Vernakalant

Indications

Vernakalant (Brinavess®) is indicated for rapid conversion of recent-onset atrial fibrillation (AF) to sinus rhythm in adults who are:

• Non-surgery patients with AF ≤7 days duration
• Post–cardiac surgery patients with AF ≤3 days duration

A pre-infusion checklist is supplied with the product.

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 <3.5 mmol/l), potassium levels should be corrected prior to use of vernakalant.

Contraindications

1. Hypersensitivity / allergy to active substance or ingredients of the concentrate
2. Clinical:
   1. Severe aortic stenosis
   2. SBP <100 mm Hg
   3. LVF (NYHA iii or iv) or documented LVEF ≤35%
   4. Prolonged QT at baseline (uncorrected >440 msec)
   5. Severe bradycardia or Sinus Node dysfunction
   6. 2nd or 3rd degree heart block (in absence of a pacemaker)
   7. Use of iv rhythm-control antiarrhythmics (class I and class III) within 4 hours prior to, and in the first 4 hours after, vernakalant administration
   8. ACS (including AMI) within last 30 days
   9. Clinically meaningful valvular stenosis
   10. HOCM or restrictive cardiomyopathy/pericarditis
   11. Advanced hepatic impairment

Preparation

• Vernakalant concentrate must be diluted (0.9% NaCl) prior to administration to produce a solution with a vernakalant hydrochloride concentration of 4 mg/ml
• x1 (25ml) vial (25ml vial = 500 mg Vernakalant) added to 100ml 0.9% saline = 4mg/ml solution then dose as per table
• Give via iv infusion (not push) over 10 min in cardiac monitored area
• Stop infusion (and no second dose) if bradycardia or ↓BP
• A pre-infusion checklist should be used (incl. correct hypokalaemia)

1. Visually inspect concentrate vials for particulate matter or discolouration:
   • Brinavess® ranges from colourless to pale yellow. Variations of colour within this range do not affect potency
   • Do not use vials if particulate matter / discolouration is seen
2. Dilute concentrate:
   • Use the table right/below to dilute Brinavess® to a concentration of 4 mg/ml. Recommended diluents are 0.9% Sodium Chloride for Injection, Lactated Ringers for Injection, or 5% Glucose for Injection. The final volume of the diluted solution will be enough for both the initial and second infusions (if necessary)
3. Inspect the diluted solution for particulate matter or discolouration:
   • The diluted sterile solution should be clear and colourless to pale yellow
   • Do not use if particulate matter or discolouration is observed
4. Administer diluted solution for initial infusion:
   • 1 vial (25ml) plus 100ml of 0.9% NaCl = solution is ready - infuse as per table
   • The initial infusion of Brinavess® is given as a 3-mg/kg dose over 10 minutes according to the dosage table
   • During infusion, monitor for ↓BP or ↓HR / arrhythmia. If signs, stop infusion and treat appropriately
   • If conversion to sinus rhythm occurs during either the initial or second infusion, that infusion should be continued through completion
   • If haemodynamically stable atrial flutter is observed after the initial infusion, the second infusion of Brinavess® may be administered, as patients may convert to sinus rhythm
5. Observe patient:
   • Continue careful observation with assessment of vital signs and continuous cardiac rhythm monitoring for at least 15 minutes
   • If conversion to sinus rhythm did not occur with the initial infusion or within the 15-minute observation period, administer a second infusion of Brinavess®
6. Administer second infusion (if necessary):
   • The second infusion of Brinavess® is given as a 2-mg/kg dose over 10 minutes according to the dosage table
   • Continue careful observation with assessment of vital signs and continuous cardiac rhythm monitoring for at least 15 minutes
   • The patient should be further monitored for 2 hours after the start of infusion and until clinical and ECG parameters have stabilised

