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Drug Reference

amiodarone

Class III antiarrhythmic· Brands: Cordarone, Nexterone, PaceroneIVPO

Mechanism of action
Class III antiarrhythmic (K⁺ channel blockade plus Na⁺/Ca²⁺/β effects).
Pharmacokinetics
Oral bioavailability is variable, ranging from 30% to 80%. Amiodarone is extensively distributed into adipose tissue and highly protein-bound. It has a very long elimination half-life of about 40 to 55 days. It is metabolised in the liver by CYP3A4 and CYP2C8 to an active metabolite, desethylamiodarone. Excretion is mainly via the bile and faeces. Therapeutic effects may take days to weeks to appear.
Indications & dosing

Rhythm control in atrial fibrillation

    Contraindications & precautions
    • Hypersensitivity to amiodarone or any excipient · Rare but cross-reactivity possible with iodine-containing compounds.
    • Sinus bradycardia or sinoatrial block · Amiodarone can worsen bradycardia; pacemaker may be required.
    • Second or third degree atrioventricular block without a functioning pacemaker · Risk of complete heart block.
    • Thyroid dysfunction (hyperthyroidism or hypothyroidism) · Amiodarone contains iodine and can affect thyroid function; use with caution and monitor.
    • Severe hepatic impairment · Amiodarone is metabolised in the liver; dose reduction or avoidance may be needed.
    • Monitor thyroid function (TSH, T4) before and during treatment; amiodarone can cause both hypo- and hyperthyroidism.
    • Monitor liver enzymes (ALT, AST) before and during treatment; risk of hepatotoxicity.
    • Monitor pulmonary function and advise patients to report dyspnoea or cough; risk of pulmonary toxicity.
    • Use with caution in patients with pre-existing QT prolongation or in combination with other QT-prolonging drugs; risk of torsades de pointes.
    • Monitor heart rate and ECG regularly; dose adjustment may be needed for bradycardia or conduction disturbances.
    • Avoid use during pregnancy and breastfeeding unless potential benefit outweighs risk; amiodarone crosses placenta and is excreted in breast milk.
    Adverse effects
    • Thyroid dysfunctionserious
    • Pulmonary fibrosisserious
    • Photosensitivity
    Interactions
    • bisoprololmajorMonitor heart rate and blood pressure closely, especially after starting amiodarone. Consider reducing the bisoprolol dose or avoiding the combination in patients with bradycardia, heart block, or heart failure. Adjust doses based on clinical response and ECG findings.
    • metoprololmajorAlternative beta-blockers with minimal CYP2D6 metabolism (e.g., atenolol or nadolol) may be considered, but always assess clinically.
    • carvedilolmajorMonitor heart rate, blood pressure, and ECG at baseline and regularly during co-therapy. Use low initial doses of carvedilol and titrate cautiously. Consider alternative agents if severe bradycardia or heart block occurs. If co-prescription is necessary, ensure close follow-up.
    • apixabanmoderateConcomitant use of amiodarone and apixaban may require caution. Check the current apixaban prescribing information, as some formularies advise a reduced apixaban dose (e.g., 2.5 mg twice daily) when given with strong inhibitors of both CYP3A4 and P-gp. If no dose reduction is made, closely monitor the patient for clinical evidence of bleeding. Reassess the need for amiodarone and consider alternative anti-arrhythmic options when possible.
    • warfarinmajorAvoid the combination if possible. If concurrent use is necessary, reduce the warfarin dose, typically by 30-50%, and monitor INR frequently (at least weekly) during the first few weeks of therapy and after any dose change. Continue to monitor INR for several weeks after amiodarone is stopped, as its effects are prolonged. Consider alternative antiarrhythmic agents where appropriate.
    • diltiazemmajorAvoid co-prescription where possible. If the combination is necessary, monitor ECG, heart rate, and blood pressure, and consider dose reduction. Advise patients to report palpitations, dizziness, or syncope.
    • atorvastatinmajorAvoid co-prescribing high-dose atorvastatin with amiodarone. If combination is necessary, use the lowest effective dose of atorvastatin (e.g., starting at 10 mg/day) and monitor for signs of myopathy. Counsel the patient to report unexplained muscle pain or weakness. Measure creatine kinase at baseline and if symptoms develop. Consider alternative lipid-lowering therapy (e.g., pravastatin or rosuvastatin, which are less dependent on CYP3A4) where possible.
    • levothyroxinemoderateMonitor thyroid function tests (TSH, free T4, free T3) at baseline before starting amiodarone, then every 1-3 months during the first year of therapy, and periodically thereafter. Adjust levothyroxine dose based on TSH and free T4 levels. Consider alternative antiarrhythmic agents if thyroid dysfunction is difficult to manage.
