Amiodarone is an antiarrhythmic used for serious heart rhythm disorders that have not responded to other treatments. It is very effective, but can affect several organs (lungs, liver, thyroid, eyes, skin), so it requires close medical monitoring and regular tests/ECGs.
Also known as: Cordarone
Amiodarone raises plasma Digoxin levels, with risk of digitalis toxicity.
Amiodarone is a potent inhibitor of P-glycoprotein (P-gp), the transporter that eliminates digoxin at the intestinal, renal and biliary level. The inhibition reduces digoxin clearance and can raise its concentrations by 50–100%, with a risk of digitalis toxicity (nausea, arrhythmias, visual disturbances). The effect develops within days and persists for weeks after amiodarone is stopped (long half-life). The digoxin label recommends reducing the dose by about 30–50% when amiodarone is started and monitoring digoxin levels and the ECG. This combination is common in atrial fibrillation and requires tight control.
Amiodarone inhibits P-glycoprotein and can DOUBLE digoxin levels. Reduce the digoxin dose by 30–50% when starting and monitor digoxin levels.
Amiodarone inhibits P-glycoprotein and hepatic metabolism of Digoxin, potentially doubling its levels.
Digoxin levels from week 1 and symptom surveillance.
Nausea, yellow or blurred vision, bradycardia, arrhythmias.
Reduce the Digoxin dose (usually by half) and monitor serum levels.
DailyMed/FDA (NIH/NLM) — approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
High risk of QT prolongation and ventricular arrhythmias; the association should be avoided in most patients.
Chloroquine blocks cardiac potassium and sodium channels and prolongs the QT interval; with amiodarone the effect is additive and the risk of ventricular arrhythmias increases, especially with hypokalaemia, bradycardia or heart disease. In patients on chronic amiodarone (e.g. AF), prefer another antimalarial for acute malaria. If the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Chloroquine + amiodarone: additive QT prolongation with risk of torsades de pointes. Avoid the combination or monitor the ECG.
Additive effect on cardiac repolarisation (both Chloroquine and Amiodarone prolong QT via potassium channel blockade).
ECG (QTc), potassium and magnesium.
Syncope, palpitations, seizures.
Avoid the association; if unavoidable, ECG and electrolytes before and during, with maximum caution.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Additive QT prolongation with risk of ventricular arrhythmias.
Hydroxychloroquine blocks potassium channels (hERG) and prolongs the QT interval; with amiodarone the effect is additive and the risk of torsades de pointes increases, especially with hypokalaemia, bradycardia, renal impairment or heart disease. In patients on chronic amiodarone (e.g. AF) who need hydroxychloroquine (lupus, rheumatoid arthritis, malaria), prefer an alternative or monitor the ECG before and during treatment, correcting electrolytes.
Hydroxychloroquine + amiodarone: additive QT prolongation with risk of ventricular arrhythmias. Avoid or monitor the ECG.
Both prolong cardiac repolarisation.
ECG (QTc), potassium and magnesium.
Syncope, palpitations.
Avoid when possible; if needed, ECG and electrolytes.
DailyMed/FDA (NIH/NLM) — approved Hydroxychloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34496b43-05a2-45fb-a769-52b12e099341 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Increased risk of QT prolongation and ventricular arrhythmias.
Mefloquine prolongs the QT interval and is associated with ventricular arrhythmias and conduction blocks; with amiodarone the effect is additive. Both also affect AV conduction. In patients on chronic amiodarone needing malaria prophylaxis or treatment, prefer atovaquone+proguanil or doxycycline. If the combination is unavoidable, monitor the ECG and electrolytes and watch for proarrhythmia signs.
Mefloquine + amiodarone: additive QT prolongation with risk of ventricular arrhythmias. Avoid the combination.
Additive prolongation of cardiac repolarisation.
ECG (QTc) and electrolytes.
Palpitations, syncope.
Avoid; if unavoidable, monitor the ECG.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
High risk of QT prolongation and torsades de pointes.
