Vernakalant is a medication used in the treatment of atrial fibrillation, a condition characterized by irregular heartbeat. It belongs to a class of drugs called antiarrhythmics.
Vernakalant works by blocking certain channels in the heart's cells, which helps to restore normal heart rhythm. It's often used in situations where rapid conversion to normal sinus rhythm is desired, such as in acute episodes of atrial fibrillation.
Vernakalant (Brinavess) is a sodium and Potassium channel blocker. The action of vernakalant is heart rate and membrane potential-dependent.
It is used for the treatment of:
- 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)
Vernakalant Dose in Adults
Vernakalant Dose in the treatment of Atrial fibrillation (pharmacologic cardioversion):
- The usual starting dose is 3 milligrams per kilogram of body weight, given through a vein (intravenously) over a 10-minute period.
- The maximum dose for this initial infusion is 339 milligrams.
- If the heart rhythm doesn't return to normal within 15 minutes after the first infusion, a second infusion of 2 milligrams per kilogram (up to a maximum of 226 milligrams) can be given over another 10 minutes.
- If the person has a stable form of atrial flutter (another type of irregular heart rhythm) after the first infusion, the second infusion can still be given to try to restore normal rhythm.
- It's important not to exceed a total dose of 5 milligrams per kilogram within 24 hours, and doses larger than 565 milligrams in total haven't been studied.
Note: It's important to promptly stop the infusion of vernakalant and avoid giving a second dose if any of these events happen shortly after the first infusion:
- A sudden drop in blood pressure or heart rate, whether or not there are symptoms of low blood pressure or slow heart rate.
- Low blood pressure (hypotension).
- Slow heart rate (bradycardia).
- Changes in the electrocardiogram (ECG) readings, such as a significant pause in the heart rhythm (sinus pause), complete blockage of electrical signals in the heart (complete heart block), development of a new bundle branch block, substantial prolongation of the QRS or QT interval, or changes indicating reduced blood flow to the heart muscle (ischemia), heart attack (infarction), or abnormal heart rhythm in the ventricles (ventricular arrhythmia).
These signs could indicate a serious reaction to the medication, so it's crucial to stop the infusion and seek medical attention if any of them occur.
Vernakalant Dose in Children
Not recommended.
Pregnancy Risk factor: C
- Adverse effects have been noted in animal studies regarding the use of vernakalant during pregnancy.
- Consequently, other treatment options are suggested for pregnant women with atrial fibrillation who require pharmacologic cardioversion.
Vernakalant use during breastfeeding:
- Since it's uncertain whether vernakalant passes into breast milk, and because of the potential for severe adverse effects in breastfed infants, the manufacturer does not recommend breastfeeding while using this medication.
Vernakalant Dose in Renal Disease:
No dosage adjustment is needed for vernakalant in patient with kidney disease.
Vernakalant Dose in Liver Disease:
- No adjustment to the dosage of vernakalant is required for patient with liver disease.
- Caution should be exercised, particularly in cases of advanced hepatic impairment, as the effects of vernakalant in such conditions have not been thoroughly studied.
Common Side Effects of Vernakalant Include:
- Cardiovascular:
- Hypotension
- Gastrointestinal:
- Dysgeusia
- Respiratory:
- Sneezing
Less Common Side Effects of Vernakalant Include:
- Cardiovascular:
- Atrial Flutter
- Bradycardia
- Ventricular Arrhythmia
- Hypertension
- First Degree Atrioventricular Block
- Ventricular Tachycardia
- Central Nervous System:
- Paresthesia
- Dizziness
- Fatigue
- Feeling Hot
- Infusion Site Pain
- Dermatologic:
- Hyperhidrosis
- Pruritus
- Gastrointestinal:
- Nausea
- Oral Paresthesia
- Vomiting
- Diarrhea
- Respiratory:
- Cough
- Nasal Discomfort
- Dyspnea
Contraindication to Vernakalant Include:
- Vernakalant should not be used if someone is allergic to it or any of its ingredients, has severe narrowing of the aortic valve, has very low blood pressure (systolic blood pressure less than 100 mm Hg), or has advanced heart failure (NYHA class III or IV).
