Ibutilide is an antiarrhythmic drug that was recently marketed for the rapid conversion of atrial fibrillation and atrial flutter. After intravenous administration, ibutilide is moderately effective in achieving prompt cardioversion to sinus rhythm, with greater efficacy in patients who have atrial flutter. Like other drugs that prolong ventricular repolarization, ibutilide administration carries a risk of excessive QT prolongation, or the acquired long-QT syndrome, with associated polymorphic ventricular tachycardia (torsade de pointes), necessitating careful patient selection and clinical monitoring during drug administration.

1. Zuventus Healthcare Ltd
Ibutilide
“The Pure Class III Antiarrhythmic”

2. Ibutilide
 Ibutilide is the first 'pure' class III anti-arrhythmic drug to be
available. [1]
 Approved by the USFDA in Dec.1995
 June 2016 (Zuventus Health Care Ltd) received manufacturing &
marketing approval from DCGI India.
 API as well as finished product developed through “in house R&D”
 Marketed as “Fibricor”
1. Drugs. 1997 Aug;54(2):312-30.

3. “Pure Class III”
• Ibutilide: “cardiac electrophysiological actions” Only.
• Ibutilide: "Pure" action potential–prolonging drug
• It has no “negative inotropic” effects
Goodman & Gilman's The Pharmacological Basis of Therapeutics - 12th Ed
Amiodarone Dronadarone and sotalol are
mixed acting class-III drugs.
Sotalol: Has class II and III activities
Amiodarone: Has Class I, II, III and IV activities and
has multiple cardiac (electrophysiologic
characteristics of all 4 classes) & systemic side
effects.
Dronaderon: Similar to Amiodarone

4. Ibutilide
Formula: C22H38N2O5S
Chemical Name: Methanesulfonamide, N-{4-{4-(ethylheptylamino)-1- hydroxybutyl}phenyl}, (+) (-),
(E)-2-butenedioate (1:0.5) (hemifumarate salt)
Chemistry

5. Unique mechanism of action
• Ibutilide, at nanomolar concentrations (10-8), “prolongs repolarization by
activation of a slow, inward current (predominantly sodium).”
• It blocks Potassium channels at 1000 times concentration i.e. (10-5)
• Plasma levels achieved after 1mg infusion are in the range of (10-8)
• This mechanism of action is “unique among available class III drugs”
Naccarelli GV. Am J Cardiol. 1996 Oct 17;78(8A):12-6.
Ibutilide does not have a sodium-
blocking, Antiadrenergic, and
Calcium blocking activity

6. Unique Mechanism of Action among
available class III drugs
Activation of a late
inward sodium current
Increased sodium influx
Shah D. Eur Heart J. 2016 May 21;37(20):1622-5.
Prolongation of the
myocardial action
potential duration.
+
-
V Max
plateau
Slow Na 
(Ibutilide)CaNa
N
T
QT
APD
Action Potential Duration
K+ (other class III)
Repolarization

7. No Hemodynamic Effects
No clinically significant Hemodynamic effect (at doses up to
0.03 mg/kg) demonstrated on
– Cardiac output,
– Mean pulmonary arterial pressure
– Capillary wedge pressure
Katherine T. Murray. Ibutilide. Circulation 1998;97;493-497.

8. Ibutilide: Electrophysiological
Effects
No clinically significant effect on QRS (at the recommended dosage)
A dose related prolongation of the QT interval
Prolongation of QT interval is similar in men & women
Prolongs action potential duration and effective refractory periods in both
atria and ventricles
Nair M. J Am Board Fam Med. 2011 Jan-Feb;24(1):86-92.

9. Pharmacokinetics
• Ibutilide is intravenously (i.v.)
administered
• Due to its high first-pass
metabolism, its not given orally
Katherine T. Murray. Ibutilide. Circulation 1998;97;493-497.
.http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
• The pharmacokinetics of Ibutilide
is similar regardless of
• The type of atrial arrhythmia,
• Age, sex
• Left ventricular ejection fraction,
• Occurrence of polymorphic
ventricular tachycardia
• The concomitant use of digoxin,
CCBs, or β-blockers.

10. After IV infusion, Ibutilide plasma concentrations rapidly decrease in a
multiexponential fashion.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
Pharmacokinetics

11. Indications
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
For the rapid conversion of
atrial fibrillation or atrial flutter
of recent onset to sinus rhythm.

