Pharm
Amiodarone
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Amiodarone
, Cordarone
See Also
Amiodarone Pulmonary Toxicity
Indications
Ventricular
Arrhythmia
s
Stable
Wide Complex Tachycardia
Stable
Ventricular Tachycardia
Pulseless Ventricular Tachycardia
Pulse
less
Ventricular Fibrillation
Supraventricular
Arrhythmia
s
Supraventricular Tachycardia
Ventricular rate control
Rapid atrial
Arrhythmia
s (
Atrial Fibrillation
)
Accessory pathway (
Wolff-Parkinson-White Syndrome
)
Atrial Fibrillation Cardioversion
Time to Cardioversion: 8-24 hours
Conversion Rate: 43-68%
Chronic Efficacy: 55-65%
Precautions
Hepatocellular necrosis risk (FDA black box warning)
Amiodarone Pulmonary Toxicity
risk (FDA black box warning)
Drug Interaction
s and adverse effects persist for weeks after stopping Amiodarone (60 day half-life)
Mechanism
Class IA
Antiarrhythmic
High affinity for inactive
Sodium
channels
Most effective in tissue with long
Action Potential
s
Class II
Antiarrhythmic
Non-competitive
Beta-Blocker
Class III
Antiarrhythmic
Prolongs refractory period via
Action Potential
Class IV
Antiarrhythmic
Weak
Calcium Channel Blocker
Pharmacokinetics
Half life: 60 days (range 13 to 103 days)
Effective plasma concentration: 1-2 ug/ml
Effects
Gene
ral cardiac effects
Inhibits abnormal automaticity
Increases refractory period in all conduction system
Anti-
Angina
l effects
Atrial effects
Slows sinus node rate
Slows
Atrioventricular Node
conduction
Ventricular effects
Prolongs
QT Interval
Prolongs
QRS Duration
slightly
Non-cardiac effects
Peripheral vascular dilatation
Adverse Effects
Precautions
More than half of patients experience adverse effects
Mnemonic for toxicity
PFTs (
Pulmonary Function Test
s)
TFTs (
Thyroid Function Test
s)
LFTs (
Liver Function Test
s)
Cardiac
Symptomatic Bradycardia
Heart Block
Hypotension
(Pressure support often required)
Congestive Heart Failure
exacerbation
Proarrhthmia effect (2-5%)
Eye
Optic Neuritis
Cornea
l deposits (90%)
Yellow-brown microcrystal deposits in
Cornea
Deposits appear within weeks of treatment
May interfere with vision in 10% of cases
Halos in peripheral
Visual Field
s (night-time)
Visual Acuity
rarely decreased
Skin Deposits
Photodermatitis
(25%)
Grayish-blue
Skin Discoloration
(5-9%)
Neurologic
Paresthesia
s
Tremor
Ataxia
Headache
Endocrine
Amiodarone resembles T4 and T3 hormone and may cause either
Hypothyroidism
or
Hyperthyroidism
Hypothyroidism
(6%)
Amiodarone may cause
Myxedema Coma
with elevated TSH (but normal or high T4 and T3)
Hyperthyroidism
(2%)
Fatigue
Gastrointestinal
Constipation
(20%)
Hepatocellular necrosis
Pulmonary
Amiodarone Pulmonary Toxicity
(diffuse pneumonitis)
Pulmonary fibrosis (in up to 17%)
Drug Interactions
Decreased
Heart Rate
and
AV Node
Conduction
Beta Blocker
s
Calcium Channel Blocker
s
QT Prolongation
with proarrhythmia risk
Fluoroquinolone
s (e.g.
Ciprofloxacin
)
Macrolide
s (e.g.
Azithromycin
)
Reduces clearance of other drugs
Warfarin
(
Coumadin
)
Decrease
Warfarin
dose 20% at start of Amiodarone
Expect INR stabilization to take as long as 6-8 weeks
Direct Oral Anticoagulant
s (e.g.
Rivaroxaban
) likely also interact, but effect is not measurable
Theophylline
Quinidine
Procainamide
Flecainide
Digoxin
(Levels may be increased by 70%)
Decrease
Digoxin
dose by 50% on starting Amiodarone
Statin
s
Simvastatin
(risk of
Myopathy
if dose >20 mg/day)
Atorvastatin
likely also interacts
Pravastatin
and
Rosuvastatin
are less likely to interact
Sildenafil
(
Viagra
)
Cyclosporine
Severe
Bradycardia
when combined with Sofosbuvir (Sovaldi)
See
Hepatitis C Antiviral Regimen
Has resulted in
Cardiac Arrest
and pacer placement
Avoid combining Amiodarone with Sofosbuvir (Sovaldi)
If unable to avoid combination
Admit for cardiac monitoring for 48 hours when initiating combination
Patient should monitor
Heart Rate
at home for 2 weeks after initiating dose
Patients should return for light headed, dizzy,
Near Syncope
,
Heart Rate
<60 bpm
References
FDA Alert
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm439662.htm
Dosing
Adult
Life-threatening
Arrhythmia
(
Wide Complex Tachycardia
)
Intravenous Dosing
Load: 150 mg over 10 minutes
May be repeated in 10 to 30 minutes
Maintenance
First: 1 mg/min for 6 hours
Next: 0.5 mg/min for 18 hours
Last: Reduce IV dose and convert to oral dosing
Oral Dosing
Load: 800 to 1600 mg PO per day in divided dosing
Continue daily until total of 10 grams given
Maintenance: 200-400 mg orally daily
Maximum: 2 grams per day total
Pulse
less
Arrhythmia
(e.g.
Ventricular Fibrillation
)
Load: 300 mg in 20-30 ml Saline rapid IV infusion
Maintenance and maximum dose as above
Atrial Fibrillation
Load: 400 to 800 mg orally per day in divided dosing
Continue daily until total of 10 grams given
Maintenance: 100-200 mg orally daily
Dosing
Child (Life-threatening
Arrhythmia
)
Dose: 5 mg/kg IV or IO
Administer over 20 to 60 minutes (unless pulseless)
Monitoring
Baseline labs
Chest XRay
Thyroid Stimulating Hormone
(TSH)
Aspartate Aminotransferase
(AST)
Alanine Aminotransferase
(ALT)
Pulmonary Function Test
s (including
DLCO
)
Consider ophthalmologic baseline exam
Other Monitoring
Closely monitor heart rhythm in first week of therapy
Prothrombin Time
with INR if on
Warfarin
Serum
Digoxin
level (as needed)
Repeat Lab testing at 3 months and then every 6 months
Thyroid Stimulating Hormone
(TSH)
Aspartate Aminotransferase
(AST)
Alanine Aminotransferase
(ALT)
Additional testing
Chest XRay
and
Pulmonary Function Test
s (with
DLCO
)
Indicated for suspected pneumonitis
Other anticipatory guidance
Use
Sunscreen
May prevent
Skin Discoloration
(as well as photosensitivity)
References
Katzung (1989) Pharmacology, Lange, p. 176
(2019) Presc Lett 26(1): 5
(2000) Circulation 102(suppl I): 86-89 [PubMed]
Siddoway (2003) Am Fam Physician 68:2189-96 [PubMed]
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