- It's also not recommended if someone has had a heart attack or worsening heart failure within the past month, has a significantly prolonged QT interval on their heart's electrical tracing at the start of treatment, or has certain heart rhythm problems like long QT syndrome, very slow heart rate, or certain types of heart block without a functioning pacemaker.
- Additionally, it's not advisable to use vernakalant if someone has received certain other heart medications within four hours before or after using vernakalant.
Warnings and Precautions
Atrial flutter
- Atrial flutter might happen more often in the first two hours after taking vernakalant, especially in people who are also using class I anti-arrhythmic drugs.
- It's important to keep a close eye on patients during this time.
- If atrial flutter occurs and causes signs of unstable blood flow or if there's a risk of a condition called 1:1 atrioventricular (AV) conduction, stopping vernakalant should be considered.
Bradycardia
- Serious slowing of the heart rate, known as bradycardia, has been reported during or after the infusion of vernakalant, with most cases happening shortly after the heart returns to a normal rhythm.
- If bradycardia occurs, it's important to stop the therapy right away.
- However, in some cases, bradycardia was severe enough to need electrical pacing.
CNS effects
- Vernakalant can lead to depression of the central nervous system (CNS), potentially affecting both physical and mental abilities.
- Patients should be advised to be cautious when performing tasks that require mental alertness, such as operating machinery or driving vehicles.
Hypotension
- Hypotension, including severe cases, has been reported during and immediately after the infusion of vernakalant.
- It's crucial to closely monitor patients during the infusion and for at least two hours afterward.
- If hypotension occurs, or if there's a sudden drop in blood pressure or heart rate with or without symptoms, the infusion should be stopped promptly.
- Equipment for resuscitation and the ability to insert a temporary pacemaker should be readily available.
- Vernakalant should be used with caution in patients with a systolic blood pressure (SBP) below 105 mm Hg at the start of the infusion, as they have a higher risk of hypotension.
- Its use is not recommended if SBP is below 100 mmHg.
- The risk of hypotension is higher in patients with heart failure; therefore, it should be used cautiously in those with mild to moderate symptoms (NYHA Class I to II), but it's contraindicated in those with severe symptoms (NYHA Class III or IV).
Extension of QT
- There's a risk of prolonging the QT interval (the time it takes for the heart to recharge between beats) with vernakalant use.
- It's not recommended for patients with a family history of long QT syndrome unless a definite diagnosis of the syndrome has been ruled out.
- If there are any changes in the electrocardiogram (ECG), such as a significant prolongation of the QT interval, or other concerning signs like pauses in the heart rhythm, complete heart block, or new bundle branch block, vernakalant should be stopped promptly.
Cardiovascular disease
- In patients with cardiovascular disease, it's important to exercise caution when using vernakalant.
- For those with heart failure in NYHA classes I or II, it's necessary to be careful.
- However, using vernakalant isn't advised for patients with previously documented low left ventricular ejection fraction (LVEF) of 35% or less.
- Additionally, caution is needed in patients with valvular heart disease, as there's a higher risk of ventricular arrhythmia and bradycardia in the first two hours after taking the medication.
- Vernakalant should not be used in patients with clinically significant hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
- Moreover, it's contraindicated in those with heart failure in NYHA classes III to IV.
Hepatic impairment
- For individuals with advanced liver problems, using vernakalant is not recommended because its effects in such cases have not been sufficiently studied.
Hypokalemia
- Before starting vernakalant treatment, it's important to ensure that patients with low potassium levels (hypokalemia) have their potassium levels corrected.
- This means that if the level of potassium in the blood is below 3.5 mmol/L, it should be brought back to normal levels before starting vernakalant therapy.
- Maintaining proper potassium levels is crucial for the safe and effective use of the medication.