12. Ibutilide: Dosage & Administration
Ibutilide infusion should be stopped as soon as the presenting arrhythmia is terminated
or in the event of sustained or nonsustained ventricular tachycardia, or marked
prolongation of QT or QTc.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf

13. Dilution
Solutions used
for dilution →
Ibutilide Injection 10 ml one Vial
+ 50 ml of 5 % Dextrose Injection
Ibutilide Injection 10 ml one Vial +
50 ml of 0.9 % NaCl Injection
Ibutilide Injection may be administered undiluted or diluted in 50 mL of diluent
Admixtures of the product, with approved diluents, are chemically and physically stable for 24
hours at room temperature (15°to 30°C )
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf

14. Clinical settings for Ibutilide usage
(cardioversion in AF and AFL)
1. Recent onset atrial fibrillation or flutter
2. Persistent atrial fibrillation or flutter
a) As standalone therapy
b) In patients already on oral amiodarone
c) To facilitate electrical cardioversion
d) To facilitate cardioversion of atrial flutter by overdrive atrial pacing
3. Post-operative atrial fibrillation or flutter
4. Pre-excited atrial fibrillation in patients with WPW syndrome
5. Atrial fibrillation or flutter during an electrophysiological study
or ablation procedure
6. Children and those with congenital heart disease
7. Elderly patients with atrial fibrillation or flutter
Kartikeya Bhargava. Role of Ibutilide in Atrial Fibrillation Supplement Issue on Atrial Fibrillation . JAPI • August 2016 • Vol. 64.

15. Contraindications
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
Patients with history of hypersensitivity to Ibutilide
fumarate or excipients in the formulation.

16. Warnings & Precautions
• Potential to prolong refractoriness When
given with Class Ia and other class III
antiarrhythmic, concomitantly or within 4
hours post infusion
• Class I and III agents may be withheld for at
least 5 half-lives prior to ibutilide infusion
• Potential for Proarrhythmia when given
with drugs that prolong the QT interval, such
as
– Phenothiazines,
– Tricyclic or Tetracyclic antidepressants
– Antihistamines- terfenadine, Astemizole
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
• Doses of more than two infusions are
not recommended in a single setting
due to the risk of QT prolongation
• Not recommended in
– Patients with QTc intervals > 440
msec.
– Patients with H/O polymorphic
ventricular tachycardias (e.g.,
torsades de pointes).
• More rapid infusion is not recommended.

17. Side Effects
Event Placebo (n=127) Ibutilide (n=586)
n % n %
CARDIOVASCULAR
Ventricular extrasystoles 1 0.8 30 5.1
Nonsustained monomorphic VT 1 0.8 29 4.9
Nonsustained polymorphic VT — — 16 2.7
Hypotension 2 1.6 12 2.0
Bundle branch block — — 11 1.9
Sustained polymorphic VT — — 10 1.7
AV block 1 0.8 9 1.5
Hypertension — — 7 1.2
QT segment prolonged — — 7 1.2
Bradycardia 1 0.8 7 1.2
Palpitation 1 0.8 6 1.0
Tachycardia 1 0.8 16 2.7
GASTROINTESTINAL
Nausea 1 0.8 11 1.9
CENTRAL NERVOUS SYSTEM
Headache 4 3.1 21 3.6

18. Common Non-arrhythmic Toxicity
of most frequently used anti-arrhythmic agents in AF/AFL
Ibutilide Nausea
Amiodarone Tremor, peripheral neuropathy, pulmonary inflammation,
hypothyroidism and hyperthyroidism, photosensitivity
Dofetilide Nausea
Propafenone Taste disturbance, dyspepsia, nausea, vomiting
Flecainide Dizziness, nausea, headache, decreased myocardial contractility
Sotalol Hypotension, bronchospasm
Harrison's Principles of Internal Medicine, 18th Ed. Chapter 233. The Tachyarrhythmias >

19. Pro-arrhythmic Manifestations
Amiodarone
Sinus bradycardia, AV block, increase in defibrillation threshold
Rare: long QT and torsades des pointes, 1:1 ventricular conduction with
atrial flutter
Ibutilide Long QT and torsades de pointes
Flecainide 1:1 Ventricular response to atrial flutter; increased risk of some ventricular
tachycardias in patients with structural heart disease; sinus bradycardia
Dofetilide Long QT and torsades des pointes
Propafenone 1:1 Ventricular response to atrial flutter; increased risk of some ventricular
tachycardias in patients with structural heart disease; sinus bradycardia
Sotalol Long QT and torsades des pointes, sinus bradycardia
Harrison's Principles of Internal Medicine, 18th Ed. Chapter 233. The Tachyarrhythmias

