Brinavess 20 mg/ml

/ Tzamal

This formulation should be administered by intravenous infusion, in a monitored clinical setting appropriate for cardio-version. Only a well-qualified healthcare professional should administer this formulation and should frequently monitor the patient for the duration of the infusion and for at least 15 minutes after the completion of the infusion for signs and symptoms of a sudden decrease in blood pressure or heart rate.
This agent is dosed by patient body weight, with a maximum calculated dose based upon 113 kg.
The recommended initial infusion is 3 mg/kg to be infused over a 10 minute period. For patients weighing ≥ 113 kg, do not exceed the maximum initial dose of 339 mg (84.7 ml of 4 mg/ml solution).
If conversion to sinus rhythm does not occur within 15 minutes after the end of the initial infusion, a second 10 minute infusion of 2 mg/kg may be administered. For patients weighing ≥ 113 kg, do not exceed the maximum second infusion of 226 mg (56.5 ml of 4 mg/ml solution).
Cumulative doses of greater than 5 mg/kg should not be administered within 24 hours. There are no clinical data on repeat doses after the initial and second infusions. By 24 hours there appears to be insignificant levels of vernakalant.
If conversion to sinus rhythm occurs during either the initial or second infusion, that infusion should be continued to completion. If haemodynamically stable atrial flutter is observed after the initial infusion, the second infusion of Vernakalant may be administered as patients may convert to sinus rhythm. An infusion pump is the preferred delivery device. However, a syringe pump is acceptable provided that the calculated volume can be accurately given within the specified infusion time.
Do not administer as an intravenous push or bolus. Recommended diluents are 0.9% Sodium Chloride for Injection, Lactated Ringers for Injection, or 5% Glucose for Injection.
Preparationof infusion: Step 1: Visually inspect the drug vials for particulate matter and discolouration before administration. Do not use any vials exhibiting particulate matter or discolouration. Note: concentrate for solution for infusion ranges from colourless to pale yellow. Variations of colour within this range do not affect potency.
Step 2: Dilution of concentrate. To ensure proper administration, a sufficient amount of the drug should be prepared at the outset of therapy to deliver the initial and second infusion should it be warranted. Create a solution with a concentration of 4mg/ml following the dilution guidelines below:
Patients ≤ 100 kg: 25 ml of this drug 20 mg/ml is added to 100 ml of diluent.
Patients > 100 kg: 30 ml of this drug 20 mg/ml is added to 120 ml of diluent.
Step 3: Inspect solution: The diluted sterile solution should be clear, colourless to pale yellow. Visually re-inspect the solution for particulate matter and discolouration before administering.
Method of administration: The drug vials are for single use only and must be diluted prior to administration.
Step 4: Administration of the initial infusion: The initial infusion of the drug is administered as a 3 mg/kg dose over 10 minutes. During this period, the patient should be carefully monitored for any signs or symptoms of a sudden decrease in blood pressure or heart rate. If such signs develop, with or without symptomatic hypotension or bradycardia, the infusion should be stopped immediately.
Step 5: Patient observation Conversion to sinus rhythm has not occurred, observe the patient’s vital signs and cardiac rhythm for an additional 15 minutes.
Step 6: Administration of second infusion If conversion to sinus rhythm did not occur with the initial infusion or within the 15 minute observation period, administer a 2 mg/kg second infusion over 10 minutes. Cumulative doses above 565 mg have not been evaluated.
Paediatric population: There is no relevant use ofthis drug in children and adolescents < 18 years of age in the current indication and therefore should not be used in this population.

Rapid conversion of recent onset atrial fibrillation to sinus rhythm in adults who are hemodynamically stable.
For non-surgery patients: atrial fibrillation ≤ 7 days duration.
For post-cardiac surgery patients: atrial fibrillation ≤ 3 days duration.

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 msec), 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, as well as in the first 4 hours after, Vernakalant administration.
Acute coronary syndrome (including myocardial infarction) within the last 30 days.

Cases of serious hypotension have been reported during and immediately following infusion. Patients should be carefully observed for the entire duration of the infusion and for at least 15 minutes after completion of the infusion with assessment of vital signs and continuous cardiac rhythm monitoring.
If any of the following signs or symptoms occurs, the administration should be discontinued and these patients should receive appropriate medical management:
A sudden drop in blood pressure or heart rate, with or without symptomatic hypotension or bradycardia. Hypotension, Bradycardia, 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 ischaemia or infarction and ventricular arrhythmia).
If these events occur during the first infusion of the drug , patients should not receive the second dose of the drug.
The patient should be further monitored for 2 hrs. after the start of infusion and until clinical and ECG parameters have stabilised.
Direct-current cardioversion may be considered for patients who do not respond to therapy. There is no clinical experience with direct-current cardioversion under two hours postdose.
Prior to attempting pharmacological cardioversion, ensure that patients are adequately hydrated and haemodynamically 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 of this formulation.
Hypotension: Hypotension can occur in a small number of patients (vernakalant 7.6%, placebo 5.1%). Hypotension typically occurs early, either during the infusion or early after the end of the infusion, and can usually be corrected by standard supportive measures. Uncommonly, cases of severe hypotension have been observed. Patients with congestive heart failure (CHF) have been identified as a population at higher risk for hypotension.
The patient is required to be monitored for signs and symptoms of a sudden decrease in blood pressure or heart rate for the duration of the infusion and for at least 15 minutes after the completion of the infusion.
Congestive Heart Failure: Patients with CHF showed a higher overall incidence of hypotensive events, during the first 2 hours after dose in patients treated with vernakalant compared to patients receiving placebo (16.1% versus 4.7%, respectively).
Atrial Flutter: This agent was not found to be effective in converting typical primary atrial flutter to sinus rhythm. Patients receiving this drug have a higher incidence of converting to atrial flutter within the first 2 hours post-dose.
See prescribing information for full details.

Dysgeusia, Paraesthesia, dizziness, headache, hypoaesthesia, burning sensation, parosmia, somnolence, vasovagal, bradycardia, atrial flutter, nausea, vomiting cough.
See prescribing information for full details.

No formal interaction studies have been undertaken with vernakalant injection. Within the clinical development program, oral maintenance antiarrhythmic therapy was halted for a minimum of 2 hours afterthis drug  administration. Resumption or initiation of oral maintenance antiarrhythmic therapy after this time period can be considered.
See prescribing information for full details.

Pregnancy: There are no data from the use of vernakalant hydrochloride in pregnant women.
Lactation: It is unknown whether vernakalant/metabolites are excreted in human milk.
See prescribing information for full details. 

One patient who received 3 mg/kg of the drug over 5 minutes (instead of the recommended 10 minutes) developed haemodynamically stable wide complex tachycardia which resolved without sequelae. 

Storage: The diluted sterile concentrate is chemically and physically stable for 12 hours at or below 25°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Compatibility: This medicinal product must not be mixed with other medicinal products except: 0.9% Sodium Chloride for injection, Lactated Ringers for Injection, or 5% Glucose for Injection.
Excipient with known effect: Each vial of 200 mg contains approximately 1.4 mmol (32 mg) sodium. Each vial of 500 mg contains approximately 3.5 mmol (80 mg) of sodium. Each administered milliliter of the diluted solution contains approximately 3.5 mg of sodium (sodium chloride 9 mg/ml (0.9%) solution for injection), 0.64 mg sodium (Glucose injection 5%) or 3.2 mg sodium (Lactated Ringers for Injection).