Why this drug is interesting
Amiodarone is classified as a Vaughan Williams class III agent, which is true but misleading. It blocks potassium channels, sodium channels and calcium channels, and antagonises alpha and beta adrenoceptors. It behaves as though it belongs to all four classes at once, which is why it is effective across an unusually wide range of arrhythmias — and why its adverse effects are similarly indiscriminate.
It is also structurally iodine-rich: roughly 112 mg of iodine per pre-filled syringe, against a daily dietary requirement of about 150 micrograms.1 That single fact explains the thyroid disease, and hints at the broader theme — amiodarone deposits in tissue, persists for months, and causes trouble in organs that have nothing to do with cardiac rhythm.
Pharmacology
Mechanism
The dominant electrophysiological action is potassium channel blockade, prolonging repolarisation, action potential duration and the effective refractory period across atrial, nodal, His-Purkinje and ventricular tissue — which lengthens the QT interval and is the basis of its class III designation.
Alongside this it produces sodium channel blockade (slowing conduction), calcium channel blockade (slowing sinus rate and AV conduction), and non-competitive alpha and beta blockade (contributing to hypotension and bradycardia, especially with rapid intravenous administration).
Kinetics — the numbers that make this drug unusual
- Half-life
- 20 to 100 days, varying widely between individuals1
- Onset after IV
- Maximal effect within about 15 minutes, declining over 4 hours as it distributes into tissue
- Distribution
- Extensive tissue deposition — fat, lung, liver, thyroid, cornea, skin; tissue saturation takes one to several months
- Metabolism
- Hepatic, to the active metabolite desethylamiodarone
- Elimination
- Hepatic and biliary; only about 10% renally — so no dose adjustment in renal impairment
- After stopping
- Excretion continues over several months
Indications and dosing
The licence is deliberately restrictive: amiodarone is indicated only for severe cardiac rhythm disorders not responding to other therapies, or where other treatments cannot be used.1 That covers AV nodal arrhythmias, supraventricular tachycardias, atrial flutter and fibrillation, and life-threatening ventricular arrhythmias — with the intravenous route reserved for when a rapid response is needed or oral administration is impossible.
Cardiac arrest — shock-refractory VF and pulseless VT
| Source | Dose |
|---|---|
| SmPC1 | 300 mg (or 5 mg/kg) as a rapid injection; a further 150 mg (or 2.5 mg/kg) may be considered if VF persists |
| RCUK ALS algorithm3 | 300 mg after the 3rd shock; a further 150 mg after the 5th shock |
The peri-arrest and stable patient
- Standard regimen: 5 mg/kg by intravenous infusion over 20 minutes to 2 hours, diluted in 250 mL of 5% dextrose
- May be followed by repeat infusion up to 1200 mg (approximately 15 mg/kg) in 24 hours
- In extreme emergency only, at the clinician's discretion: 150–300 mg in 10–20 mL of 5% dextrose as a slow injection over a minimum of 3 minutes
- Unstable tachyarrhythmia (RCUK 2025) — after up to 3 synchronised shocks fail: amiodarone 300 mg IV over 10–20 min, OR procainamide 10–15 mg/kg (max 1 g) over 20 min, then repeat synchronised shock3
- Stable broad-complex regular tachycardia (RCUK 2025) — where sedation/anaesthesia risk is too high for cardioversion, procainamide 10–15 mg/kg over 20 min is listed first; amiodarone 300 mg IV over 10–60 min then 900 mg over 24 h is the option if procainamide is unavailable or contraindicated3
Administration environment
The SmPC requires that intravenous amiodarone be used only in a special care unit under continuous ECG and blood pressure monitoring.1 In practice this means resus or critical care, not a cubicle.
Contraindications and cautions
Contraindications (outside cardiac arrest)
- Hypersensitivity to amiodarone, to iodine, or to any excipient
- Sinus bradycardia, sino-atrial heart block and sick sinus syndrome in patients without a pacemaker
- Evidence or history of thyroid dysfunction
- Severe respiratory failure, circulatory collapse or severe arterial hypotension
- Concomitant QT-prolonging drugs
- Neonates — the intravenous formulation contains benzyl alcohol (about 200 mg per 10 mL pre-filled syringe)
- Pregnancy and lactation — permitted only in life-threatening circumstances
Key warnings
- Sofosbuvir-containing regimens — life-threatening bradycardia and heart block have been observed; cardiac monitoring is mandatory for the first 48 hours and daily heart-rate monitoring for 2 weeks
- Thyroid function should be tested before therapy, and monitored during it
- Pulmonary toxicity — new dyspnoea or non-productive cough may indicate interstitial pneumonitis
- Hepatic injury — severe hepatocellular insufficiency can occur within the first 24 hours of intravenous amiodarone and may be fatal
- Prior to heart transplantation, amiodarone use has been associated with increased risk of primary graft dysfunction
Toxicity — the long-term picture
Emergency clinicians give amiodarone acutely, but frequently encounter its chronic toxicity in patients presenting with something apparently unrelated. Recognising the pattern is a genuinely useful diagnostic skill.