20. How to reduce Torsades de pointes
Pretreatment with Class IC drugs
Class IC drugs: Flecainide and Propafenone.
• Ibutilide effect is mediated through the delay of slow Na(+) current
inactivation.1
• Pretreatment with IC agents can reduce the increase in QTc seen with
Ibutilide2
• There is lower risk of Proarrhythmia since the class IC drugs induced
slow conduction by blocking sodium channels which exert somewhat
protective effect against Ibutilide toxicity.
• Ibutilide has been safely used in patients who are already on class IC
drugs.
1. Kartikeya Bhargava. Supplement Issue on Atrial Fibrillation . JAPI • August 2016 • Vol. 64. 2. Reiffel JA. J Cardiovasc Pharmacol Ther. 2000 Jul;5(3):177-81.

21. • Combined therapy of iv esmolol and Ibutilide vs.
Ibutilide alone in patients with recent onset AF showed
a higher rate of conversion to sinus rhythm (67% vs.
46%), reduced rate of immediate recurrence and a
lower risk of proarrhythmia1
• The addition of Esmolol reduces QTc prolongation and
diminishes the risk of ventricular tachycardia
• Magnesium prevents significant prolongation of QT interval
and therefore reduces the risks of torsade de pointes2
1. Fragakis N. Europace 2009; 11:70. 2. Wang A. Pharm Pract (Granada). 2012 Apr;10(2):65-71. 21
How to reduce Torsades de pointes
Ibutilide in combination with Esmolol or MgSO4

22. Predictor of successful cardioversion
with Ibutilide
1. Recent onset of arrhythmia
2. Atrial flutter rhythm
3. Relatively high heart rate
4. Lack of a H/O of CHF
5. Lack of concomitant digoxin therapy
6. Female gender and younger age
Zaqqa M. Am J Cardiol. 2000 Jan 1;85(1):112-4, A9.

23. Geriatric Use
• Usually start at the low end of the dosing
range, because of
– Decreased hepatic or renal function
– Decreased Cardiac function
– Concomitant disease or other drug therapy.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
• Clinical experience shows no difference in responses
between the elderly & younger patients.

24. Use in Patients with Hepatic or Renal
Dysfunction
• The safety, effectiveness & pharmacokinetics
of Ibutilide have not been established in
patients with hepatic or renal dysfunction.
• It is unlikely that dosing adjustments would be
necessary in patients with compromised renal
or hepatic function
• Patients with abnormal liver function should be
monitored for >4-hour period.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf

25. Recommendations

27. Recommendation from AHA/ACC/HRS
Guidelines 2014
Anti-arrhythmic
Drugs
Class of Recommendation in following Indications
Atrial Fibrillation/Flutter
Wolff Parkinson White
and
Pre-excitation
Syndrome
Post operative
Cardiac & Thoracic
Surgery induced AF
Ibutilide Class I Class I Class IIa
Amiodarone Class IIa Not recommended Not recommended
Flecainide
Class I (in Hospital)
Class IIa (outside hospital
with β-blocker)
Not recommended Not recommended
Dofetilide Class I Not recommended Not recommended
Propafenone
Class I (in Hospital)
Class IIa (outside hospital
with β-blocker)
Not recommended Not recommended
Class-I Recommendation:Benefit >>> Risk ;Procedure/treatment SHOULD be performed/administered
Class-II Recommendation: CLASS II a - Benefit >> Risk Additional studies with focused objectives needed ; IT IS REASONABLE to perform procedure/administer
treatment; CLASS II b -Benefit ≥ Risk ;Additional studies with broad objectives needed; additional registry data would be helpful Procedure/treatment MAY BE
CONSIDERED
Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol.2014;64(21):2246-2280.

28. 28
Ibutilide Use In Different
Clinical Settings

29. IBUTILIDE Rescue for failed Amiodarone therapy
S
N
Title N Drugs Primary Endpoint Results
1 Marcus G. Hennersdorf et
al. Conversion of recent
onset atrial fibrillation or
flutter with ibutilide after
amiodarone has failed.
Intensive Care Med. 2002
Jul;28(7):925-9.
26 Ibutilide (1 mg or, 2
mg i.v.) after
Amiodarone (150 mg
i.v.) failed in Persistent
arrhythmia
Conversion of
recent onset atrial
fibrillation or
flutter
after amiodarone
has failed.
Ibutilide led “Sinus
Rhythm” conversion in
81.5% of patients where
Amiodarone had failed
29

