Class III antiarrhythmics (Vaughan Williams)
ATC code: C01BD01 (Amiodarone)
Brand names
Cordarone, Pacerone, Nexterone
Iodine-containing benzofuran antiarrhythmic with multichannel action: blocks potassium channels (class III), sodium (class I), and calcium (class IV), and non-competitively inhibits beta-adrenoceptors (class II). Prolongs action potential and refractory period, slows AV conduction. Large volume of distribution – accumulates in fat, liver, lung, and thyroid. Half-life 25–110 days – withdrawal effects emerge slowly. Contains 37.3 % iodine by mass – one 200 mg tablet has ~75 mg iodine (daily requirement ~150 µg).
First line
Per AF 2024, amiodarone is first-line antiarrhythmic for sinus rhythm maintenance in patients with structural heart disease (HFrEF, CAD, hypertrophy). With preserved cardiac structure, propafenone and are preferred – they have less extracardiac toxicity. Oral loading 600–800 mg/day for 1–4 weeks, maintenance 100–200 mg/day. IV loading for emergency cardioversion: 5 mg/kg over 30 minutes.
Drug of choice in HFrEF, CAD, hypertrophic cardiomyopathy, and other structural heart disease.
First line
Per ACLS 2020 and ERC 2021, in refractory VF or polymorphic VT after the third ineffective shock, give amiodarone 300 mg IV bolus. If arrhythmia persists, repeat 150 mg. Lidocaine 1–1.5 mg/kg is the alternative when amiodarone is unavailable. The large ALPS 2016 RCT showed no significant effect of either agent on survival to hospital discharge, but amiodarone reduced rhythm recurrence during resuscitation.
First line
Per Ventricular Arrhythmias 2022, amiodarone is the drug of choice in haemodynamically stable sustained monomorphic VT. IV 150 mg over 10 minutes, then 1 mg/min for 6 hours, then 0.5 mg/min for 18 hours (~1 g total day one). Electrical cardioversion is used immediately for haemodynamic instability. Long-term secondary prevention: ICD in high-risk patients; amiodarone is added to reduce ICD shock burden.
Third line
Per AF 2024, amiodarone is not used as first- or second-line for long-term rate control – extracardiac toxicity (pulmonary fibrosis, thyroid dysfunction, hepatotoxicity, corneal deposits) makes the risk/benefit unfavourable without arrhythmic threat. IV amiodarone is used acutely in fast-AF with haemodynamic instability in HF patients where beta-blockers and non-dihydropyridine calcium antagonists are contraindicated.
Reserve option for rate control – only when beta-blockers, non-dihydropyridine calcium antagonists, and digoxin fail or are not tolerated.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Amiodarone is a class III antiarrhythmic drug. It is prescribed for dangerous ventricular arrhythmias and for rhythm control in atrial fibrillation when other drugs are ineffective or contraindicated ( 2024). In anti-aging practices, amiodarone is prescribed to healthy adults as a universal antiarrhythmic. In people without arrhythmias, no clinical studies of prophylactic use exist, and such prescription is extremely dangerous. Amiodarone has a severe adverse-effect profile: pulmonary fibrosis (irreversible), thyrotoxicosis and hypothyroidism (amiodarone contains 37% iodine by mass), hepatotoxicity up to acute liver failure, corneal deposits with visual impairment, photosensitization (bluish skin discoloration in sunlight), and QT prolongation. If amiodarone was prescribed to a person without a dangerous arrhythmia, seek a second opinion immediately: this prescription is extremely dangerous.
Grapefruit juice raises bioavailability of amiodarone and its active N-desethyl metabolite. QT prolongation and Torsades de Pointes risk increase. Avoid throughout the course.
Source: FDA: Cordarone (amiodarone) prescribing information (2021)
56 pairs found. Sorted from critical to minor.
Mechanism
Amiodarone prolongs the QT interval. Co-trimoxazole (trimethoprim + sulfamethoxazole) also prolongs QT and amplifies the effect in combination. UK MHRA Cordarone X SmPC Section 4.3 specifically lists QT-prolonging drugs as contraindications. Co-trimoxazole additionally inhibits CYP2C9, a partial amiodarone clearance route.
Symptoms
QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases progress to torsades de pointes with risk of ventricular fibrillation. Risk rises with hypokalaemia (which co-trimoxazole can worsen).
