Amiodarone
Regulatory sources consulted
- AEMPS CIMA FT 81291: https://cima.aemps.es/cima/dochtml/ft/81291/FT_81291.html
- PubMed PMID:36066275 ↗
- CredibleMeds.org
- Flockhart Table (Indiana University)
- Professional clinical pharmacology knowledge
- AEMPS CIMA · nº registro 81291 ↗
- RxNorm rxcui 703 ↗
Approved indications
- Treatment of severe arrhythmias (ventricular tachycardia, ventricular fibrillation) and prevention of their recurrence, when other antiarrhythmics are not effective or tolerated.
- Treatment and prevention of recurrence of atrial fibrillation and atrial flutter.
- Tachyarrhythmias associated with Wolff-Parkinson-White syndrome.
Contraindications
Absolute
- Sinus bradycardia, sinoatrial block, and sick sinus syndrome (risk of sinus arrest).
- 2nd or 3rd degree atrioventricular block without a pacemaker.
- Current or past thyroid disease. The high iodine content interferes with thyroid function.
- Pregnancy and breastfeeding.
Clinical warnings
- Boxed warning · Pulmonary Toxicity: Can cause hypersensitivity pneumonitis or pulmonary fibrosis, which can be fatal. Monitor for respiratory symptoms and perform baseline and periodic chest X-rays. — AEMPS SPC
- Boxed warning · Hepatotoxicity: Can cause severe liver injury, sometimes fatal. Monitor liver enzymes (AST, ALT) before starting and every 6 months during treatment. — AEMPS SPC
- Major warning · Worsening of arrhythmias (proarrhythmia): Can induce new arrhythmias or worsen existing ones, including Torsades de Pointes. — AEMPS SPC
Drug interactions
- HighWarfarinB01AA03
Mechanism: Inhibition of warfarin metabolism (CYP2C9 substrate) by amiodarone, significantly increasing INR and bleeding risk.
Recommendation: Reduce warfarin dose by 30-50% when starting amiodarone. Monitor INR frequently (e.g., 2-3 times per week) until stable.
AEMPS SPC
- HighDigoxinC01AA05
Mechanism: Inhibition of the P-glycoprotein (P-gp) transporter by amiodarone, reducing digoxin's renal clearance and increasing its serum levels and risk of toxicity.
Recommendation: Reduce digoxin dose by 50% when starting amiodarone. Monitor serum digoxin levels and signs of toxicity.
AEMPS SPC
- HighSimvastatinC10AA01
Mechanism: Inhibition of simvastatin metabolism (CYP3A4 substrate) by amiodarone, increasing the risk of myopathy and rhabdomyolysis.
Recommendation: Do not exceed a dose of 20 mg/day of simvastatin in patients taking amiodarone. Consider using a statin not metabolized by CYP3A4 (e.g., pravastatin, rosuvastatin).
AEMPS SPC
Adverse events
Common (≥1%)
corneal microdeposits · photosensitivity · nausea · taste disturbance · elevated transaminases · hypothyroidism · hyperthyroidism · bradycardia
Rare but serious
pulmonary fibrosis · fulminant hepatic failure · Torsades de Pointes · optic neuritis · Stevens-Johnson syndrome · thyroid storm
Pregnancy and lactation
FDA category: D
Contraindicated in pregnancy and breastfeeding. The high iodine content can cause hypothyroidism and goiter in the fetus and infant. It crosses the placenta and is excreted in breast milk.
Recent literature (PubMed)
Revisión que posiciona a la amiodarona como el antiarrítmico más potente, pero subraya su toxicidad extracardíaca como un factor limitante. Las guías de la ESC recomiendan considerar otros fármacos primero para el control del ritmo en fibrilación auricular (FA) siempre que sea posible. El artículo critica el uso liberal de amiodarona, especialmente en pacientes sin cardiopatía estructural, donde se asocia con un aumento de la mortalidad no cardiovascular, y aboga por una mejor apreciación de sus riesgos en comparación con alternativas como la ablación con catéter.