Amiodarone is a complex antiarrhythmic drug used for treating life-threatening ventricular arrhythmias and atrial fibrillation. It has a long half-life of 58 days and can cause various adverse effects if used long-term at higher doses, including pulmonary toxicity, thyroid abnormalities, skin discoloration, and interactions with other drugs. Patients on amiodarone require regular monitoring for efficacy and side effects, especially monitoring of thyroid function every 3-6 months due to risks of hypothyroidism and hyperthyroidism.

1. Amiodarone
Drug Of The Month
Presenter
Praveen upta
Moderator
Santhosh Satheesh
Head of Department,
Department of Cardiology,
JIPMER
Pondicherry, India
Date
26-04-2016
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2. Amiodarone
Introduction
 Complex antiarrhythmic agent
 Benzofuran derivative
 Labeled only for life threatening VT
 Iodine-containing compound
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3. Clinical Pharmacology
Pharmacokinetics
 Bioavailability- 22 to 95 percent.
 Absorption is enhanced with food
 Lipid soluble and is stored in high concentrations in fat and muscle, liver,
lungs, & skin
 Routine monitoring of plasma level not recommended.
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4. Clinical Pharmacology
Pharmacokinetics
 Plasma peak concentrations, 3 to 7 hours after single oral dose.
 Minimal first-pass effect
 Elimination by hepatic excretion
 Extensive hepatic metabolism with desethylamiodarone as a metabolite.
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5. Clinical Pharmacology
Pharmacokinetics
 Myocardium concentration 10 to 50 times of plasma
 Plasma clearance is low, and
 Renal excretion is negligible
 Doses modification not requried in renal disease.
 Amiodarone and desethylamiodarone not dialyzable
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6. Clinical pharmacology
Pharmacokinetics
 Large Volume of distribution (60 liter/kg)
 Highly protein bound (96%)
 Crosses the placenta
 Measurable levels in breast milk
 desethylamiodarone have antiarrhythmic properties
 Elimination half-life is 58 days
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7. Electrophysiologic effects
 Class III drug
 Prolongs the QT interval
 Slows heart rate and
atrioventricular nodal
conduction
 Prolongs refractoriness (via
potassium and sodium channel
blockade)
 Slows intracardiac conduction
(via sodium channel blockade).
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8. Indications
Long-term treatment
 Secondary prevention of life-threatening VT.
 For patients who have survived sustained VT & with left ventricular
dysfunction
 For primary prevention of SCD
 As an adjunct to reduce the frequency of ICD shocks
 Treatment of atrial fibrillation, although the FDA has not approved this
indication.
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9. Indications
Long-term treatment
 Hypertrophic cardiomyopathy
 Nonischemic dilated cardiomyopathy
 Asymptomatic ventricular arrhythmias after myocardial infarction
 Ventricular tachyarrhythmia during and after resuscitation from cardiac
arrest
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10. Acute treatment
 IV amiodarone for the emergency treatment of VT
 Onset of action with IV therapy in less than 30 minutes
 ACLS recommended for the initial treatment of hemodynamically stable
wide-complex tachycardia
 In patients who require long-term treatment, intravenous dosing should be
switched to oral dosing
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11. Acute treatment
 Hemodynamically unstable atrial fibrillation
 AF with rapid ventricular rates
 AF with impaired renal function
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12. Amiodarone indication
 Junctional tachycardia
 AV node /AV entry
 Before open heart surgery as well as postoperatively to decrease the
postoperative atrial fibrillation
 60% to 80% effective for supraventricular tachyarrhythmias
 40% to 60% for ventricular tachyarrhythmias
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13. Dosage of amiodarone
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14. Amiodarone in stable monomorphic VT
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15. Role of Amiodarone in cardiac arrest
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16. Amiodarone in AF
Proposed treatment algorithm for the use of dronedarone in the therapy of patients with atrial fibrillation.
Atrial fibrillation: Dronedarone and amiodarone—the safety versus efficacy debate
Eric N. Prystowsky, Nature Reviews Cardiology 7, 5-6 (January 2010) doi:10.1038/nrcardio.2009.221
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17. Adverse Effects
 75% of patients over 5 years
 Compel stopping of the drug in 18% to 37%
 Most frequent ,Pulmonary and gastrointestinal
 Reversible with dose reduction or cessation of treatment
 Common when therapy is long term and at higher doses
 Pulmonary toxicity, most serious
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19. Amiodarone effect on thyroid gland
 Inhibit the peripheral conversion of T4 to T3
 Slight increase in T4, reverse T3, and thyroid-stimulating hormone (TSH)
and a slight decrease in T3 levels
 Reverse T3 concentration, used as an index of drug efficacy
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20. Amiodarone effect on thyroid gland
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21. Amiodarone effect on thyroid gland
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22. Amiodarone induced thyrotoxicosis
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Approach to the Patient with Amiodarone- Induced Thyrotoxicosis
Fausto Bogazzi, Luigi Bartalena, and Enio Martino
Department of Endocrinology (F.B., E.M.), University of Pisa, 56124 Pisa, Italy; and
Department of Clinical Medicine (L.B.), University of Insubria, 21100 Varese, Italy
J Clin Endocrinol Metab, June 2010, 95(6):2529–2535 jcem.endojournals.org