Management
The combination is not prescribed. For UTI in patients on amiodarone, use a cephalosporin, nitrofurantoin, or fosfomycin. For Pneumocystis infection (where co-trimoxazole is irreplaceable), continuous ECG monitoring and daily potassium and magnesium checks.
Mechanism
Amiodarone blocks P-glycoprotein in the intestine and renal tubules – the main dabigatran-style clearance route of digoxin. Digoxin plasma levels rise 1.7- to 2.5-fold. The narrow therapeutic window of digoxin turns any rise into a risk of acute toxicity.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. In older adults: confusion, dizziness. Symptoms appear 1–2 weeks after starting amiodarone.
Management
When amiodarone is started, halve the digoxin dose immediately. Measure digoxin level after 1 week (target 0.5–0.9 ng/mL in heart failure). Check potassium and magnesium monthly: hypokalaemia worsens digoxin toxicity.
Mechanism
Amiodarone and dronedarone are class III antiarrhythmics with overlapping mechanism and additive QT prolongation. Dronedarone was developed as a less toxic replacement for amiodarone, so combining them is not meaningful.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk rises with hypokalaemia and hypomagnesaemia.
Management
The combination is not prescribed. Choose one: amiodarone for high-risk atrial fibrillation with reduced ejection fraction, dronedarone for preserved ejection fraction without heart failure.
Mechanism
Dual mechanism: ritonavir strongly inhibits CYP3A4, the partial clearance route of amiodarone, raising amiodarone levels. Both drugs also prolong QT. The lists the combination as an absolute contraindication.
Symptoms
QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases progress to torsades de pointes with risk of ventricular fibrillation and sudden cardiac death.
Management
The combination is not prescribed. For HIV-positive patients with atrial fibrillation, use a beta-blocker for rate control or catheter ablation for rhythm control. Where possible, switch antiretroviral therapy to a ritonavir-free regimen.
Mechanism
Warfarin acts via two stereoisomers: S-warfarin (5-fold more active) and R-warfarin. Amiodarone strongly inhibits CYP2C9 (the S-warfarin pathway) and, to a lesser extent, CYP3A4 (the R-warfarin pathway). The active form accumulates; the international normalised ratio (INR, a marker of blood clotting) rises 2- to 4-fold. The effect develops slowly over 1–7 weeks because amiodarone has a very long half-life.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal and intracranial haemorrhage with fatal outcomes – reported at INR above 10.
Management
The combination is acceptable when amiodarone cannot be replaced by another antiarrhythmic. Reduce warfarin dose empirically by 30–50% at the time amiodarone is added. Check INR every 3–5 days for the first month, then every 2 weeks. The interaction persists for several weeks after amiodarone is stopped – return warfarin to baseline dose gradually.
Mechanism
Dual mechanism: both prolong QT, and amitriptyline (TCA) additionally blocks cardiac sodium channels – His-Purkinje conduction is depressed. High risk of torsades de pointes and AV block.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antidepressants with minimal QT effect: sertraline (up to 100 mg/day) or agomelatine. For neuropathic pain, replace amitriptyline with gabapentin or pregabalin.
Mechanism
Amiodarone moderately blocks P-glycoprotein and CYP3A4 – two apixaban clearance routes. Apixaban plasma levels rise by about 50%, with a modest bleeding risk increase.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
The combination is acceptable without dose change in patients with atrial fibrillation. In elderly patients weighing ≤60 kg or with serum creatinine ≥133 µmol/L, reduce apixaban to 2.5 mg twice daily. PPI cover with pantoprazole is advisable.
Mechanism
Amiodarone moderately blocks CYP3A4 – a partial atorvastatin metabolic route. Atorvastatin plasma levels rise 1.5- to 2-fold; myopathy risk grows at doses of 40 mg and above.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Cap atorvastatin at 20 mg/day when amiodarone is added. If targets are missed, switch to pravastatin or rosuvastatin (less CYP3A4-dependent). Check creatine kinase at 4–6 weeks and on muscle symptoms.
Mechanism
Additive QT prolongation. Azithromycin received a 2013 warning for fatal ventricular arrhythmia risk, particularly in patients with risk factors. Amiodarone is a potent QT-prolonging drug.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: doxycycline or a cephalosporin. If azithromycin is needed, ECG before start and potassium and magnesium in range.