Quinine prolongs the QT interval and inhibits CYP3A4, the main pathway of amiodarone metabolism, potentially raising its levels; the QT effect is additive and the torsades de pointes risk increases markedly. In patients on chronic amiodarone, prefer another antimalarial (atovaquone+proguanil, doxycycline). If the combination is unavoidable, monitor the ECG and electrolytes and reduce the amiodarone dose if needed.
Quinine + amiodarone: additive QT prolongation and CYP3A4 inhibition by quinine (amiodarone levels ↑). Avoid the combination.
Additive effect on cardiac potassium channel blockade.
ECG (QTc) and electrolytes.
Syncope, seizures, palpitations.
Avoid the association; if unavoidable, strict cardiac monitoring.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Rifampin markedly lowers Amiodarone levels — risk of arrhythmia recurrence.
Rifampicin is a potent inducer of CYP3A4 and P-glycoprotein and can reduce amiodarone (and active metabolite) concentrations by more than 50%, with loss of antiarrhythmic control. The effect persists for weeks after rifampicin discontinuation given the very long amiodarone half-life (up to 60 days). Avoid the combination when possible; if unavoidable, monitor the rhythm, consider adjusting (often increasing) the amiodarone dose and monitor the ECG.
Rifampicin + amiodarone: rifampicin strongly induces CYP3A4 and can reduce amiodarone levels to subtherapeutic. Avoid or monitor closely.
CYP3A4 induction, the main Amiodarone metabolic pathway.
ECG/rhythm, signs of arrhythmia recurrence.
Palpitations, syncope, tachycardia.
Avoid if possible; if unavoidable, monitor rhythm and consider an alternative.
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Voriconazole plus Amiodarone carries a risk of QT prolongation and ventricular arrhythmias.
Voriconazole is a moderate-to-potent CYP3A4 inhibitor and reduces amiodarone clearance, potentially raising its concentrations; both drugs prolong the QT interval, so the torsades de pointes risk increases additively. The combination should be avoided in patients with AF or other arrhythmias; if unavoidable (invasive aspergillosis in a patient on amiodarone), reduce the amiodarone dose, monitor the ECG and electrolytes and watch for adverse effects during and after antifungal treatment.
Voriconazole + amiodarone: voriconazole inhibits CYP3A4 and may raise amiodarone levels; both prolong the QT. Avoid the combination.
Additive effect on cardiac repolarization.
ECG (QT interval), electrolytes, signs of arrhythmia.
Syncope, palpitations, torsades de pointes.
Use with caution; monitor ECG (QT) and electrolytes (K+, Mg2+).
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Amiodarone + lithium: increased risk of ventricular arrhythmias with concomitant use (QUADRO 2).
Amiodarone (iodine-rich) can alter thyroid function and lithium also affects the thyroid; both have cardiac effects (bradycardia, QT prolongation, arrhythmias). QUADRO 2 of Annex 7 records this interaction in the amiodarone section. The combination may potentiate hypo- or hyperthyroidism and increase the arrhythmia risk, especially in the elderly. Lithium has a narrow therapeutic window and its levels must be monitored, along with TSH, ECG and electrolytes. Warn the patient of thyroid dysfunction symptoms (fatigue, cold/heat intolerance, palpitations) and of lithium toxicity signs (tremor, confusion).
Amiodarone + lithium: risk of thyroid toxicity and synergy in cardiotoxicity — monitor thyroid function, lithium levels and ECG.
QUADRO 2 lists lithium among the drugs that increase the risk of ventricular arrhythmias with concomitant amiodarone use (additive QT prolongation).
Monitor ECG (QT interval) and signs of arrhythmia.
Palpitations, syncope, ventricular arrhythmias in a patient on amiodarone + lithium.
Use with caution; monitor ECG and electrolytes in the combination.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Amiodarone)
Amiodarone + sotalol: increased risk of ventricular arrhythmias when two QT-prolonging antiarrhythmics are combined (QUADRO 2).