30. • 70 pts on longterm oral amiodarone for
cardioversion in “Afib” (57/70) or “Afl” (13/70)
• Patients administered 2 mg i.v. Ibutilide.
• 55 patients (79%) had structural heart
disease.
• Patients on amiodarone:153 days
• Patients with arrhythmia for 196 days
before cardioversion.
Kathy Glatter. Circulation. 2001;103:253-257.
Patients converted within 30 minutes of infusion.
AFib- 22 of 57 (39%) and
AFl -7 of 13 (54%)
only 1 episode of torsade de pointes occurred
Ibutilide Add-on to long term Oral Amiodarone
30

31. Ibutilide Vs. Amiodarone (i.v.) in AF & AFl
N= 152 (Ibutilide n=79, Amiodarone n= 73)
Duration of AF or Afl: 3-48 h
Conversion to SR
All patients
Ibutilide: 63 of 79 pts (80%)
Amiodarone: 42 of 73 pts (57%)
In AFL
Ibutilide: 20 of 23 pts (87%)
Amiodarone: 6 of 21 pts (29%)
In AF
Ibutilide:43 of 56 pts (77%)
Amiodarone: 36 of 52 pts (69%)
80%
57%
77%
69%
87%
29%
Ibutilide is more effective than amiodarone in converting recent-onset AF or AFl to Sinus Rhythm
Kafkas NV. Int J Cardiol. 2007 Jun 12;118(3):321-5. 31

32. Ibutilide: Shorter Arrhythmia Termination Time
Kafkas NV, Int J Cardiol. 2007 Jun 12;118(3):321-5.
Atrial Fibrillation
53.4 min
492 min
Atrial Flutter
28.4 min
762 min
32

33. Ibutilide vs. Propafenone
SN Title N Drugs Primary
Endpoint
Results
1 Zhang HC et al. Immediate
cardioversion of atrial fibrillation and
atrial flutter lasting less than 90 days
by ibutilide versus propafenone: a
multicentre study. Zhonghua Yi
Xue Za Zhi. 2005 Mar
30;85(12):798-801.
212 Ibutilide (1 mg)
(n = 107), 75 AF & 32 AFL
Propafenone
(70 mg)
(n = 105, 76 AF & 29 AFL
IV over 10 mins
Cardioversion AFL conversion rate
Ibutilide = 78.1%
Propafenone 48.3%
33

34. Ibutilide vs. Propafenone
 Ibutilide 1 mg or Propafenone 70 mg
[2 infusions, 10 min apart]
 N= 82 pts with AF
 Onset : 2 h to 90 days
 The treatment was considered successful if sinus rhythm occurred within 90 mins
p = 0.043
Zhang N. Int J Clin Pract. 2005 Dec;59(12):1395-400.
Ibutilide is more effective than intravenous propafenone for the cardioversion
34

35. Sun JL. Cardiovasc Drugs Ther. 2005 Jan;19(1):57-64.
Ibutilide was superior to propafenone for treating atrial flutter (90% vs. 30%).
n=40
Ibutilide-20
Propafenone-20
Bradycardia &
hypotension were more
common side effects with
propafenone.
Randomized to receive
Ibutilide 1 mg
 Propafenone 70mg
Ibutilide vs. Propafenone
35

36. Ibutilide with Propafenone
3 John A. Chiladaki et al.
Ibutilide added to
propafenone for the
conversion of atrial
fibrillation and atrial
flutter. J Am Coll
Cardiol. 2004 Aug
18;44(4):859-63.
202 Oral propafenone
N=202
With AF/AFL without left
ventricular dysfunction.
IV Ibutilide (1mg)
N=104
(48 pts with paroxysmal
arrhythmia, & 56 with
chronic arrhythmia)
Safety &
efficacy of
Ibutilide when
added to
propafenone
Ibutilide offered an overall
conversion efficacy of 66.3%.
•70.8% for patients with
paroxysmal AF/AFL
•62.5% for patients with chronic
AF/AFL.
36

37. Ibutilide 2mg
Cardioversion of pts on Class IC Agents
• Total 71 pts. AF (n=48) & AFL (n= 23)
• Pts. on Propafenone 300 to 900 mg/day (n=46) or Flecainide 100 to 300
mg/day (n= 25)
Conversion rates:
AF - 23 of 48 pts (47.9%)
AFL- 17 of 23 pts (73.9%)
No pts needed to stop of Ibutilide infusion
for ventricular dysrhythmia or excessive QT
prolongation.
Attenuation of Ibutilide-induced QTC prolongation:
 Class IC agents block slow inward INa in addition to fast INa
 In this study mean Ibutilide-induced QTC interval prolongation was 20
ms as compared to 47 to 90ms (reported in literature)
 This attenuation is without decrease in Ibutilide efficacy
Hongo RH. J Am Coll Cardiol. 2004 Aug 18;44(4):864-8.
37