Mechanism
Additive bradycardia and AV conduction suppression. Bisoprolol is a selective beta-blocker; amiodarone non-competitively blocks β-receptors and suppresses the AV node.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall risk.
Management
The combination is appropriate in cardiology (atrial fibrillation, post-infarction). Reduce bisoprolol by 25–50% when starting amiodarone. Check pulse and ECG at 1 and 4 weeks.
Mechanism
Dual mechanism. Carbamazepine induces CYP3A4 and lowers amiodarone levels. Amiodarone blocks CYP3A4 and partially suppresses carbamazepine metabolism, so carbamazepine plasma levels may rise.
Symptoms
From amiodarone fall: atrial fibrillation symptoms return. From carbamazepine rise: ataxia, diplopia, nausea, hyponatraemia, drowsiness.
Management
Avoid the combination. Alternative anticonvulsants without induction: levetiracetam, lamotrigine. Alternative antiarrhythmic: beta-blocker for rate control or catheter ablation. If unavoidable, check carbamazepine plasma levels at 1–2 weeks.
Mechanism
Additive QT prolongation. Amiodarone strongly blocks IKr potassium channels, ciprofloxacin weakly but dose-dependently. Ciprofloxacin also inhibits CYP1A2 (a minor amiodarone clearance route).
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid where possible. Alternative antibiotic: a cephalosporin (no QT effect). If ciprofloxacin is needed, ECG before start and at day 3, with potassium and magnesium maintained.
Mechanism
Dual QT-prolongation risk. Citalopram carries an boxed warning about dose-dependent QT effect (FDA Celexa caps at 40 mg/day); amiodarone is a potent QT-prolonging drug.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antidepressants: mirtazapine or agomelatine (minimal QT effect). If citalopram is needed, cap at 20 mg/day; ECG before start and at 2 weeks.
Mechanism
Dual mechanism: both prolong QT, and clarithromycin blocks CYP3A4 – a partial amiodarone clearance route. Amiodarone and its active metabolite (N-desethyl-amiodarone) plasma levels rise.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: azithromycin or doxycycline (minimal CYP3A4 interaction). If clarithromycin is needed, ECG before start and every 3 days during therapy, with potassium and magnesium maintained.
Mechanism
Amiodarone blocks CYP3A4 and the P-glycoprotein transporter – two colchicine clearance routes. Colchicine plasma levels rise; myopathy and neuropathy risk grows.
Symptoms
Muscle weakness and pain, peripheral neuropathy (numbness, tingling in feet and hands), nausea, diarrhoea. Severe cases include pancytopenia and rhabdomyolysis. Symptoms appear within 1–4 weeks of co-administration.
Management
Do not prescribe in chronic kidney disease or impaired hepatic function. With preserved function, reduce colchicine to 0.3 mg every other day. Alternative for gout on amiodarone: intra-articular or short systemic glucocorticoid.
Mechanism
Amiodarone blocks intestinal P-glycoprotein – the main route of dabigatran absorption and elimination. Dabigatran plasma levels rise by 30–60%; bleeding risk increases.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black stools, blood in urine. Risk is higher in renal impairment.
Management
With creatinine clearance above 50 mL/min, standard dabigatran 150 mg twice daily is acceptable. At clearance 30–50 mL/min, reduce to 110 mg twice daily. Below 30 mL/min, do not prescribe the combination; switch to warfarin or apixaban.
Mechanism
Amiodarone blocks the P-glycoprotein transporter and renal tubular secretion of digoxin. Digoxin plasma levels rise 1.5- to 2-fold. The narrow therapeutic window converts any rise into acute toxicity risk.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. Older adults: confusion, dizziness. Symptoms appear within 1–2 weeks of co-administration.
Management
When amiodarone starts, halve the digoxin dose. Measure digoxin level at 1 week (target 0.5–0.9 ng/mL in heart failure). Check potassium and magnesium monthly: low values worsen digoxin toxicity.
Mechanism
Additive bradycardia and AV block. Third-degree AV block with syncope has been reported. Both drugs slow AV nodal conduction.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall risk.
Management
Avoid the combination. In atrial fibrillation, choose one strategy: amiodarone for rhythm control, diltiazem for rate control. Alternatives: a beta-blocker + digoxin or catheter ablation.
