, and correct hypokalemia. Monitor patients throughout infusion(s) and for ≥2 hours after administration.

IV: Initial: 3 mg/kg over 10 minutes (maximum dose: 339 mg). If conversion to sinus rhythm does not occur within 15 minutes after the end of the initial infusion, may administer a second dose of 2 mg/kg over 10 minutes (maximum dose: 226 mg). If conversion to sinus rhythm occurs during either the initial or second dose, that dose should be continued to completion. Cumulative doses >5 mg/kg should not be administered within 24 hours; cumulative doses >565 mg have not been evaluated.

Note: Stop the infusion promptly if any of the following events occur if these events occur (shortly after the first infusion, do not administer a second dose): Sudden drop in blood pressure or heart rate, with or without symptomatic hypotension or bradycardia; hypotension; bradycardia; ECG changes (eg, clinically meaningful sinus pause, complete heart block, new bundle branch block, significant prolongation of the QRS or QT interval, changes consistent with ischemia, infarction, or ventricular arrhythmia).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary

Dosing: Hepatic Impairment: Adult

Mild to moderate hepatic impairment: No dosage adjustment necessary.

Advanced hepatic impairment: Use not recommended (has not been adequately studied).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Hypotension (4% to 13%)

Gastrointestinal: Dysgeusia (18%)

Respiratory: Sneezing (13%)

1% to 10%:

Cardiovascular: Atrial flutter (2% to 10%), bradycardia (2% to 8%), ventricular arrhythmia (≤6%), hypertension (1% to 2%), first degree atrioventricular block (1%), ventricular tachycardia (1%)

Central nervous system: Paresthesia (7%), dizziness (3% to 4%), fatigue (1% to 3%), feeling hot (2%), infusion site pain (2%)

Dermatologic: Hyperhidrosis (3%), pruritus (3%)

Gastrointestinal: Nausea (5% to 6%), oral paresthesia (2%), vomiting (1%), diarrhea (≤1%)

Respiratory: Cough (4%), nasal discomfort (2%), dyspnea (≤2%)

<1%, postmarketing, and/or case reports: Abdominal distress, abdominal pain, agitation, altered sense of smell, angina pectoris, anosmia, anxiety, arterial thrombosis, arthralgia, asphyxia, atrioventricular block, back pain, blurred vision, bowel urgency, cardiogenic shock, catheter site erythema, chest discomfort, chest pain, chills, confusion, constipation, cystitis, decreased hemoglobin, decreased serum potassium, decreased urine output, drowsiness, dyspepsia, ecchymoses, erythema, eye irritation, fever, flushing, hematuria, hyperkalemia, hyperthyroidism, hyperventilation, hypoesthesia, hypokalemia, increased blood urea nitrogen, increased gamma-glutamyl transferase, increased lacrimation, increased serum AST, increased serum creatinine, injection site pruritus, injection site reaction, insomnia, irritation at injection site, left bundle branch block, limb pain, malaise, mitral valve insufficiency, muscle spasm, musculoskeletal pain, myalgia, nasal congestion, nasopharyngitis, nodal arrhythmia, oral hypoesthesia, oropharyngeal pain, orthopnea, pain at injection site, pallor, palpitations, peripheral edema, prolonged QT interval on ECG, pulmonary edema, rales, rhinitis, rhinorrhea, right bundle branch block, sinoatrial arrest, sinus bradycardia, skin rash, supraventricular extrasystole, supraventricular tachycardia, syncope, throat irritation, upper respiratory tract infection, urinary retention, urinary tract infection, ventricular fibrillation, ventricular fibrillation, ventricular premature contractions, visual impairment, weakness, widened QRS complex on ECG, xerostomia

Contraindications

Hypersensitivity to vernakalant or any component of the formulation; severe aortic stenosis; systolic blood pressure <100 mm Hg; heart failure class NYHA III or NYHA IV; acute coronary syndrome or acute decompensated heart failure within the last 30 days; significant prolonged QT at baseline (eg, uncorrected QT >440 msec); congenital or acquired long QT syndrome; severe bradycardia, sinus node dysfunction; second- or third-degree heart block in the absence of a properly functioning pacemaker; use of intravenous class I or class III antiarrhythmics within 4 hours prior to or after vernakalant administration

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Atrial flutter: May be associated with a higher incidence of converting to atrial flutter within the first 2 hours postdose; risk is increased in patients taking class I antiarrhythmics. If hemodynamically stable atrial flutter is observed after the first infusion, the second infusion may be administered to convert to sinus rhythm. If atrial flutter occurs with signs of hemodynamic instability or development of 1:1 atrioventricular (AV) conduction, discontinue therapy and consider electrical cardioversion.