| System | Manifestation |
|---|---|
| Thyroid | Both hypo- and hyperthyroidism; amiodarone potently inhibits the T4-to-T3 converting enzyme, and the iodine load drives autonomous production |
| Pulmonary | Interstitial pneumonitis, organising pneumonia, and pulmonary fibrosis — presenting as progressive dyspnoea and dry cough; potentially fatal |
| Hepatic | Transaminase rise, hepatitis, cirrhosis; acute severe hepatocellular injury within 24 hours of IV use |
| Ocular | Corneal microdeposits in nearly all long-term users — usually asymptomatic; optic neuropathy is rare but serious |
| Dermatological | Photosensitivity, and the characteristic slate-grey skin discolouration |
| Neurological | Peripheral neuropathy, tremor, ataxia |
| Cardiac | Bradycardia, heart block, QT prolongation — though torsades is less frequent than the QT effect alone would predict |
Interactions
Amiodarone inhibits several cytochrome P450 enzymes and P-glycoprotein, and its very long half-life means interactions persist for months after discontinuation.
| Drug | Effect | Action |
|---|---|---|
| Digoxin | Plasma digoxin concentration rises | Halve the digoxin dose |
| Warfarin | Anticoagulant effect potentiated | Reduce warfarin dose; monitor INR more frequently during and after amiodarone |
| Flecainide | Concentration increased | Reduce flecainide dose by 50% and monitor closely |
| QT-prolonging drugs — class Ia and III antiarrhythmics, some antipsychotics, lithium, tricyclics, some antihistamines and antimalarials | Additive QT prolongation, torsades risk | Contraindicated |
| Sofosbuvir regimens | Severe bradycardia and heart block | Not recommended; if unavoidable, intensive monitoring |
| Beta-blockers, diltiazem, verapamil | Additive bradycardia and AV block | Not recommended |
| Statins metabolised by CYP3A4 — simvastatin, atorvastatin | Increased myotoxicity risk | Dose limitation or alternative statin |
Critical appraisal
What the cardiac arrest trials actually showed
This is the part most worth getting right, because amiodarone's place in the ALS algorithm is often assumed to rest on a survival benefit that the trials did not demonstrate.
- ARREST (referenced within the SmPC itself) randomised 504 patients with out-of-hospital VF or pulseless VT refractory to three or more shocks. Amiodarone significantly improved survival to hospital admission — 44% versus 34% — but the trial was not powered for, and did not demonstrate, improved survival to discharge.1
- ALIVE compared amiodarone with lidocaine and again found better survival to hospital admission, without a demonstrated discharge benefit.
- ALPS, a large randomised trial of amiodarone versus lidocaine versus placebo in out-of-hospital shock-refractory VF/pVT, found no statistically significant difference in survival to hospital discharge overall, though there were signals of benefit in bystander-witnessed arrests.4
Wider appraisal points
- The risk–benefit calculation is entirely different acutely versus chronically. A single 300 mg dose during resuscitation carries essentially no toxicity risk. Long-term therapy carries substantial multi-organ risk, and the decision to initiate it is not an emergency department decision.
- The licence is narrower than the prescribing. "Only for severe rhythm disorders not responding to other therapies" is a high bar, and amiodarone is often reached for earlier than that language implies.
- Its breadth is both the strength and the problem. A drug that works on most arrhythmias in most patients is attractive in an emergency; the same promiscuity is what produces thyroid, lung, liver, eye and skin toxicity.
- It is no longer the automatic first choice in stable VT. Procainamide outperformed amiodarone for tolerated wide-QRS tachycardia in PROCAMIO, and the RCUK 2025 algorithm now lists procainamide first, with amiodarone as the alternative when procainamide is unavailable or contraindicated.3 Practice in many UK departments has not caught up — largely because procainamide supply is unreliable, not because amiodarone is preferred. See Procainamide.
References
- 1Amiodarone 30 mg/ml Solution for injection/infusion in pre-filled syringe — Summary of Product Characteristics. electronic Medicines Compendium. Sections 4.1–4.5, 5.1–5.2. Verified 20 Aug 2026.
- 2Amiodarone hydrochloride — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk
- 3Resuscitation Council UK. Adult advanced life support algorithm and Adult tachyarrhythmia algorithm, 2025. resus.org.uk — mirrored at lifesupport.resusdoc.uk. The 2025 tachyarrhythmia algorithm lists procainamide ahead of amiodarone for stable broad-complex regular tachycardia, and directs avoidance of amiodarone in polymorphic VT with QT prolongation.
- 4Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest (ALPS). N Engl J Med 2016;374(18):1711–22.
- 5Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation (ARREST). N Engl J Med 1999;341(12):871–78.
- 6Ortiz M, Martín A, Arribas F, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia (PROCAMIO). Eur Heart J 2017;38(17):1329–35.