Amiodarone and sotalol prolong the QT interval by different mechanisms and the effect is additive: amiodarone blocks multiple potassium currents and sotalol blocks the IKr current, both increasing the risk of torsades de pointes and ventricular fibrillation. QUADRO 2 of Annex 7 flags amiodarone on the list of drugs that increase arrhythmia risk when combined with other antiarrhythmics. The combination arises mainly in structural heart disease, where any proarrhythmia is particularly dangerous. Whenever possible only one of the drugs should be maintained; if the combination is clinically and absolutely necessary, the ECG should be monitored (QTc interval), as well as potassium and magnesium, and correctable risk factors (hypokalaemia, bradycardia, QT-prolonging drugs) eliminated. Amiodarone has a very long half-life, so the risk persists for weeks after discontinuation.
Amiodarone + sotalol: combination of two QT-prolonging antiarrhythmics — high risk of ventricular arrhythmias; avoid and prefer monotherapy.
Amiodarone and sotalol prolong the QT interval — additive effect with risk of ventricular arrhythmias (incl. torsades de pointes) (QUADRO 2, Amiodarone: "Increased risk of ventricular arrhythmias with concomitant use: ... Sotalol").
Monitor ECG (QT interval), potassium and magnesium.
Syncope, palpitations, torsades de pointes in a patient on amiodarone + sotalol.
Avoid combining QT-prolonging antiarrhythmics; if unavoidable, cardiac monitoring with ECG and electrolytes.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Amiodarone)
Combining Levofloxacin with Amiodarone increases the risk of QT prolongation and ventricular arrhythmias (e.g. torsades de pointes).
Levofloxacin (fluoroquinolone) prolongs the QT interval by blocking the IKr current, and amiodarone prolongs it by multiple mechanisms: the combination is additive and may precipitate torsades de pointes, especially in patients with heart disease, hypokalaemia or bradycardia. QUADRO 2 of Annex 7 lists levofloxacin among the drugs that increase arrhythmia risk in patients taking amiodarone. Levofloxacin is often used in respiratory and urinary infections, where other classes (beta-lactams, lower-risk macrolides, nitrofurantoin) may be safe alternatives. If no alternative exists, the ECG should be monitored during the antibiotic with prompt electrolyte correction; amiodarone accumulates in tissue and the risk persists for weeks after levofloxacin discontinuation.
Amiodarone + levofloxacin: additive QT prolongation with risk of ventricular arrhythmias — avoid the combination and choose an alternative antibiotic.
Levofloxacin prolongs the ECG QT interval and Amiodarone is a class III antiarrhythmic with an additive effect; together they raise the risk of serious ventricular arrhythmias.
Monitor the ECG (QT interval), electrolytes (potassium/magnesium) and symptoms such as palpitations or syncope.
Syncope, palpitations, a very prolonged QT or arrhythmia require discontinuation and urgent evaluation.
Avoid the combination in patients at risk (hypokalemia, long QT, bradycardia); if unavoidable, monitor the ECG.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Amiodarone)
Amiodarone raises flecainide and both prolong the QT.
Flecainide is metabolised by CYP2D6; amiodarone inhibits this enzyme and also CYP2C9 and P-glycoprotein, potentially increasing flecainide concentrations by 50–100%. As both drugs depress conduction (widen QRS) and amiodarone prolongs QT, the proarrhythmia risk (ventricular tachycardia, blocks) increases. When the combination is needed (e.g. AF), reduce the flecainide dose by half, monitor the ECG (QRS, QT) and flecainide plasma levels if available.
Flecainide + amiodarone: amiodarone inhibits CYP2D6 and may double flecainide levels (proarrhythmia risk). Reduce the flecainide dose by 50% and monitor the ECG.
Amiodarone inhibits flecainide metabolism (CYP2D6/CYP3A4) and adds class III QT effect.
ECG (QT, QRS), proarrhythmia signs.
Torsades de pointes, syncope, worsening heart failure.
Reduce flecainide and monitor the ECG; avoid if baseline QT is long.
DailyMed (FDA) — approved Flecainide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=74c1eb2a-a37f-4f33-86bf-51e0d1d0c2bc ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Beta-blocker + antiarrhythmic: risk of severe bradycardia and AV block.
Both reduce AV conduction and heart rate. The combination can cause severe bradycardia, AV block, and cardiac arrest.
DailyMed/FDA (NIH/NLM) — approved Metoprolol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5466243e-1e3d-175e-e063-6394a90a5dee
Statin + antiarrhythmic: increased risk of myopathy.