    • ciprofloxacinmajorConsider alternative antibiotics with less QT prolonging activity, such as doxycycline, if clinically appropriate.
    • azithromycinmajorAvoid concurrent use if possible. If co-administration is necessary, use the lowest effective doses and closely monitor the QT interval with electrocardiography before and during therapy. Assess and correct electrolyte imbalances. Consider alternative antibiotics that do not prolong the QT interval. Seek specialist advice if the patient has additional risk factors.
    • methadonemajorAvoid co-prescription where possible. If the combination is necessary, obtain a baseline ECG and electrolyte measurements (potassium, magnesium), and repeat ECG regularly during therapy, especially after dose changes. Correct any electrolyte abnormalities. Consider alternative therapies that do not prolong the QT interval. Monitor for signs of arrhythmia and advise the patient to report palpitations or syncope.
    • digoxinmajorIf co-prescription is necessary, consider reducing the digoxin maintenance dose by approximately 50% (or use a lower starting dose) and monitor serum digoxin concentrations, renal function, and ECG. Monitor for signs of digoxin toxicity. Adjust digoxin dose based on levels and clinical response. Alternative antiarrhythmics may be considered to avoid the interaction.
    • clarithromycincontraindicatedCoadministration is contraindicated. Avoid the combination and consider alternative antibacterial therapy. If coadministration is absolutely necessary, it should be done in a hospital setting with continuous ECG monitoring and immediate availability of resuscitation facilities, but ideally the combination should not be used.
    • dabigatranmajorIf coadministration is necessary, reduce the dabigatran dose to 150 mg daily for patients with creatinine clearance 30-50 mL/min. For other patients, consider dose reduction or increased monitoring for bleeding. Avoid in severe renal impairment. Alternative anticoagulants should be considered.
    • simvastatinmajorAvoid concomitant use if possible. If combination is necessary, limit simvastatin dose to no more than 20 mg daily and monitor patients for signs of myopathy, including creatine kinase levels. Consider alternative statins less dependent on CYP3A4, such as pravastatin or rosuvastatin.
    Renal & hepatic adjustment
    • Hepatic impairment (mild): No dose adjustment required; monitor hepatic function.
    • Hepatic impairment (moderate): No dose adjustment required; use caution and monitor hepatic function.
    • Hepatic impairment (severe): Avoid use; consider alternative antiarrhythmic. (avoid)
    Monitoring, pregnancy & toxicity
    • ECG (heart rate and QT interval) · Baseline, then at regular intervals during therapy
    • Thyroid function tests (TSH, free T4, T3) · Baseline, then every 6-12 months
    • Pulmonary function and chest X-ray · Baseline, then if symptoms of dyspnoea or cough
    • Liver function tests (AST, ALT, bilirubin) · Baseline, then every 6 months
    • Ophthalmologic examination · Baseline, then if visual symptoms
    • Skin examination for discolouration · Routine clinical review
    • Pregnancy: Not recommended in pregnancy. Amiodarone can cause fetal thyroid dysfunction and goitre; use only for life-threatening arrhythmias when other treatments are ineffective, and discuss risks with the patient.
    • Toxicity: Pulmonary toxicity (pneumonitis, fibrosis) · Discontinue amiodarone; consider corticosteroids and supportive care.
    • Toxicity: Thyroid dysfunction (hypo- or hyperthyroidism) · Monitor thyroid function; treat with hormone replacement or antithyroid drugs as appropriate; consider discontinuation.
    • Toxicity: Cardiac toxicity (bradycardia, QT prolongation) · Monitor ECG; supportive care; may require temporary pacing.
    • Toxicity: Skin discolouration and photosensitivity · Advise sun protection; discolouration may resolve slowly after discontinuation.
    Clinical notes
    Amiodarone is used for life-threatening ventricular arrhythmias and for atrial fibrillation, especially when other agents fail. It requires specialist initiation and close monitoring for adverse effects including thyroid dysfunction, pulmonary toxicity, hepatotoxicity, and corneal microdeposits. It interacts with warfarin, digoxin, and beta-blockers, increasing their concentrations. A loading dose is commonly given, with an oral maintenance dose adjusted over time. Every dose must be verified and prescribing information consulted before use.

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    BNF; local formulary