38. Ibutilide Vs. Procainamide
ADVERSE EVENTS :
More common with procainamide (46.2%) than with Ibutilide group -29.0%
Ibutilide - Extrasystole occurred .
Procainamide - Headache, hypotension, flushing, dizziness and hypesthesia
Volgman AS. J Am Coll Cardiol. 1998 May;31(6):1414-9.
Combined Conversion rates
Ibutilide –58%
Procainamide - 18%
Atrial Flutter
Ibutilide -76%
Procainamide -14%
Atrial Fibrillation
Ibutilide - 51%
Procainamide -21%
Study Establishes The Superior Efficacy Of Ibutilide Over Procainamide
Total N= 120 , Ibutilide n=60 procainamide n=60
38

39. Randomized, double-blinded comparative study- 136 patients treated :
• i.v. Ibutilide (n=73)
•placebo (n=22)
•iv procainamide (n=53)
Bruce S. Stambler et al. Circulation. 1997;96:4298-4306
Ibutilide Vs. Procainamide
In AFL
Ibutilide converted 29 of 45 pts= 64%
Procainamide & placebo converted 0%
In AF
Ibutilide converted 9 of 28 pts 32%
Procainamide converted in 1 of 20 5%
Placebo converted 0%
39

40. Ibutilide vs. Procainamide
S
N
Title N Drugs Primary
Endpoint
Results
3 Stambler BS et al.;
Comparative efficacy of iv
Ibutilide versus procainamide for
enhancing termination of atrial
flutter by atrial overdrive pacing
Am J Cardiol. 1996 May
1;77(11):960-6.
54 Ibutilide n=15 or
Procainamide
n=33 or
Placebo n =11
Termination
of atrial
flutter
Pacing converted SR
18% placebo, 87%
ibutilide, (88%)
procainamide
40

41. Ibutilide vs. Sotalol
Vos M. et al. Heart. 1998;79(6):568-575.]
• Ibutilide (given in 1 or 2 mg doses over 10 mins Rapidly terminates persistent AF
or AFL.
• Ibutilide (2 mg) was superior to Sotalol in both atrial flutter and fibrillation
• Ibutilide vs Sotalol in Atrial flutter (70% vs. 19%),
• Ibutilide vs Sotalol in Atrial Fibrillation (44% v 11%)
Double blind, randomised
study.
308 patients with atrial
fibrillation (n = 251) or atrial
flutter (n = 57)
(duration 3 hrs to 45 days) .
three groups :
1 mg ibutilide (n = 99)
2 mg ibutilide (n = 106)
1.5 mg/kg DL-sotalol (n = 103)
41

42. Magnesium as an adjunct to Ibutilide,
improves efficacy & minimize toxicity
1. Magnesium have intrinsic
antiarrhythmic properties
2. Potential to increase the
efficacy of class III
antiarrhythmics
3. Delays AV node conduction,
without significant effect on
the sinus node
3. Efficacy of magnesium &
Ibutilide combination is due
to the additive potassium
blockade effect
4. Side effects of magnesium
are usually mild : e.g. minor
tingling, flushing & dizziness
Wang A. Pharm Pract (Granada). 2012 Apr;10(2):65-71.
42

43. Magnesium as an adjunct for Ibutilide…..
• Therefore, magnesium with Ibutilide involves
minimal risks with monitoring of vital signs &
ECG.
• Magnesium prevents significant prolongation
of QT interval and therefore reduces the risks
of torsade de pointes
The administration of magnesium makes Ibutilide a much safer
agent, & magnesium increased the conversion efficacy of Ibutilide
Wang A. Pharm Pract (Granada). 2012 Apr;10(2):65-71.
4 g of magnesium may be given within 2 hrs prior to initiation of
Ibutilide for conversion of AF or typical flutter
43