Amiodarone may increase simvastatin levels. Maximum simvastatin dose: 20 mg/day with amiodarone.
DailyMed/FDA (NIH/NLM) — approved Simvastatin (Zocor) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8f55d5de-5a4f-4a39-8c84-c53976dd6af9
Epinephrine + antiarrhythmic: risk of ventricular arrhythmias.
Amiodarone prolongs the QT interval and ventricular repolarisation, and epinephrine, by stimulating beta and alpha receptors, increases automaticity and myocardial oxygen demand. Together they raise the risk of ventricular tachycardias and extrasystoles, especially in emergencies (cardiac arrest, anaphylaxis) or ischaemic heart disease. Hypokalaemia further favours arrhythmias. Monitor the ECG, correct electrolytes (potassium and magnesium) and use the lowest effective epinephrine doses.
Epinephrine + amiodarone: increased risk of ventricular arrhythmias and tachycardia (amiodarone prolongs QT and epinephrine increases automaticity). Use with caution and monitor ECG.
Adrenergic stimulation adds to drugs that prolong repolarisation, increasing arrhythmia risk.
ECG and blood pressure.
Palpitations, tachycardia, ventricular arrhythmias.
Use with caution in cardiac patients; monitor heart rhythm.
DailyMed (FDA) — approved Epinephrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5726eeca-db88-ba8e-e063-6294a90a927d ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Dabigatran + amiodarone: amiodarone increases dabigatran exposure (P-gp inhibitor) — QUADRO 2 recommends reducing the anticoagulant dose.
Dabigatran etexilate is a P-glycoprotein (P-gp) substrate and amiodarone is a P-gp inhibitor, increasing dabigatran bioavailability and plasma concentrations. QUADRO 2 of Annex 7 records this combination among oral anticoagulants with increased bleeding risk. The exposure increase is clinically relevant (in the range of 12-60% depending on the study), especially in the elderly, low body weight or renal impairment, where dabigatran already accumulates renally. In patients with creatinine clearance 30-50 ml/min, consider reducing dabigatran to 110 mg twice daily when combined with amiodarone. Watch for bleeding signs and reassess renal function periodically.
Dabigatran + amiodarone: amiodarone inhibits P-glycoprotein and increases dabigatran exposure — bleeding risk; consider dose reduction and surveillance.
Amiodarone interferes with P-glycoprotein (P-gp) responsible for dabigatran efflux, increasing its plasma concentrations and the bleeding risk (QUADRO 2, Oral anticoagulants: "Dabigatran: Increased bleeding risk from increased exposure... Amiodarone... the anticoagulant dose should be reduced").
Watch for signs of bleeding; assess renal function (the reduction is more relevant in renal impairment).
GI bleeding, haematuria, bleeding in a patient taking dabigatran + amiodarone.
Reduce the dabigatran dose when co-administered with amiodarone (follow label dose adjustment recommendations).
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Oral anticoagulants)
Amiodarone potentiates Warfarin's anticoagulant effect, raising INR and bleeding risk.
Amiodarone is a potent inhibitor of CYP2C9, the isoenzyme that metabolises S-warfarin (the more active enantiomer), and also inhibits CYP2C19 and CYP3A4. The result is a marked rise in the INR, which can start within the first days but continues to evolve for weeks because amiodarone has a very long half-life (20–100 days) and accumulates in tissues. The approved label recommends reducing the warfarin dose by 30–50% when amiodarone is started and monitoring the INR closely; the effect persists for weeks to months after amiodarone is stopped, so warfarin must be re-adjusted during that phase. This combination is common in atrial fibrillation patients and demands disciplined INR control and vigilance for bleeding.
Amiodarone inhibits CYP2C9 (and CYP2C19/CYP3A4) and can more than double the INR. Reduce warfarin by 30–50% when starting, monitor INR weekly, and re-adjust after amiodarone is stopped (prolonged effect, half-life of weeks).
Inhibits CYP2C9, the main enzyme metabolising Warfarin.
Weekly INR in the first weeks after starting Amiodarone.
Unusual bleeding, spontaneous bruising, gum bleeding.