Mechanism
Escitalopram (SSRI) is a citalopram enantiomer with dose-dependent QT prolongation. The Lexapro label caps escitalopram at 20 mg/day specifically because of QT risk. Effects add with amiodarone.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid where possible. If escitalopram is needed, cap at 10 mg/day; ECG before start and at 2 weeks, with potassium and magnesium maintained. Alternative antidepressants with minimal QT effect: mirtazapine or agomelatine.
Mechanism
Dual mechanism: fluconazole prolongs QT (additive with amiodarone) and blocks CYP3A4 – a partial amiodarone clearance route. Amiodarone plasma levels rise.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antifungals: echinocandins (micafungin, caspofungin) for systemic mycoses or terbinafine for dermatophytosis. If fluconazole is needed, ECG before start and every 3 days during therapy.
Mechanism
Fluoxetine blocks CYP2D6 (a minor amiodarone clearance route) and modestly prolongs QT. Amiodarone plasma levels rise and QT effects add up. The long half-life of fluoxetine and norfluoxetine (up to 5 weeks) is relevant.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antidepressants with minimal QT effect and no CYP2D6 inhibition: mirtazapine or agomelatine. Interaction potential persists up to 5 weeks after fluoxetine discontinuation.
Mechanism
Furosemide (loop diuretic) increases potassium and magnesium loss. Low potassium and magnesium amplify amiodarone's QT-prolonging effect. Furosemide itself does not change amiodarone levels – the danger is the electrolyte shift.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is common (atrial fibrillation plus heart failure). Check potassium and magnesium every 1–3 months; if potassium drops below 4.0 mmol/L, add a potassium-sparing diuretic or potassium supplement; if magnesium falls below 0.7 mmol/L, supplement magnesium.
Sources
Mechanism
Additive QT prolongation, especially with parenteral (IV) haloperidol. Torsades de pointes and fatal arrhythmias have been reported, especially in ICU patients with hypokalaemia.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination, especially IV haloperidol. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole. For acute delirium in amiodarone patients: dexmedetomidine (no QT effect).
Mechanism
Hydrochlorothiazide (thiazide diuretic) increases potassium and magnesium loss. Low levels amplify amiodarone's QT-prolonging effect.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is common (hypertension plus atrial fibrillation). Check potassium and magnesium every 3 months; if potassium drops below 4.0 mmol/L, add a potassium-sparing diuretic or potassium supplement.
Sources
Mechanism
Indapamide (thiazide-like diuretic) increases potassium and magnesium loss. Low levels amplify amiodarone's QT-prolonging effect.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is common (hypertension plus atrial fibrillation). Check potassium and magnesium every 3 months; if potassium drops below 4.0 mmol/L, add a potassium-sparing diuretic or potassium supplement.
Mechanism
Ketoconazole strongly blocks CYP3A4 – the N-deethylation pathway of amiodarone. Amiodarone and its active metabolite (N-desethyl-amiodarone) levels rise; QT effect intensifies.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antifungals: terbinafine (no CYP3A4 effect) for dermatophytosis or echinocandins for systemic mycoses.
Mechanism
Dual mechanism. Amiodarone non-competitively blocks β-adrenoceptors and depresses atrioventricular (AV) conduction; metoprolol is a competitive β-blocker. Effects add up: lowered heart rate and AV conduction. Amiodarone also inhibits CYP2D6 and metoprolol plasma levels rise.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block, prolonged PR. In heart failure: worsening dyspnoea and oedema.
Management
The combination is appropriate in cardiology (atrial fibrillation, post-infarction care). Halve the metoprolol dose when starting amiodarone. Check pulse and ECG at 1 and 4 weeks. If pulse drops below 50 or second-degree AV block appears, adjust metoprolol further.
Sources
Mechanism
Metronidazole prolongs the QT interval. Combined with amiodarone, torsades de pointes has been reported, especially with hypokalaemia.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antibiotics without QT effect: a cephalosporin, amoxicillin-clavulanate, or fosfomycin. For anaerobic infection requiring metronidazole: ECG before start and at day 2.
Mechanism
Mirtazapine prolongs QT dose-dependently. Combined with amiodarone, torsades de pointes risk rises, especially in older patients and with hypokalaemia.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is acceptable at low mirtazapine doses (≤30 mg/day) and normal potassium. ECG before start and at 2 weeks. Alternative antidepressant with minimal QT effect: agomelatine.