44. Ibutilide and Magnesium Combination
Therapy
Article Study
Design
Groups Doses of magnesium
used
Rates of Successful
Cardioversion
Kalus JS. Am J
Health Syst
Pharm. 2003 Nov
15;60(22):2308-
12.
Retrospective
, cohort
N = 321
1. Control: Ibutilide
alone
N = 214
2. Treatment:
Ibutilide & MgSO4
N = 107
Mean total dose: 2.2 + 1
grams Magnesium was
given within 2 hours
before or during ibutilide
therapy
Treatment group: 72%
Control group: 60.3%
p = 0.04
Patsilinakos S.
Am J
Cardiol. 2010 Sep
1;106(5):673-6.
Prospective
N = 476
1) Ibutilide alone
N = 229
2] Ibutilide & MgSO4
N = 247
5 grams given 1 hour
prior to first dose of
Ibutilide, followed by
another 5 grams given
over 2 hours
Treatment group: 76.5%
Control group: 67.3%
p = 0.033
Steinwender C.
Int J Cardiol. 2010
Jun
11;141(3):260-5.
Randomized,
placebo
controlled
N = 117
1. Ibutilide and
placebo
N = 59
2. Ibutilide & MgSO4
N = 58
Magnesium 4 grams or
placebo given 20
minutes prior to first
dose of ibutilide
Treatment group (typical
AF): 85%
Control group (typical
AF): 59%
p = 0.017
Tercius AJ.
Pacing Clin
Electrophysiol 2007
Nov;30(11):1331-5.
Retrospective
cohort
N = 229
1. Ibutilide only
N = 88
2. Ibutilide & MgSO4
N = 141
Magnesium 1-4 grams
within 2 hours prior to
ibutilide
78% more chances of
conversion with
combination versus
59.8% without MgSO4
44

45. 1
Stavros E. Et al.
Ibutilide to expedite ED
therapy for recent-onset
atrial fibrillation flutter
Am J Emerg Med.2006
Jul;24(4):407-12.
Total = 36
(AFib = 26)
&
(AFl = 10)
Ibutilide 1 mg
Successful
conversion
within 1 hour
90% patients with AFl and
61.5% patients with AFib
converted to sinus rhythm
No significant complications
occurred.
2
Amy Eversole.et al.
Ibutilide: Efficacy and Safety
in Atrial Fibrillation and Atrial
Flutter in a General
Cardiology Practice. Clin.
Cardiol. 2001;24,521-
525
Total = 54
Afib (n=34)
Afl (n= 20)
Ibutilide
1 mg for pts ≥
60 kg & 0.1
mg/kg for pts
< 60 kg
Successful
cardioversion
70.6% pts with AFib & 75%
with AFl converted to SR.
Conversion of AFib to SR
more likely if duration of AFib
= 96 h versus >96 h (81 %
vs. 17%).
3
Gowda RM.et al. Use
of ibutilide for cardioversion of
recent-onset atrial fibrillation and
flutter in elderly.
Am J Ther. 2004 Mar-
Apr;11(2):95-7.
Total = 32
AFib n=19
AFl n =13
Ibutilide 1 mg Cardioversion
Successful Arrhythmia
Termination = 59%.
63% in patients with AFib &
54% in AFl
The mean conversion time was
33 +/- 45 minutes.
Efficacy of Ibutilide
45

46. 44 patients (75%) converted to SR after Ibutilide
31 on single dose (53%) & 13 on double dose (22%)
Ibutilide in AFL- Single vs Double Dose
Andò G. Minerva Cardioangiol. 2004 Feb;52(1):37-42.
The mean time to the 2nd dose was
34 min in responders
46
N= 59 patients
dose- 1 mg Ibutilide.

47. • 266 pts with AF (n = 133) or flutter (n = 133),
• Arrhythmia duration - 3 hrs to 45 days
• Randomized to receive up to two 10-min infusions of
– Ibutilide (1.0 and 0.5 mg) or
– Ibutilide (1.0 and 1.0 mg)
– Placebo
• The conversion rate
– 47% after Ibutilide &
– 2% after placebo
• Efficacy was higher in AFl than fibrillation (63% versus 31%)
• Arrhythmia termination - 27 min after start of the infusion
• Of 180 Ibutilide-treated patients, 15 (8.3%) developed polymorphic ventricular
tachycardia during or soon after the infusion
Efficacy and safety of Repeated I.V. doses of
Ibutilide
Ibutilide given in repeated doses is effective in rapidly terminating
AF & AFl
Stambler B et al. Circulation 1996;94:1613-1621. 47