Reduce the Warfarin dose by 25–50% and monitor INR more frequently.
DailyMed/FDA (NIH/NLM) — approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Both prolong the QT interval; the combination raises the risk of ventricular arrhythmias (e.g. torsades de pointes), especially with long QT, hypokalaemia or heart disease.
Both amiodarone and lumefantrine prolong the QT interval by blocking potassium channels (IKr). The additive effect increases the risk of torsades de pointes and sudden death, especially in patients with a prolonged baseline QT, hypokalaemia, bradycardia or structural heart disease. Whenever possible, prefer an antimalarial without QT effects (e.g. atovaquone+proguanil). If the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Artemether+lumefantrine + amiodarone: additive QT prolongation with risk of torsades de pointes. Avoid the combination or monitor the ECG closely.
Additive effect on cardiac repolarisation: Lumefantrine blocks potassium channels (hERG) and Amiodarone prolongs QT and is arrhythmogenic on its own.
ECG with QTc measurement, potassium and magnesium; closer monitoring in patients with risk factors.
Syncope, palpitations, dizziness, seizures.
Avoid whenever possible. If unavoidable, use with caution, correct hypokalaemia/hypomagnesaemia and monitor the ECG.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Amiodarone adds to Amodiaquine's QT-prolonging effect — risk of ventricular arrhythmias.
Amodiaquine blocks the IKr channel and prolongs the QT interval; combined with amiodarone (which also prolongs QT and inhibits CYP3A4, potentially raising amodiaquine levels), the risk of ventricular arrhythmias, including torsades de pointes, increases additively. In patients on chronic amiodarone, prefer an antimalarial without QT effects. If the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia.
Artesunate+amodiaquine + amiodarone: additive QT prolongation (amodiaquine). Avoid, or monitor ECG if unavoidable.
Additive prolongation of cardiac repolarisation.
ECG (QTc), potassium and magnesium.
Palpitations, syncope.
Prefer to avoid; if unavoidable, monitor ECG and electrolytes.
WHO — WHO Guidelines for malaria: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria ; DailyMed/FDA (NIH/NLM) — approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Bedaquiline prolongs the QT interval; combining with Amiodarone raises the risk of ventricular arrhythmias.
Bedaquiline prolongs the QT interval (hERG blockade) and amiodarone prolongs it too; the effect is additive and the risk of torsades de pointes increases, especially with hypokalaemia, hypomagnesaemia or heart disease. Amiodarone also inhibits CYP3A4, the pathway by which bedaquiline is metabolised, potentially raising its levels and worsening QT prolongation. Avoid the combination in multidrug-resistant tuberculosis whenever an alternative exists; if unavoidable, monitor the ECG (ideally weekly) and electrolytes.
Bedaquiline + amiodarone: additive QT prolongation with risk of torsades de pointes. Avoid the combination; if unavoidable, monitor the ECG weekly.
Additive cardiac repolarisation prolongation.
ECG (QTc), potassium and magnesium.
Syncope, palpitations.
Avoid; if unavoidable, periodic ECG and electrolyte control.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Ketoconazole plus Amiodarone carries a risk of QT prolongation and ventricular arrhythmias.
Amiodarone is metabolised by CYP3A4 and CYP2C8; ketoconazole is a potent CYP3A4 inhibitor and reduces amiodarone clearance, potentially doubling its concentrations. Since both also prolong the QT interval, the risk of torsades de pointes and of toxicity (pulmonary, hepatic, thyroid, neuropathy) increases. The combination should be avoided; if unavoidable, reduce the amiodarone dose, monitor the ECG and plasma levels (if available) and watch for adverse effects.
Ketoconazole + amiodarone: ketoconazole inhibits CYP3A4 and may raise amiodarone levels, increasing the QT/arrhythmia risk. Avoid the combination.
Additive effect on cardiac repolarization; ketoconazole may also raise amiodarone levels via metabolic inhibition.
ECG (QT interval), electrolytes (K+, Mg2+), signs of arrhythmia/palpitations.
Syncope, palpitations, torsades de pointes.
Use with caution; monitor ECG (QT interval) and electrolytes (K+, Mg2+); correct hypokalaemia before combining.