Mechanism
Additive bradycardia and AV conduction suppression. Propranolol is non-selective, with higher risk than bisoprolol (affects β2 receptors, potentially causing bronchospasm in asthma).
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall risk.
Management
The combination is appropriate in cardiology. Reduce propranolol by 25–50% when starting amiodarone. Check pulse and ECG at 1 and 4 weeks. In asthma or COPD, a selective beta-blocker (bisoprolol) is preferred.
Mechanism
Amiodarone prolongs QT and weakly blocks CYP3A4 (the main quetiapine metabolic route). Quetiapine is a CYP3A4 substrate with QT effect at high doses. Additive QT prolongation plus moderate quetiapine level rise.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination at high quetiapine doses. At low doses (≤100 mg) and normal potassium and magnesium, the combination is acceptable with ECG monitoring at 2 weeks. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.
Mechanism
Rifampicin strongly induces CYP3A4 – the main N-deethylation pathway of amiodarone. Amiodarone and N-desethyl-amiodarone plasma levels fall by about 50%; antiarrhythmic effect weakens.
Symptoms
Atrial fibrillation symptoms return: palpitations, irregular pulse, fatigue, dyspnoea. Rhythm breakthroughs may require admission.
Management
During anti-TB therapy, replace amiodarone with a beta-blocker for rate control or plan catheter ablation. Induction persists for 2 weeks after rifampicin stops – restart amiodarone gradually.
Mechanism
Amiodarone moderately blocks CYP3A4 and P-glycoprotein – two rivaroxaban clearance routes. Rivaroxaban plasma levels rise by about 50%; bleeding risk rises moderately.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black stools, blood in urine. Severe cases include gastrointestinal or intracranial haemorrhage.
Management
The combination is acceptable in patients with preserved renal function (creatinine clearance above 50 mL/min) and atrial fibrillation. In renal impairment, switch to warfarin or apixaban.
Sources
Mechanism
Both drugs prolong QT. Amiodarone strongly (via IKr potassium channel block), sertraline dose-dependently and more weakly. Effects add up, especially at high sertraline doses (>100 mg/day) and risk factors: hypokalaemia, female sex, older age.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
The combination is acceptable at low sertraline doses (≤100 mg/day) and normal potassium and magnesium. ECG before start and at 2 weeks. Alternative antidepressants with minimal QT effect: mirtazapine or agomelatine.
Mechanism
Dual mechanism: amiodarone blocks CYP3A4 – a partial sildenafil metabolic route – and both drugs prolong QT. Sildenafil plasma levels rise 2- to 4-fold.
Symptoms
Sudden blood pressure drop: dizziness, syncope. QT prolongation on ECG with torsades de pointes risk. Visual disturbances.
Management
On amiodarone, cap sildenafil at 25 mg (instead of 50–100 mg) and limit to one dose every 48 hours. ECG before start and at 2 weeks; maintain potassium and magnesium.
Mechanism
Amiodarone moderately inhibits hepatic CYP3A4 – the primary clearance route for simvastatin. Simvastatin plasma levels rise 2- to 3-fold. The effect is weaker than with clarithromycin, but at simvastatin doses of 40 mg and above the risk becomes clinically significant. The caps simvastatin at 20 mg/day when used with amiodarone.
Symptoms
Pain and weakness in thigh, shoulder, and calf muscles. Dark urine, elevated creatine kinase on lab work. Symptoms typically emerge 2–4 weeks after starting or increasing the dose. Acute rhabdomyolysis is less common than with clarithromycin pairs.
Management
When amiodarone is required, prescribe simvastatin at no more than 20 mg/day. If the patient is already established on 40–80 mg, switch to pravastatin or rosuvastatin, which do not use CYP3A4. Check creatine kinase 4–6 weeks after the combination starts and whenever muscle symptoms appear.
Sources
Mechanism
Amiodarone blocks CYP3A4 and P-glycoprotein – two key tacrolimus clearance routes. Tacrolimus plasma levels rise 2- to 3-fold. Additional risk of additive QT prolongation.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
When combined, reduce tacrolimus by 30–50%; check trough (C0) at days 3 and 7. ECG before start and at 2 weeks; maintain potassium and magnesium. Alternative antiarrhythmic in transplant patients: a beta-blocker for rate control or catheter ablation.
