Amiodarone

ADMINISTRATION ROUTES:

PO, NG, IV

ALTERNATIVE NAMES:

Cordarone-X

ICU INDICATIONS:

1. VT, VF

2. Atrial tachycardias

PRESENTATION AND ADMINISTRATION:

PO / NG:

200 mg tablet

Tablets may be crushed for NG administration

IV:

150 mg in 3 mL vials. Amiodarone IV is a sterile clear, pale-yellow solution visually free from particulate matter

Compatible with 5% dextrose only

Do not use PVC infusion bags for infusion as adsorption may occur. When mixing for infusion use only EXCEL container 250 mL bags of 5% dextrose injection USP. Add 450 mg amiodarone.

For stat dose (usually 300 mg) add to a standard 100 mL plastic bag of 5% dextrose. Administration via a central line is preferred

Store at room temperature. Do not refrigerate

DOSAGE:

Tachydysrhythmias:

IV load 300-450 mg in 100 mL 5% dextrose over 20 minutes to two hours

Ongoing infusion:

450 mg in 250 mL glucose 5% over 12 hours x 2

i.e. 900 mg over 24 hours. Dilute in 5% dextrose only (using Excel Container 250 mL 5% Dextrose Injection USP)

Note: 300 mg stat may be considered for VT/VF (this should be added to 10-20 mL of 5% dextrose and administered by slow IV push over 3 minutes or more)

Transition from IV to oral therapy:

200 mg PO 8 hourly for 1 week followed by 200 mg PO 12 hourly for one week followed by 200 mg PO 12-24 hourly thereafter

Note: higher oral dosages (up to 1600 mg per day can be used in patients who have not received a full IV load). An overlap of intravenous and oral medication of up to two days is recommended.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

The safety and efficacy of amiodarone in the paediatric population have not been established; its use in paediatric patients is not recommended.

CLINICAL PHARMACOLOGY:

Amiodarone is generally considered a Class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes.

CONTRAINDICATIONS:

1. Known hypersensitivity to any of the components of amiodarone, including iodine

2. Second- or third-degree AV block unless a functioning pacemaker is available

WARNINGS:

Hypotension

Hypotension is the most common adverse effect seen with amiodarone. Hypotension should be treated by vasopressor drugs, positive inotropic agents, and volume expansion. Slowing the rate of infusion may also be effective.

Bradycardia and AV Block

Drug-related bradycardia should be treated by discontinuing amiodarone. Additional measures including drug therapy and/or temporary pacing may be required if bradycardia does not resolve.

PRECAUTIONS:

General:

Liver enzyme elevations in patients on amiodarone are not uncommon; however, baseline abnormalities in hepatic enzymes are not a contraindication to treatment. Rare cases of fatal hepatocellular necrosis after treatment with amiodarone have been reported.

Like all antiarrhythmic agents, amiodarone may cause a worsening of existing arrhythmias or precipitate a new arrhythmia.

There have been reports of acute-onset (days to weeks) pulmonary injury in patients treated with amiodarone. Findings have included pulmonary infiltrates on X-ray, bronchospasm, wheezing, fever, dyspnoea, cough, haemoptysis, and hypoxia. Some cases have progressed to respiratory failure and/or death.

Laboratory Tests:

Consider measurement of thyroid function as a baseline (if not previously measured)

Drug/Laboratory Test Interactions:

Amiodarone alters the results of thyroid-function tests, causing an increase in serum T4 and serum reverse T3, and a decline in serum T3 levels. Despite these biochemical changes, most patients remain clinically euthyroid.

IMPORTANT DRUG INTERACTIONS IN ICU:

Amiodarone with:

Cyclosporin: increased cyclosporin levels; dosage reduction of cyclosporin required

Digoxin: increased digoxin levels; dosage reduction of digoxin required. Antiarrhythmics: in general, any added antiarrhythmic drug should be initiated at a lower than usual dose with careful monitoring

Antihypertensives: beta blockers and calcium channel blockers may lead to increased risk of bradycardia when combined with amiodarone

Warfarin: dose of warfarin should be reduced by 1/2 to 1/3rd and INR should be closely monitored

Rifampin: decreases in serum concentrations of amiodarone

Fluoroquinolones: increased risk of QTc prolongation when combined with amiodarone

Macrolides: increased risk of QTc prolongation when combined with amiodarone

ADVERSE REACTIONS:

Body as a Whole:

Fever

Cardiovascular System:

Bradycardia, congestive heart failure, hypotension, ventricular tachycardia

Respiratory System:

dyspnoea, cough, haemoptysis, wheezing, hypoxia, pulmonary infiltrates

Digestive System:

Nausea, deranged LFTs

Nervous System:

Hallucinations, confusional state, pseudotumour cerebri

Endocrine System:

Hypothyroidism, hyperthyroidism, SIADH

Skin:

Toxic epidermal necrolysis