DailyMed/FDA (NIH/NLM) — approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Piperaquine prolongs QT; combining with Amiodarone raises the risk of ventricular arrhythmias (e.g. torsades de pointes).
Piperaquine markedly prolongs the QT interval (hERG blockade) and has been associated with torsades de pointes, especially in combination with other QT-prolonging drugs such as amiodarone. The risk is higher with a prolonged baseline QT, hypokalaemia, hypomagnesaemia or heart disease. In patients on chronic amiodarone, prefer an antimalarial without QT effects. If the combination is unavoidable, monitor the ECG and electrolytes and avoid other risk factors.
Dihydroartemisinin+piperaquine + amiodarone: additive QT prolongation (piperaquine). Avoid the combination or monitor the ECG.
Additive effect on cardiac repolarisation.
ECG (QTc), potassium and magnesium.
Syncope, palpitations, seizures.
Avoid; if unavoidable, strict cardiac monitoring (ECG and electrolytes).
EMA — EPAR Eurartesim (dihydroartemisinin + piperaquine): https://www.ema.europa.eu/en/medicines/human/EPAR/eurartesim ; DailyMed/FDA (NIH/NLM) — approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Combining Phenytoin with Amiodarone increases Phenytoin concentrations and may cause signs of toxicity.
The interaction is bidirectional: phenytoin induces CYP3A4 and lowers amiodarone (and active metabolite) concentrations, potentially reducing the antiarrhythmic effect; conversely, amiodarone inhibits CYP2C9 and epoxide hydrolase, potentially doubling phenytoin levels and causing toxicity (nystagmus, ataxia, lethargy). Changes develop over weeks because of the very long amiodarone half-life. Monitor phenytoin plasma levels, adjust the dose and watch for amiodarone efficacy.
Phenytoin + amiodarone: phenytoin lowers amiodarone levels (CYP3A4 induction) and amiodarone raises phenytoin levels (CYP2C9 inhibition). Monitor both.
Amiodarone inhibits Phenytoin metabolism, raising its serum levels; Phenytoin may in turn lower Amiodarone levels.
Watch for signs of Phenytoin toxicity: nystagmus, ataxia, diplopia, sedation.
Nystagmus, ataxia or signs of Phenytoin toxicity require level testing and adjustment.
Monitor serum Phenytoin concentrations and adjust the dose; watch the cardiac effects of Amiodarone.
DailyMed/FDA (NIH/NLM) — approved Phenytoin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ef4e97a7-cd18-47a9-a016-2eca5481a87e ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Itraconazole plus Amiodarone carries a risk of QT prolongation and ventricular arrhythmias.
Itraconazole is a potent CYP3A4 inhibitor, the main pathway of amiodarone metabolism; coadministration can substantially raise amiodarone concentrations. As both prolong the QT interval, the risk of torsades de pointes and of amiodarone toxicity (pulmonary, hepatic, thyroid) increases. The combination should be avoided; if unavoidable, reduce the amiodarone dose, monitor the ECG and watch for adverse effects during antifungal treatment and after its discontinuation.
Itraconazole + amiodarone: itraconazole inhibits CYP3A4 and may raise amiodarone levels, with QT/arrhythmia risk. Avoid the combination.
Additive effect on cardiac repolarization; itraconazole may also raise amiodarone levels.
ECG (QT interval), electrolytes (K+, Mg2+), signs of arrhythmia.
Syncope, palpitations, torsades de pointes.
Use with caution; monitor ECG (QT) and electrolytes (K+, Mg2+); correct hypokalaemia before combining.
DailyMed/FDA (NIH/NLM) — approved Itraconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d555fa-787c-40fb-bb7d-b0d4f7318fd0 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Sympathomimetic decongestant + antiarrhythmic: risk of arrhythmias and pressor effect.
Pseudoephedrine is a sympathomimetic that increases heart rate and automaticity; in patients treated with amiodarone (which prolongs QT and is frequently associated with underlying heart disease), the risk of tachycardias and ventricular extrasystoles increases. Pseudoephedrine should be avoided in patients with known arrhythmias or ischaemic heart disease; if used, limit the duration, watch for symptoms (palpitations, chest pain) and prefer non-sympathomimetic alternatives (e.g. nasal corticosteroids, antihistamines) for nasal congestion.