Vernakalant: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Lacosamide |
Lacosamide's harmful or toxic effects may be exacerbated by antiarrhythmic agents (Class III). It may be more likely to have bradycardia, ventricular tachyarrhythmias, or a longer PR interval. |
|
Lidocaine (Topical) |
Antiarrhythmic medications' ability to cause arrhythmias may be increased (Class III). The serum content of lidocaine may rise in response to Class III antiarrhythmic drugs (Topical). Amiodarone and dronedarone are notably affected by this mechanism. |
|
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. |
|
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 Factor D (Consider therapy modification) |
|
|
Amiodarone |
Amiodarone's QTcprolonging action may be strengthened by Class III Antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
|
Azithromycin (Systemic) |
The QTc-prolonging action of azithromycin may be enhanced by QT-prolonging agents (Highest Risk) (Systemic). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations. |
|
Chloroquine |
The QTc-prolonging action of chloroquine may be strengthened by QT-prolonging agents (Highest Risk). Management: Take into account different pairings. Watch for ventricular arrhythmias and a prolonged QTc interval if they occur together. Patients who have other QTc prolongation risk factors may be significantly more at risk. |
|
Clofazimine |
Clofazimine's ability to prolong QTc may be enhanced by QT-prolonging Agents (Highest Risk). Management: Take into account different pairings. Watch for ventricular arrhythmias and a prolonged QTc interval if they occur together. Patients who have other QTc prolongation risk factors may be significantly more at risk. |
|
CloZAPine |
CloZAPine's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account different pairings. Patients who have additional risk factors are probably more prone to these toxicities. |
|
Droperidol |
Droperidol's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. |
|
Encorafenib |
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. |
|
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. |
|
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. |
|
Gadobenate Dimeglumine |
Management: Take into account substitutes to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
|
Gilteritinib |
might make QT-prolonging agents' impact on QTc longer (Highest Risk). Management: Take into account alternatives to this fusion. If usage is required, keep an eye out for arrhythmias and a prolonged QTc interval. |
|
Halofantrine |
Halofantrine's ability to prolong QTc may be amplified by the presence of QT-prolonging agents (Highest Risk). Management: Consider the potential drawbacks of this merger. Watch for cardiac arrhythmias and a prolonged QTc interval, if present. Patients who have extra risk factors may be even more susceptible to QTc prolongation. |
|
Haloperidol |
The QTcprolonging action of haloperidol may be enhanced by QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
|
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. |
|
Methadone |
QT-prolonging Class III Antiarrhythmics (Highest Risk) may enhance the QTcprolonging 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. |
|
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. |
|
OLANZapine |
OLANZapine's ability to prolong QTc may be enhanced by QT-prolonging factors. Management: Take into account substitutes for this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, etc. |
|
Ondansetron |
The QTcprolonging action of ondansetron may be enhanced by Class III antiarrhythmics. Management: Take into account substitutes for this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
|
Osimertinib |
The QTc-prolonging action of osimertinib may be strengthened by QT-prolonging agents. Management: Take into account different pairings. Patients who have additional risk factors are probably more prone to these toxicities. |
|
Pentamidine (Systemic) |
The QTc-prolonging action of pentamidine may be enhanced by QT-prolonging agents. Management: Take into account different pairings. Watch for ventricular arrhythmias and a prolonged QTc interval if they occur together. Patients who have other QTc prolongation risk factors may be significantly more at risk. |
|
Pilsicainide |
Pilsicainide's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
|
Propafenone |
might intensify the QT-prolonging effects of class III antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
|
QT-prolonging Kinase Inhibitors (Highest Risk) |
Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
|
QT-prolonging Miscellaneous Agents (Highest Risk) |
Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. QT-prolonging Class III Antiarrhythmics may increase the QTc-prolonging effects of QT-prolonging Miscellaneous Agents. |
|
RisperiDONE |
The CNS depressive action of RisperiDONE may be enhanced by QT-prolonging Agents (Highest Risk). The QTc-prolonging action of RisperiDONE may be strengthened by QT-prolonging Agents (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. |
|
Sodium Stibogluconate |
QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sodium Stibogluconate. 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. |