Mechanism
Dual mechanism: tramadol weakly prolongs QT (additive with amiodarone) and lowers the seizure threshold. Amiodarone also blocks CYP2D6 – the main tramadol activation route – so analgesia weakens while serotonergic activity persists.
Symptoms
QT prolongation on ECG, palpitations, syncope. Seizures may occur, especially in patients with prior epilepsy. Weakened tramadol analgesic effect.
Management
Avoid the combination. For analgesia in patients on amiodarone, use paracetamol, NSAIDs (with caution in heart failure), or morphine/oxycodone (pure opioids without QT effect).
Mechanism
Dual mechanism. Venlafaxine (SNRI) prolongs QT at high doses. Amiodarone is a potent QT prolonger and also blocks CYP2D6 – the venlafaxine metabolic route. Venlafaxine plasma levels rise; QT effects add up.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antidepressants with minimal QT effect: mirtazapine or agomelatine. If venlafaxine is needed, cap at 75 mg/day; ECG before start and at 2 weeks.
Mechanism
Additive suppression of sinus node and atrioventricular (AV) conduction. Symptomatic bradycardia, sinoatrial and AV block have been reported.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall risk.
Management
Avoid the combination. In atrial fibrillation, choose one strategy: amiodarone for rhythm control, verapamil for rate control. Alternatives: a beta-blocker + digoxin or catheter ablation.
Mechanism
Amiodarone inhibits CYP3A4 — the enzyme responsible for budesonide metabolism. Oral budesonide levels may rise, increasing iatrogenic hypercortisolism risk in long-term therapy. Inhaled budesonide is minimally absorbed — the effect is weaker.
Symptoms
On long-term therapy: moon face, weight gain with fat redistribution, skin thinning, acne, muscle weakness, mood disturbance, hyperglycaemia.
Management
For inhaled budesonide (Symbicort, Pulmicort) plus amiodarone, no adjustment needed. On oral budesonide (Cortiment, Entocort) over 8 weeks, assess for hypercortisolism and consider dose reduction or switching to mesalazine (in Crohn's disease). Amiodarone alternative in atrial fibrillation: dronedarone (no CYP3A4 effect).
Mechanism
Additive bradycardia and QT effect from amiodarone, on top of carvedilol's negative chronotropy. Often used in heart failure with reduced ejection fraction and atrial fibrillation — an acceptable combination.
Symptoms
Bradycardia, dizziness, fatigue, near-syncope. QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Start carvedilol at minimum dose (3.125 mg twice daily) with up-titration every 2 weeks. Check ECG and heart rate at 1 and 4 weeks. If heart rate falls below 50 bpm or 2nd/3rd-degree AV block develops, adjust both. Keep potassium and magnesium in the upper half of normal range.
Sources
Mechanism
Celecoxib is a CYP2C9 substrate. Amiodarone weakly inhibits CYP2C9, so celecoxib AUC may rise moderately. Clinically significant amplification of celecoxib side effects is unlikely.
Symptoms
Possible typical celecoxib side effects: dyspepsia, peripheral oedema, BP rise. GI bleeding is rare.
Management
No dose adjustment needed. On long-term celecoxib, check BP and renal function every 3 months. Alternatives for rheumatologic pain: topical NSAIDs, paracetamol up to 2 g/day.
Mechanism
Amiodarone weakly inhibits CYP2C19, the key enzyme that converts clopidogrel to its active metabolite. Effect is clinically minimal; no proven reduction in antiplatelet activity.
Symptoms
The combination usually causes no specific symptoms. Baseline clopidogrel bleeding risk and amiodarone bradycardia risk remain.
Management
No dose adjustment needed. After acute coronary syndrome, if antiplatelet activity is in doubt, consider switching to ticagrelor or prasugrel (CYP2C19-independent).
Mechanism
Dexamethasone is a weak CYP3A4 inducer and may slightly reduce amiodarone levels in long-term therapy. The additive QT effect is minimal but persists in predisposed patients.
Symptoms
Short dexamethasone pulses usually cause no symptoms. QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short dexamethasone courses (3–7 days), no specific adjustment needed. For long-term therapy, check ECG every 3 months. In atrial fibrillation with uncontrolled rate, consider raising amiodarone by 50–100 mg/day.