Pseudoephedrine + amiodarone: the sympathomimetic effect of pseudoephedrine increases the arrhythmia risk in patients on amiodarone. Avoid or use with caution.
Pseudoephedrine (α-agonist) raises blood pressure and cardiac work, risking arrhythmia in predisposed patients.
Blood pressure and ECG.
Hypertension, tachycardia, arrhythmias.
Avoid in cardiovascular disease; if used, monitor BP and rhythm.
DailyMed (FDA) — approved Pseudoephedrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78faa497-6743-b85b-e053-2a91aa0ae822 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Rifabutin lowers Amiodarone levels — risk of arrhythmia recurrence.
Rifabutin induces CYP3A4 and lowers amiodarone plasma concentrations (and its active metabolite), potentially compromising arrhythmia control. The interaction develops over days to weeks and persists after rifabutin discontinuation (long amiodarone half-life). Monitor the rhythm and clinical response, consider adjusting the amiodarone dose and monitor the ECG during and after rifabutin treatment.
Rifabutin + amiodarone: rifabutin induces CYP3A4 and lowers amiodarone levels, potentially reducing antiarrhythmic efficacy. Monitor the clinical effect.
CYP3A4 induction.
ECG and rhythm.
Palpitations, syncope.
Monitor rhythm; consider an alternative.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Amiodarone + atorvastatin: amiodarone decreases statin metabolism, increasing the risk of myopathy/rhabdomyolysis (QUADRO 2).
Amiodarone inhibits CYP3A4, the pathway that metabolises atorvastatin (and simvastatin/lovastatin), increasing their plasma concentrations and the risk of myopathy and rhabdomyolysis. QUADRO 2 of Annex 7 records this interaction in the HMG-CoA reductase inhibitor section. The risk is higher with high statin doses, the elderly, hypothyroidism or renal impairment. If the combination is necessary, use atorvastatin at the lowest effective dose (or prefer pravastatin/rosuvastatin, less dependent on CYP3A4) and instruct the patient to report myalgia, weakness or dark urine. Monitor CPK if muscle symptoms appear.
Amiodarone + atorvastatin: CYP3A4 inhibition — increased statin and risk of myopathy/rhabdomyolysis; reduce statin dose.
Amiodarone inhibits CYP3A4 which metabolises atorvastatin — increased concentrations and myopathy risk (QUADRO 2, HMG-CoA reductase inhibitors: "Drugs that decrease statin metabolism: Amiodarone").
Monitor CK and muscle symptoms (myalgia, weakness, dark urine).
Severe myalgia, rhabdomyolysis in a patient on amiodarone + atorvastatin.
Use the lowest effective atorvastatin dose (≤ 20 mg) and watch for muscle symptoms.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (HMG-CoA reductase inhibitors)
Acenocoumarol + amiodarone: amiodarone increases the anticoagulant effect of acenocoumarol, with bleeding risk — monitor INR when starting or stopping amiodarone.
QUADRO 2 of Annex 7 (Warfarin) lists amiodarone among drugs that increase the anticoagulant effect with bleeding risk; acenocoumarol refers to warfarin ("Acenocoumarol: see Warfarin"), sharing the coumarin interaction profile. Amiodarone inhibits coumarin metabolism (CYP2C9) and displaces them from plasma proteins, and the effect persists for weeks after discontinuation due to amiodarone's long half-life.
Monitor INR 3-7 days after starting, adjusting or stopping amiodarone, and periodically thereafter.
Markedly elevated INR, bleeding or spontaneous bruising after starting amiodarone.
When starting amiodarone in a patient stabilized on acenocoumarol, reduce the anticoagulant dose (typically 30-50%) and titrate by INR; when stopping amiodarone, reassess the dose.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, Table 2 (Oral anticoagulants: Acenocoumarol — see Warfarin; Amiodarone)
Degarelix + amiodarone: risk of QT interval prolongation — evaluate the combination carefully.