48. Ibutilide Vs. Placebo
SN Title N
Drugs Primary
Endpoints Results & conclusion
1
Abi-Mansour P.et al. Am
Heart J. 1998 Oct;136(4
Pt 1):632-42.
n=250 Ibutilide 1 mg
(n=209)
or
Placebo
(n=41)
Termination of
atrial fibrillation
or flutter
34.9% of ibutilide Pts had
cardioversion within 1.5 hrs
0% of placebo Pts
At 24 Hrs, 86.3% of Ibutilide
recipients remained in SR
2
James T. VanderLugt.et al.
Efficacy and Safety of Ibutilide
Fumarate for the Conversion of
Atrial Arrhythmias After Cardiac
Surgery. Circulation.
1999;100: 369-375.
n = 302
AFib=20
1
AFl=101
Ibutilide (n= 218)
(0.25, 0.5, or 1.0 mg)
or
Placebo (n=84)
Conversion
within 90 mins
Conversion rates = Placebo 15%;
Ibutilide 0.25 mg 40%, 0.5 mg 47%,
and 1.0 mg 57%
Mean time to conversion decreased
as the Ibutilide dose was increased
48

49. Ibutilide in different conditions &
procedures

50. Pretreatment with Ibutilide facilitate
Electrical cardioversion
• It increases the conversion rate1
• Reduces the energy required to cardiovert2
• Reduces the number of attempts at cardioversion1
• Successful cardioversion in patients who failed initial
shock without Ibutilide pretreatment1
• 100% with Ibutilide versus 72 % without Ibutilide
1. Oral H. N Engl J Med 1999; 340:1849–54.
2. Mazzocca G. J Cardiovasc Med 2006; 7:124–8.

51. Ibutilide 1 mg with electrical cardioversion
51
n =100
Transthoracic cardioversion
with or without pre-
treatment
Pretreatment reduced mean
energy required for
defibrillation (166 J vs. 228 J
without pretreatment)
Oral H. N Engl J Med. 1999 Jun 17;340(24):1849-54.

52. Ibutilide for conversion after Cardiac Surgery
Ibutilide: Higher conversion rates than placebo, efficacy was dose related
Polymorphic ventricular tachycardia - in Ibutilide group 1.8% vs. 1.2% in placebo group
N= 302, Fibrillation- 201, flutter- 101
Ibutilide is a safe treatment alternative for Post cardiac surgery Atrial Arrhythmias
VanderLugt JT. Circulation. 1999 Jul 27;100(4):369-75.
52

53. Ibutilide in children & patients with
Congenital Heart Disease
RESULTS:
– 74 episodes of AFl and 4 episodes of AF
(median episodes / patient was 1, range
1-31).
– Ibutilide converted 55 of all the
episodes (71%).
– Success during its first-ever
administration in 12 of 19 patients: 63%.
– One patient went into torsade de pointes.
Hoyer AW. Pacing Clin Electrophysiol. 2007 Aug;30(8):1003-8.
19 patients (age 6 mths to 34 years) who received Ibutilide between 1996-2005
15 patients with CHD (14 had prior heart surgery); 4 children had normal heart
structure.
Ibutilide - effective in selected paedo pts for cardioversion of AFL
53

54. • Ibutilide successfully terminated AF in 95% of
patients (including children) during
electrophysiology study of accessory pathways
that were subsequently ablated. 1
• Ibutilide an alternative to Procainamide for
cardioversion in stable pts with preexcited AF.2
Ibutilide in Preexcited AF in WPW Syndrome
1. Glatter KA. Circulation. 2001 Oct 16;104(16):1933-9. 2. Varriale P. Pacing Clin Electrophysiol. 1999 Aug;22(8):1267-9.
54

55. Ibutilide Enhances Termination of AFl by
Burst Atrial Overdrive Pacing
• 26 patients for “pacing termination” with standard
protocol of “Burst Atrial Overdrive Pacing”
• Ibutilide enhanced pacing-induced termination of
AFl compared to placebo (p <0.001) .
• PACING CONVERSION:
– 2 of 11 patients (18%) on placebo
– 13 of 15 patients (87%) on Ibutilide.
Stambler BS. Am J Cardiol. 1996 May 1;77(11):960-6.
55

56. n=87 (AFL duration 2 hr to 30 days)
randomized :
Group 1—i.v. Ibutilide treatment, up to 2 mg
Group 2—ATP with “burst” and “ramp” pacing
protocols
Andrea Mazza et al. Europace 2004;6:301-30656
Ibutilide vs. Transoesophageal Atrial Pacing

57. Andrea Mazza et al. Europace 2004;6:301-306
Group 1:
i.v. ibutilide
Group 2:
Transoesophageal atrial
pacing
Rate of sinus rhythm restoration
Ibutilide appears to be the best choice in AFL
Ibutilide vs. Transoesophageal Atrial Pacing