Mechanism
No direct pharmacokinetic interaction. Additive bleeding risk in patients on concurrent warfarin or amiodarone (the latter enhances anticoagulation via CYP2C9 inhibition).
Symptoms
Epigastric pain, heartburn, black or tarry stools, gum bleeding, bruising. Higher risk in older patients and prior peptic ulcer disease.
Management
For short diclofenac courses (3–7 days), no specific adjustment needed. For long-term needs, consider paracetamol up to 2 g/day, topical NSAIDs, or physiotherapy. Avoid NSAIDs on a warfarin-amiodarone regimen.
Mechanism
Duloxetine is a CYP1A2 and CYP2D6 substrate. Amiodarone weakly inhibits CYP1A2 — duloxetine levels can rise. There is also an additive QT effect at high duloxetine doses (over 60 mg/day).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease. On high-dose duloxetine: nausea, insomnia, dry mouth, elevated blood pressure.
Management
On starting the combination, begin duloxetine at 30 mg/day. Check ECG at 1 and 2 weeks. In hypertension and tachycardia, do not exceed 60 mg/day. Antidepressant alternative without CYP1A2 or QT effect: sertraline.
Mechanism
Fluvoxamine is a strong CYP1A2 inhibitor and moderate CYP3A4 inhibitor. Levels of amiodarone and its active metabolite (desethylamiodarone) can rise, amplifying the QT effect.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. In depression and anxiety on amiodarone, alternatives: sertraline or escitalopram (the latter cautiously in older patients, cap at 10 mg). If unavoidable, start fluvoxamine at 25 mg/day and check ECG at 1 and 2 weeks.
Mechanism
Amiodarone contains 37% iodine in its structure. With iodine contrast (iopromide), total iodine load rises sharply, which can trigger amiodarone-induced thyrotoxicosis in predisposed patients (nodular goitre, autoimmune thyroiditis).
Symptoms
Palpitations, sweating, tremor, weight loss, anxiety, hyperthermia. Symptoms develop 1–3 months after contrast.
Management
Before elective contrast imaging on amiodarone, check TSH and T4. With normal thyroid function and nodular goitre, consider non-contrast alternatives (MRI without contrast). After imaging, check TSH at 1, 3, and 6 months. In thyrotoxicosis, stop amiodarone if feasible and start thiamazole plus prednisolone.
Mechanism
Linezolid mildly prolongs QT, additively with amiodarone. Clinically significant arrhythmia is rare, but risk is higher with hypokalaemia, hypomagnesaemia, and bradycardia.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short linezolid courses (10–14 days), check ECG before start and one week in. Keep potassium and magnesium in the upper half of the normal range. In atrial fibrillation with prior ventricular arrhythmia, alternatives: vancomycin or daptomycin.
Mechanism
Loratadine causes minimal QT prolongation at standard doses, but with CYP3A4 blockade by amiodarone, loratadine levels rise, potentially amplifying cardiac effects in predisposed patients.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Standard loratadine 10 mg/day is kept. In patients with prior QT prolongation, hypokalaemia, or bradycardia below 60 bpm, switch to cetirizine (minimal QT effect). Check ECG every 3–6 months on the combination.
Mechanism
No direct pharmacokinetic interaction. Cases of enhanced hepatotoxicity have been reported with long-term co-use, since both drugs can cause steatohepatitis and liver fibrosis.
Symptoms
Fatigue, nausea, jaundice, elevated liver enzymes. Symptoms develop with long-term therapy (over 6 months).
Management
On the combination, check ALT, AST, and alkaline phosphatase every 3 months. If enzymes rise 2–3-fold above the upper limit, repeat at 2 weeks; if persistently elevated, consider temporary methotrexate withdrawal. In rheumatoid arthritis, alternative: leflunomide (if no liver fibrosis).
Mechanism
Rosuvastatin is minimally metabolised by CYP3A4, so amiodarone's CYP3A4 inhibition has limited effect. A slight AUC rise is possible via OATP1B1 transport. Additive myopathy risk is modest.
Symptoms
Muscle pain, weakness, dark urine. Rhabdomyolysis with rosuvastatin and amiodarone is rare.
Management
No dose adjustment needed. Cap rosuvastatin at 20 mg/day with amiodarone. Check CK if muscle pain develops. Alternative: pravastatin (minimal interaction).