The Prontuário documents for degarelix that "concomitant use with drugs that prolong the QTc interval should be carefully evaluated (e.g. class Ia and III antiarrhythmics, methadone, moxifloxacin and some antipsychotics)". Amiodarone, a class III antiarrhythmic, prolongs the QT interval in a well-known manner and adding it to degarelix increases the risk of ventricular arrhythmias, including torsades de pointes. The risk is higher in patients with prolonged baseline QT, hypokalaemia, hypomagnesaemia, advanced age or renal/hepatic impairment. If the combination is unavoidable, monitor the ECG and electrolytes and prefer the shortest possible duration; any syncope or palpitation must be assessed urgently.
Degarelix + amiodarone: assess QT prolongation risk — prefer an alternative if possible.
The Prontuário documents for degarelix: "Concomitant use with drugs that prolong the QTc interval should be carefully evaluated (e.g. class Ia and III antiarrhythmics...)". Amiodarone (class III) prolongs QT and the combination adds arrhythmia risk (torsades de pointes).
ECG and electrolytes (potassium, magnesium) before and during the combination in at-risk patients.
Syncope, palpitations, dizziness or prolonged QT on ECG during the combination.
Assess individual risk (baseline QT, electrolytes, age, renal/hepatic function); prefer alternatives without QT effect when possible; if unavoidable, monitor the ECG.
DailyMed/FDA (NIH/NLM) — approved Degarelix label (FIRMAGON): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab11dd8a-0fd9-4013-89ab-e114557c7e4b ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Degarelix, 16.2.2.5
Amiodarone can be taken with or without food; consistent intake reduces level variability.
Always take it the same way (with or without food).
DailyMed/FDA (NIH/NLM) — approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c149392-a4f0-4e2d-a13f-2b94810005de
Grapefruit inhibits CYP3A4 and may raise amiodarone concentrations, increasing the risk of QT prolongation and arrhythmias.
Avoid grapefruit juice during treatment.
DailyMed/FDA (NIH/NLM) — approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c149392-a4f0-4e2d-a13f-2b94810005de
Amiodarone may cause interstitial lung disease or pulmonary fibrosis, sometimes fatal; it is contraindicated in active interstitial lung disease.
Do not use; monitor for cough and dyspnoea and obtain a chest X-ray on any suspicion.
EMC-UK (MHRA) — approved Amiodarone SmPC: https://www.medicines.org.uk/emc/product/8739/smpc
Amiodarone is contraindicated in pregnancy: it contains iodine and may cause fetal thyroid dysfunction and other toxicities.
Do not use in pregnancy; consider alternative antiarrhythmic therapy.
Contraindicated during breastfeeding because of the risk of thyroid toxicity in the infant.
Women of childbearing age must use effective contraception during treatment.
EMC-UK (MHRA) — approved Amiodarone SmPC: https://www.medicines.org.uk/emc/product/8739/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: Avoid, because significant amounts are present in milk; possible hypothyroidism.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Antiarrhythmic with class I, II, III and IV properties. The oral antiarrhythmic effect takes 2 days to 3 weeks to develop and, because of the very long half-life, effects and interactions may persist for weeks to months after discontinuation. The time to arrhythmia recurrence after stopping is variable and unpredictable.
Prolongs phase 3 of the action potential (class III) by blocking potassium channels, with QT interval prolongation; it also blocks sodium channels (class I), has non-competitive beta-blockade (class II) and calcium channel blockade (class IV). It produces coronary and peripheral vasodilatation and reduces heart rate.
After oral administration, peak plasma concentrations occur in 3 to 7 hours. Food increases the rate and extent of absorption: AUC and Cmax increase about 2.3 and 3.8 times, respectively, when taken with a high-fat meal. Oral bioavailability is incomplete and variable.
Metabolised in the liver, mainly by CYP3A4 and CYP2C8, with formation of the active metabolite desethylamiodarone. Elimination is very slow, with extensive tissue accumulation (fat, liver, lung).
The half-life of amiodarone is 15 to 142 days and that of the active metabolite desethylamiodarone 14 to 75 days, which explains why effects and interactions persist for weeks after discontinuation.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