58. Ibutilide after Radiofrequency Ablation
58

59. Ibutilide after Radiofrequency Ablation
SN Title N
Drugs Primary
Endpoints
Results & conclusion
1
Tian XC.et al. Efficacy
of ibutilide for cardioversion
of persistent Afib during
radiofrequency ablation.
Zhonghua Xin Xue Guan
Bing Za Zhi. 2011 Nov;
39(11):1029-32.
AFib
(n = 18)
Pts treated with 1 mg
Ibutilide within 10
minutes after
unsuccessful ablation
Cardioversion Ibutilide is highly effective and safe
for cardioversion in pts where
ablation failed.
After Ibutilide administration
61.11% converted to SR.
The average conversion time was
13.80 min.
2
Hou Yu.et al. Single dose
of ibutilide for conversion
of persistent Atrial
fibrillation after
radiofrequency ablation.
Chin Med J (Engl). 2011
Mar;124(5):710-713
AFib
(n = 40)
Pts whose AFib was
not converted to
sinus rhythm after
radiofrequency
ablation were given
1mg Ibutilide.
Rate of
conversion
Ibutilide converted 72.5% patients
to sinus rhythm.
Mean conversion time = 13 mins.
No cases of serious arrhythmias or
other adverse reactions were
found.
59

60. The Modified Ablation Guided by Ibutilide Use in
Chronic Atrial Fibrillation (MAGIC-AF) Study
• International multicenter RCT
• Assessed the utility of the intraprocedural
administration of 0.25 mg of
iv Ibutilide before performing Complex
fractionated atrial electrograms (CFAE)
ablation
Singh SM. Eur Heart J. 2016 May 21;37(20):1614-21.
200 pts undergoing a first-ever persistent AF catheter ablation procedure
were randomly assigned to receive either
0.25 mg of iv Ibutilide or
saline placebo
CFAE sites were then targeted with ablation. 60

61. MAGIC-AF Study continued……
When CFAE ablation was guided by Ibutilide
administration it results into
– Reduction in CFAE area and
– Greater AF termination (75 vs. 57%)
Singh SM. Eur Heart J. 2016 May 21;37(20):1614-21.
61

62. Ibutilide for AF and flutter in cancer pts.
RESULTS:
• Successful cardioversion in 75% of
patients
• 68 patients (84%) were on at least 1
medication that prolonged the QT interval at
the time of Ibutilide administration
• No significant changes in the corrected QT
interval post Ibutilide cardioversion
Bickford CL. Am J Med Sci. 2014 Apr;347(4):277-81.
Centre: University of Texas MD Anderson Cancer Center
81 patients received Ibutilide for AF/AFL from January 2002 to May 2006
Ibutilide is safe and effective in cancer pts.
Despite the use of multiple drugs that can potentially prolong the QT interval,
no patient experienced serious rhythm disturbances or significant QT
prolongation during Ibutilide administration
62

63. Ibutilide in CAD (Coronary Artery Disease)
MVD (Mitral Valve Disease) and LAH (Left Atrial Hypertrophy)
The response rate in patients with CAD was higher than in patients without CAD
(23/30= 77%, vs. 33/71= 46%)
Das MK. Clin Cardiol. 2002 Sep;25(9):411-5.
n=101
63

64. Continued……..
Ibutilide success rate:
Presence of MVD- 37.7% (23/61 pts)
Absence of MVD- 82.5% (33/40 pts)
(p <0.01)
Ibutilide Response rate:
85% (29 of 34 ) in pts without MVD &
without markedly enlarged LA
Ibutilide is most effective in patients with CAD or in patients without MVD and/or without
markedly enlarged LA
Das MK. Clin Cardiol. 2002 Sep;25(9):411-5.
64

65. Fibricor Summary
1. Ibutilide is Pure class III antiarrhythmic drug for AFL and AF
2. Quick onset of action (with in minutes)
3. Best in class III antiarrythmics
4. Easy and rapid administration
5. Low incidence of adverse effects
6. A good alternative to electrical cardioversion
7. Ibutilide Pretreatment increases electrical conversion from 72% to 100%
8. Can be used safely in AF/ AFL patients receiving oral amiodarone
9. Accessory pathway-mediated AF- the conversion rate of Ibutilide is 95%.
10.Safe and effective in post-cardiac surgery AF patients
11.Risk of torsades de pointes (TDP)- up to 4%
12.Proarrhythmia prevented by Class IC drugs (Flecainide & Propafenone)
or IV Esmolol or Mg SO4
13.Monitor at least for 4 hrs or until QTc has returned to baseline
14.The anticoagulation strategy is the same as for any other mode of
cardioversion
65

66. Thank
you !