Mechanism
Amiodarone is a weak CYP3A4 inhibitor. Tamsulosin is a CYP3A4 and CYP2D6 substrate. Tamsulosin AUC rises moderately, amplifying orthostatic hypotension.
Symptoms
Postural dizziness, syncope, fatigue. In older patients: fall and fracture risk. Also possible: intraoperative floppy iris syndrome during cataract surgery.
Management
On starting amiodarone in a tamsulosin patient, check standing/sitting BP at 1 and 2 weeks. In older patients, do not exceed 0.4 mg/day of tamsulosin. Before cataract surgery, warn the ophthalmologist about tamsulosin (discontinuation 1–2 weeks before does not prevent floppy iris syndrome).
Mechanism
Amiodarone inhibits CYP1A2 and CYP3A4 — the key enzymes of theophylline metabolism. Theophylline levels may rise by 30–50%, raising toxicity risk.
Symptoms
Nausea, tachycardia, tremor, insomnia, severe cases: seizures. Symptoms appear at theophylline above 20 mcg/mL.
Management
On starting amiodarone in a theophylline patient, cut theophylline by 30% and check levels at 1–2 weeks (target 10–15 mcg/mL). Bronchodilator alternative: tiotropium or another long-acting muscarinic antagonist.
Mechanism
No clinically significant direct interaction. Montelukast is metabolised by CYP2C8 and CYP3A4; amiodarone moderately inhibits CYP3A4. Montelukast AUC may rise slightly, without clinical consequences.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. In asthma with atrial fibrillation, the combination is standard.
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Boxed warning
FDA boxed warning: amiodarone is for life-threatening recurrent ventricular arrhythmias refractory to other therapy. The drug causes potentially fatal pulmonary toxicity (fibrosis, pneumonitis), hepatotoxicity, and proarrhythmias. Use in less severe arrhythmias is justified only when benefit is clear and the patient is informed of the risks.
FDA categories retired in 2015 (historically category D). Amiodarone crosses the placenta and causes foetal hypothyroidism, goitre, bradycardia, and preterm birth. Use in pregnancy only on vital indications with no alternatives.
Excreted into breast milk in high concentrations; breastfeeding is contraindicated.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Amiodarone is evaluated for the following indications with varying evidence strength: Ventricular fibrillation and cardiac arrest (evidence tier A), Ventricular tachycardia (evidence tier A), Atrial fibrillation: rhythm control (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Amiodarone (≥ 1 in 100): Corneal microdeposits (over 90 % on long-term therapy, asymptomatic), Photosensitivity, bluish-grey skin pigmentation, Nausea, taste disturbance, Tremor, sleep disturbance, Transaminase elevation (15–30 %), Hypothyroidism and thyrotoxicosis. See the Safety section for uncommon and serious reactions.
FDA category D. FDA categories retired in 2015 (historically category D). Amiodarone crosses the placenta and causes foetal hypothyroidism, goitre, bradycardia, and preterm birth. Use in pregnancy only on vital indications with no alternatives.
Excreted into breast milk in high concentrations; breastfeeding is contraindicated.
Amiodarone is contraindicated in: Sinus bradycardia or second- or third-degree AV block without pacemaker; Sick sinus syndrome without pacemaker; Prolonged QT and congenital long QT syndrome; Severe thyroid dysfunction (uncontrolled hyperthyroidism); Hypersensitivity to iodine or amiodarone. Full list in the Safety section.
FDA boxed warning: amiodarone is for life-threatening recurrent ventricular arrhythmias refractory to other therapy. The drug causes potentially fatal pulmonary toxicity (fibrosis, pneumonitis), hepatotoxicity, and proarrhythmias. Use in less severe arrhythmias is justified only when benefit is clear and the patient is informed of the risks.
amiodarone's extracardiac toxicity profile is among the worst in cardiology. Prescribing requires routine monitoring of thyroid, lung, liver, and eyes.
half-life is 25–110 days. Drug effect and interactions persist for months after discontinuation. This affects surgery planning, switching warfarin to a DOAC, and starting other drugs.
the ALPS 2016 RCT showed that neither amiodarone nor lidocaine significantly improved survival to hospital discharge in cardiac arrest with shockable rhythm. They reduce in-hospital arrhythmia recurrence. High-quality CPR and early defibrillation remain decisive.