Initial Infusion = 3 mg/kg over 10 min.			Second Infusion = 2 mg/kg over 10 min. (if nec.)
Patient Wt (kg)	Infusion Vol. of Diluted Solution (ml)	Infusion Rate (ml/h)	Infusion Vol. of Diluted Solution (ml)	Infusion Rate (ml/h)
38 kg	28.5 ml	171 ml/h	19.0 ml	114 ml/h
39 kg	29.2 ml	175 ml/h	19.5 ml	117 ml/h
40 kg	30.0 ml	180 ml/h	20.0 ml	120 ml/h
41 kg	30.7 ml	184 ml/h	20.5 ml	123 ml/h
42 kg	31.5 ml	189 ml/h	21.0 ml	126 ml/h
43 kg	32.2 ml	193 ml/h	21.5 ml	129 ml/h
44 kg	33.0 ml	198 ml/h	22.0 ml	132 ml/h
45 kg	33.7 ml	202 ml/h	22.5 ml	135 ml/h
46 kg	34.5 ml	207 ml/h	23.0 ml	138 ml/h
47 kg	35.2 ml	211 ml/h	23.5 ml	141 ml/h
48 kg	36.0 ml	216 ml/h	24.0 ml	144 ml/h
49 kg	36.7 ml	220 ml/h	24.5 ml	147 ml/h
50 kg	37.5 ml	225 ml/h	25.0 ml	150 ml/h
51 kg	38.2 ml	229 ml/h	25.5 ml	153 ml/h
52 kg	39.0 ml	234 ml/h	26.0 ml	156 ml/h
53 kg	39.7 ml	238 ml/h	26.5 ml	159 ml/h
54 kg	40.5 ml	243 ml/h	27.0 ml	162 ml/h
55 kg	41.2 ml	247 ml/h	27.5 ml	165 ml/h
56 kg	42.0 ml	252 ml/h	28.0 ml	168 ml/h
57 kg	42.7 ml	256 ml/h	28.5 ml	171 ml/h
58 kg	43.5 ml	261 ml/h	29.0 ml	174 ml/h
59 kg	44.2 ml	265 ml/h	29.5 ml	177 ml/h
60 kg	45.0 ml	270 ml/h	30.0 ml	180 ml/h
61 kg	45.7 ml	274 ml/h	30.5 ml	183 ml/h
62 kg	46.5 ml	279 ml/h	31.0 ml	186 ml/h
63 kg	47.2 ml	283 ml/h	31.5 ml	189 ml/h
64 kg	48.0 ml	288 ml/h	32.0 ml	192 ml/h
65 kg	48.7 ml	292 ml/h	32.5 ml	195 ml/h
66 kg	49.5 ml	297 ml/h	33.0 ml	198 ml/h
67 kg	50.2 ml	301 ml/h	33.5 ml	201 ml/h
68 kg	51.0 ml	306 ml/h	34.0 ml	204 ml/h
69 kg	51.7 ml	310 ml/h	34.5 ml	207 ml/h
70 kg	52.5 ml	315 ml/h	35.0 ml	210 ml/h
71 kg	53.2 ml	319 ml/h	35.5 ml	213 ml/h
72 kg	54.0 ml	324 ml/h	36.0 ml	216 ml/h
73 kg	54.7 ml	328 ml/h	36.5 ml	219 ml/h
74 kg	55.5 ml	333 ml/h	37.0 ml	222 ml/h
75 kg	56.2 ml	337 ml/h	37.5 ml	225 ml/h
76 kg	57.0 ml	342 ml/h	38.0 ml	228 ml/h
77 kg	57.7 ml	346 ml/h	38.5 ml	231 ml/h
78 kg	58.5 ml	351 ml/h	39.0 ml	234 ml/h
79 kg	59.2 ml	355 ml/h	39.5 ml	237 ml/h
80 kg	60.0 ml	360 ml/h	40.0 ml	240 ml/h
81 kg	60.7 ml	364 ml/h	40.5 ml	243 ml/h
82 kg	61.5 ml	369 ml/h	41.0 ml	246 ml/h
83 kg	62.2 ml	373 ml/h	41.5 ml	249 ml/h
84 kg	63.0 ml	378 ml/h	42.0 ml	252 ml/h
85 kg	63.7 ml	382 ml/h	42.5 ml	255 ml/h
86 kg	64.5 ml	387 ml/h	43.0 ml	258 ml/h
87 kg	65.2 ml	391 ml/h	43.5 ml	261 ml/h
88 kg	66.0 ml	396 ml/h	44.0 ml	264 ml/h
89 kg	66.7 ml	400 ml/h	44.5 ml	267 ml/h
90 kg	67.5 ml	405 ml/h	45.0 ml	270 ml/h
91 kg	68.2 ml	409 ml/h	45.5 ml	273 ml/h
92 kg	69.0 ml	414 ml/h	46.0 ml	276 ml/h
93 kg	69.7 ml	418 ml/h	46.5 ml	279 ml/h
94 kg	70.5 ml	423 ml/h	47.0 ml	282 ml/h
95 kg	71.2 ml	427 ml/h	47.5 ml	285 ml/h
96 kg	72.0 ml	432 ml/h	48.0 ml	288 ml/h
97 kg	72.7 ml	436 ml/h	48.5 ml	291 ml/h
98 kg	73.5 ml	441 ml/h	49.0 ml	294 ml/h
99 kg	74.2 ml	445 ml/h	49.5 ml	297 ml/h
100 kg	75.0 ml	450 ml/h	50.0 ml	300 ml/h
101 kg	75.7 ml	454 ml/h	50.5 ml	303 ml/h
102 kg	76.5 ml	459 ml/h	51.0 ml	306 ml/h
103 kg	77.2 ml	463 ml/h	51.5 ml	309 ml/h
104 kg	78.0 ml	468 ml/h	52.0 ml	312 ml/h
105 kg	78.7 ml	472 ml/h	52.5 ml	315 ml/h
106 kg	79.5 ml	477 ml/h	53.0 ml	318 ml/h
107 kg	80.2 ml	481 ml/h	53.5 ml	321 ml/h
108 kg	81.0 ml	486 ml/h	54.0 ml	324 ml/h
109 kg	81.7 ml	490 ml/h	54.5 ml	327 ml/h
110 kg	82.5 ml	495 ml/h	55.0 ml	330 ml/h
111 kg	83.2 ml	499 ml/h	55.5 ml	333 ml/h
112 kg	84.0 ml	504 ml/h	56.0 ml	336 ml/h
113 kg	84.7 ml	508 ml/h	56.5 ml	339 ml/h

Dosage

Body weight: ≥40 kg and <113 kg

• Infusion 3 mg/kg over 10 minutes
• If no cardioversion after 15 min, give a further 2mg/kg infusion over 10 minutes

Body weight ≥113kg

• Infusion : Total dose = 339 mg over 10 minutes
• If no cardioversion after 15 min, give a further 226 mg infusion over 10 minutes

If conversion to sinus rhythm occurs during either the initial or second infusion, that infusion should be continued through 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.

Other intravenous rhythm-control antiarrhythmics (class I and class III) are contraindicated within 4 hours prior to, as well as in the first 4 hours after, vernakalant.

Resumption or initiation of oral-maintenance antiarrhythmic therapy can be considered 2 hours after administration.