|
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 Factor X (Avoid combination) |
|
|
Citalopram |
Citalopram may have a stronger QTc-prolonging impact when used with QT-prolonging Agents. |
|
Clarithromycin |
Clarithromycin's ability to prolong QTc may be enhanced by QT-prolonging agents. |
|
Domperidone |
The QTc-prolonging action of Domperidone may be strengthened by QT-prolonging Agents. |
|
Erythromycin (Systemic) |
The QTc-prolonging action of erythromycin may be enhanced by QT-prolonging Class III Antiarrhythmics. Systemic erythromycin may enhance the impact of QT-prolonging Class III antiarrhythmic. The serum concentration of QT-prolonging Class III Antiarrhythmics may be increased by systemic erythromycin. Management: According to the dronedarone US prescription instructions and a separate interaction monograph, using erythromycin in combination with dronedarone is not recommended. |
|
Fingolimod |
might intensify the QT-prolonging effects of class III antiarrhythmics |
|
Flupentixol |
Flupentixol's ability to prolong QTc may be enhanced by QT-prolonging Agents |
|
Gemifloxacin |
might intensify the QT-prolonging effects of class III antiarrhythmics |
|
Levofloxacin-Containing Products (Systemic) |
may increase the QTc-prolonging impact of class III antiarrhythmics with a long QTc |
|
Moxifloxacin (Systemic |
Moxifloxacin's ability to prolong QTc may be enhanced by QT-prolonging agents |
|
Nilotinib |
The QTc-prolonging action of nilotinib may be strengthened by QT-prolonging agents |
|
Pimozide |
The QTc-prolonging action of pimozide may be strengthened by QT-prolonging agents. Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations. |
|
Piperaquine |
QT-prolonging Agents may enhance the QTc-prolonging effect of Piperaquine. |
|
Probucol |
QT-prolonging Agents may enhance the QTc-prolonging effect of Probucol. |
|
QT-prolonging Class IA Antiarrhythmics (Highest Risk) |
May enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics |
|
QT-prolonging Class III Antiarrhythmics (Highest Risk) |
may intensify the QTc-prolonging effects of further QT-prolonging Class III antiarrhythmics |
|
QUEtiapine |
The QTc-prolonging action of quetiapine may be enhanced by QT-prolonging agents |
|
Ribociclib |
The QTc-prolonging action of ribociclib may be strengthened by QT-prolonging Agent |
|
Sparfloxacin |
The QTc-prolonging action of sparfloxacin may be enhanced by QT-prolonging agents |
|
Thioridazine |
Thioridazine's ability to prolong QTc may be enhanced by QT-prolonging agents |
Monitor:
- During First Infusion and After:
- Watch for signs of sudden blood pressure or heart rate drop.
- Look for significant QT interval prolongation.
- Assess vital signs and continuously monitor heart rhythm.
- After First Infusion and Second Dose (if given):
- Continue monitoring during the second infusion, if needed.
- After Cessation of Infusion:
- Monitor for at least 2 hours after stopping the infusion.
- Continue monitoring until clinical and ECG parameters stabilize.
Potassium Levels:
- Before Starting Therapy:
- Ensure potassium levels are normal.
- Correct hypokalemia (low potassium levels) if present (serum potassium <3.5 mmol/L).
How to administer Vernakalant?
Intravenous (IV) Infusion:
- Only administer via IV infusion in a monitored clinical setting.
- Do not give as an IV push or bolus.
- Dilute the concentrate before use.
- Infuse over 10 minutes using either an infusion pump (preferred) or a syringe pump.
- If conversion to normal sinus rhythm happens during the first or second infusion, continue the infusion until completed.
Mechanism of action of Vernakalant:
- Vernakalant is a medication that targets irregular heart rhythms, especially in the atria, the upper chambers of the heart, without affecting the lower chambers much.
- It works by blocking certain channels for potassium and sodium ions in the heart cells, which helps to make the atria less likely to start beating irregularly again.
- This action makes the heart's upper chambers take longer to recover after each beat and slows down how quickly the irregular rhythm spreads, helping to stop the problem of the heart beating in circles.
- It doesn't affect the lower chambers of the heart much, where the heart's electrical recovery happens after each beat.
Onset of Action:
- Begins working quickly after administration.
Distribution:
- Rapidly spreads throughout the body, with a distribution volume of about 2 liters per kilogram (kg).
Protein Binding:
- About 37% to 47% of the drug binds to proteins in the blood.
Metabolism:
- Processed by the liver, primarily through a pathway called CYP2D6 O-demethylation, forming an active metabolite called RSD1385 in people who metabolize drugs extensively through CYP2D6.
- In individuals who are poor metabolizers through CYP2D6, it undergoes glucuronidation as an alternative pathway.
Half-life Elimination:
- Lasts approximately 3 hours in individuals who metabolize drugs extensively through CYP2D6.
- Lasts around 5.5 hours in individuals who are poor metabolizers through CYP2D6.
International Brands of Vernakalant:
- Brinavess
Vernakalant Brands in Pakistan:
No brands available in Pakistan.
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