• Bradycardia: Serious bradycardia has been reported during or following infusion (most occurring soon after conversion to sinus rhythm). If bradycardia occurs, discontinue therapy promptly; however, some events of bradycardia requiring electrical pacing have been reported.

• Hypotension: Hypotension, some serious and/or severe, has been reported during and immediately following infusion. Risk is increased in patients taking a beta-blocker as chronic therapy. IV beta-blocker use is not recommended for 2 hours before or 2 hours after completion of therapy. Observe patients carefully, assessing vital signs and continuous cardiac rhythm monitoring, during infusion and for ≥2 hours after administration. If hypotension occurs or a sudden drop in BP or heart rate occurs, with or without symptomatic hypotension or bradycardia, discontinue promptly. Resuscitation equipment and the capability to place a temporary pacemaker should be readily available. Use with caution in patients with systolic BP <105 mm Hg at the time of initiation of infusion (these patients have a 3-fold increased incidence of hypotension). Risk of hypotension is increased in those with heart failure; use cautiously in those with stable NYHA Class I to II symptoms.

• QT prolongation: QT prolongation has been reported during and immediately following infusion. Use is not recommended in patients with a family history of long QT syndrome unless a diagnosis of long QT syndrome has been definitively ruled out. Discontinue use promptly if ECG changes occur (eg, clinically meaningful sinus pause, complete heart block, new bundle branch block, significant prolongation of the QRS or QT interval, changes consistent with ischemia, infarction, ventricular arrhythmia).

Disease-related concerns:

• Cardiovascular disease: Use caution in patients with HF class NYHA I or II. Use in patients with previously documented LVEF ≤35% is not recommended. Use caution in patients with valvular heart disease (higher incidence of ventricular arrhythmia and bradycardia in the first 2 hours post dose). Use is not recommended in patients with clinically meaningful hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.

• Hypokalemia: Correct potassium levels prior to use in patients with uncorrected hypokalemia (ie, serum potassium <3.5 mmol/L).

Dosage form specific issues:

• Sodium: Some products may contain sodium. Use caution in patients on a sodium controlled diet.

Other warnings/precautions:

• Appropriate use: Not recommended for conversion of atrial flutter to sinus rhythm. Patients should be anticoagulated in accordance to guidelines before and after treatment with vernakalant to reduce the risk for thromboembolic complications after return to normal sinus rhythm.

Product Availability

Not available in the US

Generic Equivalent Available: US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Brinavess: 500 mg/25 mL (25 mL)

Administration: Adult

IV: For IV infusion only in a monitored clinical setting. Do not administer by IV push or bolus. Must dilute concentrate before use. Infuse over 10 minutes using an infusion pump (preferred) or a syringe pump. If conversion to sinus rhythm occurs during either the first or second infusion, continue the infusion to completion.

Use: Labeled Indications

Note: Not approved in the United States.

Atrial fibrillation, pharmacologic cardioversion: Rapid conversion of recent onset atrial fibrillation to sinus rhythm for nonsurgical (atrial fibrillation duration ≤7 days) and postcardiac surgery patients (atrial fibrillation duration ≤3 days).

Medication Safety Issues

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP2D6 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Amiodarone: QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Carbetocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Ceritinib: QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Ceritinib. Ceritinib may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination

Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination

Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

ClomiPRAMINE: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Dabrafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

DroPERidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of DroPERidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Erythromycin (Systemic): QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Avoid concomitant use of erythromycin and class III antiarrhythmic agents. Use of erythromycin with dronedarone is specifically contraindicated. Risk X: Avoid combination

Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Etelcalcetide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination

Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination

Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Gemifloxacin: May enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination

Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification

Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Haloperidol: QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy

Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Lacosamide: Antiarrhythmic Agents (Class III) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy

Landiolol: May enhance the adverse/toxic effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk C: Monitor therapy

Levofloxacin-Containing Products (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination

Levoketoconazole: QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination

Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Methadone: QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination

Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination

OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ondansetron: QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Oxytocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

PAZOPanib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of PAZOPanib. Risk X: Avoid combination

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination

Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination

Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination

Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination

Propofol: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination

QT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of other QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination

Quizartinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination

RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination

SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Terbutaline: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Agents other than vernakalant are currently recommended when pharmacologic cardioversion is needed in pregnant females with atrial fibrillation (Regitz-Zagrosek [ESC 2018]).

