amiodarone, drug of the month

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Amiodarone Drug Of The Month

Presenter

Praveen upta

Moderator

Santhosh Satheesh

Head of Department,Department of Cardiology,

JIPMERPondicherry, India

Date26-04-2016

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AmiodaroneIntroduction

Complex antiarrhythmic agent

Benzofuran derivative

Labeled only for life threatening VT

Iodine-containing compound

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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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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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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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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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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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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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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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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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Acute treatment

Hemodynamically unstable atrial fibrillation

AF with rapid ventricular rates

AF with impaired renal function

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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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Dosage of amiodarone

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Amiodarone in stable monomorphic VT

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Role of Amiodarone in cardiac arrest

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Amiodarone in AFProposed treatment algorithm for the use of dronedarone in the therapy of patients with atrial fibrillation.

Atrial fibrillation: Dronedarone and amiodarone—the safety versus efficacy debateEric N. Prystowsky, Nature Reviews Cardiology 7, 5-6 (January 2010) doi:10.1038/nrcardio.2009.221

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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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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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Amiodarone effect on thyroid gland

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Amiodarone effect on thyroid gland

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Amiodarone induced thyrotoxicosis

Approach to the Patient with Amiodarone- Induced ThyrotoxicosisFausto 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, ItalyJ Clin Endocrinol Metab, June 2010, 95(6):2529–2535 jcem.endojournals.org

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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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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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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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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.

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

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Pulmonary toxicity

Frequency - 2 to 17%

Result from direct drug-induced phospholipidosis or immune-mediated

hypersensitivity

Subacute cough

Progressive dyspnea

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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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Amiodarone induced pulmonary fibrosis

Patchy interstitial infiltrates on

chest radiographs

Reduced DLCO

HRCT chest

Lower incidence if dose 300

mg/day or less

Amiodarone lung, A.Prof Frank Gaillard  et al◉

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Pulmonary toxicity

treatment

Withdrawal of amiodarone

Supportive care

Corticosteroids

Toxicity is reversible

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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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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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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)

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

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

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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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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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Monitoring of Amiodarone

Followed regularly

Assess ongoing need

Efficacy of the drug

Appropriateness of dosage

Adverse effects

Potential drug interactions

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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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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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Thank you