23. Amiodarone-Induced Hypothyroidism
(AIH)
 More than amiodarone induced thyrotoxicosis (AIT) in iodine-sufficient
Areas
 More in females
 Patients are older than AIT
 AIH usually develops earlier than AIT
 Presence of anti-thyroid peroxidase (TPO) antibodies is risk AIH
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24. Amiodarone-Induced Hypothyroidism
(AIH)
 Baseline elevation of TSH risk factor for AIH
 Thyroid gland with Hashimoto’s thyroiditis, unable to escape from the acute Wolff-
Chaikoff effect after an iodine load and to resume normal thyroid hormone
synthesis
 Patients without underlying thyroid abnormalities and with negative thyroid
autoantibody tests, subtle defects in iodine organification and thyroid hormone
synthesis are likely cause AIH
 May spontaneously remit after discontinuation of amiodarone
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25. Monitoring of thyroid function for patient on
amiodarone
 Thyroid function tests, every 3 months for first year
 Once or twice yearly, thereafter
 Sooner ,if symptoms develop, that are consistent with thyroid dysfunction
 During hypothyroidism, the TSH level increases greatly
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26. Amiodarone effect on thyroid gland
Algorithm for management of amiodarone-induced thyroid disease. Amiodarone-induced thyroid disease can be diagnosed based
on classic signs and symptoms of either hypothyroidism or hyperthyroidism or, more commonly, by routine (every 3-6 months)
thyroid function testing. Any single abnormal TSH concentration (>10 mIU/l), an indication of clinical hypothyroidism (AIH),
should be confirmed and treated with levothyroxine. AIT management depends upon the severity and duration of clinical signs or
symptoms. Mixed type 1 and type 2 AIT may require combination therapy with thionamides and corticoid steroids. Abbreviations:
AIH, amiodarone-induced hypothyroidism; AIT, amiodarone-induced thyrotoxicosis.
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Effects of Amiodarone Therapy on Thyroid Function: Amiodarone-related Adverse Effects Janna Cohen-Lehman,
DO; Peter Dahl, MD; Sara Danzi, PhD; Irwin Klein, MD Faculty and DisclosuresCME Released: 11/24/2009; Valid
for credit through 11/24/2010, Medsccap, Saturday, October 15, 2016

27. Pulmonary toxicity
 Frequency - 2 to 17%
 Result from direct drug-induced phospholipidosis or immune-mediated
hypersensitivity
 Subacute cough
 Progressive dyspnea
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28. Pulmonary toxicity
 ARDS-Can develop rapidly
 Worsening dyspnea or cough, do prompt assessment
 Congestive heart failure can mimic amiodarone pneumonitis and, must be
ruled out early in the evaluation
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29. Amiodarone induced pulmonary fibrosis
 Patchy interstitial infiltrates on
chest radiographs
 Reduced DLCO
 HRCT chest
 Lower incidence if dose 300
mg/day or less
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Amiodarone lung, A.Prof Frank
Gaillard◉ et al

30. Pulmonary toxicity
treatment
 Withdrawal of amiodarone
 Supportive care
 Corticosteroids
 Toxicity is reversible
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31. Cardiovascular adverse effects
 Bradycardia and heart block occur in 1 to 3 %
 Proarrhythmia occurs in less than 1 %
 Prolongation of the QT interval
 Polymorphic ventricular tachycardia (i.e., torsades de pointes) is rare
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32. Cardiovascular adverse effects
 CI in patients with second- or third-degree heart block
 IV amiodarone-heart block or bradycardia in 4.9%
 Hypotension in 16 %
 Infusion discontinued, or rate reduced, if patient develop complication
 Phlebitis (Use central venous line when possible)
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33. Adverse effect of amiodarone
 Corneal microdeposits
 Occur in 100% of adults receiving
the drug longer than 6 months
 Optic neuritis (Rare)
 Optic atrophy (Rare)
 Visual loss (Rare)
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Amiodarone-Induced Vortex
Keratopathy,Tommy C.Y. Chan, M.B.,
B.S.Vishal Jhanji, M.D., N Engl J Med 2015;
372:1656April 23, 2015DOI:
10.1056/NEJMicm1406501

34. Amiodarone induced skin discoloration
 Photosensitivity
 Less frequently
phototoxicity
 Blue–gray skin
 Hyperpigmentation of
sunexposed areas
 <10% of patients
 Preferentially men
Q J Med 2011; 104:723–724, doi:10.1093/qjmed/hcq131,
Advance Access Publication 30 July 2010

35. Amiodarone induced skin discoloration
 20 months of continuous treatment and a minimal cumulative dose of
160 g
 Due to lysosomal dermal lipofuscin deposits
 Treatment is reduction or cessation of therapy
 Skin changes slowly abate
 Skin discoloration persist for years
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36. Drug Interactions
 Potent inhibitor of the hepatic and renal metabolism of several drugs
 Inhibits metabolism through several cytochrome P450 pathways
 CYP 2C9 ( warfarin )
 CYP 2D6 ( beta blockers and narcotics)
 CYP 3A4 (cyclosporine/CCB)
 Interactions with digoxin
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38. Monitoring of Amiodarone
 Followed regularly
 Assess ongoing need
 Efficacy of the drug
 Appropriateness of dosage
 Adverse effects
 Potential drug interactions
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41. Take home message
 Effective in patient with AF both short and long term use
 Effective in patient with acute VT
 Not effective in prevention of SCD in primary and secondary prevention trial
 Helpful in prevention of no of ICD shock
 Followed patient regularly
 See for adverse effects
 Look for potential drug interactions
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42. Reference
 Amiodarone: Guidelines,for Use and Monitoring, LYLE A. SIDDOWAY,
M.D., York Hospital, York, Pennsylvania, December 1, 2003 / Volume 68,
Number 11 www.aafp.org/afp, American Family Physician
 Images- Google image
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43. Thank you
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