Breastfeeding Considerations

It is not known if vernakalant is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.

Monitoring Parameters

Signs/symptoms of a sudden decrease in blood pressure or heart rate or significant QT prolongation for the duration of the first infusion and for at least 15 minutes after the completion of the infusion with assessment of vital signs and continuous cardiac rhythm monitoring; if a second dose is administered, monitor the same as first infusion; monitor for at least 2 hours after cessation of infusion, and until clinical and ECG parameters have stabilized; correct hypokalemia prior to initiation of therapy.

Mechanism of Action

Anti-arrhythmic that acts preferentially on the atrial with limited effects on ventricular tissues. It is a multi-ion channel blocker, which inhibits several potassium and sodium currents. This results in prolongation of atrial refractoriness and rate dependent slowing of atrial conduction to suppress atrial re-entry. It has little impact on currents involved in ventricular repolarization.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Rapid

Distribution: V_d: ~2 L/kg; extensively and rapidly distributed in the body

Protein binding: 37% to 47%

Metabolism: Hepatic, via CYP2D6 O-demethylation in CYP2D6 extensive metabolizers to the active metabolite RSD1385 (Finnin 2010) and glucuronidation in CYP2D6 poor metabolizers

Half-life elimination: ~3 hours (CYP2D6 extensive metabolizers) and ~5.5 hours (CYP2D6 poor metabolizers)

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Brinavess;
(AR) Argentina: Brinavess;
(AT) Austria: Brinavess;
(BE) Belgium: Brinavess;
(CH) Switzerland: Brinavess;
(CO) Colombia: Brinavess;
(CZ) Czech Republic: Brinavess;
(DE) Germany: Brinavess;
(ES) Spain: Brinavess;
(FI) Finland: Brinavess;
(GB) United Kingdom: Brinavess;
(GR) Greece: Brinavess;
(HK) Hong Kong: Brinavess;
(IE) Ireland: Brinavess;
(LB) Lebanon: Brinavess;
(LT) Lithuania: Brinavess;
(LV) Latvia: Brinavess;
(NL) Netherlands: Brinavess;
(NO) Norway: Brinavess;
(PL) Poland: Brinavess;
(QA) Qatar: Brinavess;
(SA) Saudi Arabia: Brinavess;
(SE) Sweden: Brinavess;
(SI) Slovenia: Brinavess;
(SK) Slovakia: Brinavess;
(ZA) South Africa: Brinavess

Brinavess (vernakalant) [product monograph]. Oakville, Ontario, Canada: Cipher Pharmaceutcals Inc; April 2019.
Camm AJ, Capucci A, Hohnloser SH, et al; AVRO Investigators. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. J Am Coll Cardiol. 2011;57(3):313-321. doi: 10.1016/j.jacc.2010.07.046. [PubMed 21232669]
Finnin M. Vernakalant: A novel agent for the termination of atrial fibrillation. Am J Health Syst Pharm. 2010;67(14):1157-1164. [PubMed 20592320]
Kowey PR, Dorian P, Mitchell LB, et al; Atrial Arrhythmia Conversion Trial Investigators. Vernakalant hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery: a randomized, double-blind, placebo-controlled trial. Circ Arrhythm Electrophysiol. 2009;2(6):652-659. doi: 10.1161/CIRCEP.109.870204. [PubMed 19948506]
Pratt CM, Roy D, Torp-Pedersen C, et al; Atrial Arrhythmia Conversion Trial (ACT-III) Investigators. Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation. Am J Cardiol. 2010;106(9):1277-1283. doi: 10.1016/j.amjcard.2010.06.054. [PubMed 21029824]
Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165-3241. [PubMed 30165544]
Roy D, Pratt CM, Torp-Pedersen C, et al; Atrial Arrhythmia Conversion Trial Investigators. Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial. Circulation. 2008;117(12):1518-1525. doi: 10.1161/CIRCULATIONAHA.107.723866. [PubMed 18332267]
Simon A, Niederdoeckl J, Skyllouriotis E, et al. Vernakalant is superior to ibutilide for achieving sinus rhythm in patients with recent-onset atrial fibrillation: a randomized controlled trial at the emergency department. Europace. 2017;19(2):233-240. doi: 10.1093/europace/euw052. [PubMed 28175295]

Topic 116881 Version 80.0

خرید پکیج

Vernakalant (United States: Not available): Drug information