Amiodarone

Mechanism

Both drugs prolong the QT interval on the electrocardiogram: amiodarone through its main action (amiodarone SmPC), and amitriptyline commonly prolongs QT and widens the QRS complex (amitriptyline SmPC). Together they raise the risk of torsades de pointes. There is a second mechanism: amiodarone inhibits CYP2D6 (amiodarone SmPC), amitriptyline is cleared mainly by CYP2D6 and CYP2C19, and CYP2D6 inhibitors can markedly raise its levels (amitriptyline SmPC). Amiodarone is eliminated very slowly, so the interaction is possible for several months after it is stopped (amiodarone SmPC).

Symptoms

QT prolongation on the electrocardiogram (ECG) causes no symptoms by itself. Palpitations, dizziness or fainting may occur. The dangerous complication is torsades de pointes or other ventricular arrhythmias, sometimes fatal (amiodarone SmPC). Amiodarone can markedly slow the heart rate, especially in older people, and cause atrioventricular block (amiodarone SmPC). The risk of arrhythmia is higher with low potassium or magnesium, marked bradycardia, decompensated heart failure or heart disease (amitriptyline and amiodarone SmPCs).

Management

The combination is contraindicated: one of the Spanish amiodarone SmPCs contraindicates amiodarone with drugs that prolong the QT interval and names amitriptyline (amiodarone SmPC). The SmPC of the original amiodarone (Trangorex) says to avoid it with tricyclic antidepressants (amiodarone SmPC, Trangorex), and the label approved by the US Food and Drug Administration (FDA) says to avoid QT-prolonging drugs and names tricyclic antidepressants among them (amiodarone FDA label). The amitriptyline SmPC contraindicates amitriptyline in any heart block or rhythm disorder and does not recommend it with QT-prolonging drugs (amitriptyline SmPC). Before amiodarone is started, an electrocardiogram (ECG) is recorded and potassium is measured, and the ECG is monitored throughout treatment (amiodarone SmPC); low potassium, magnesium and calcium are corrected before the start (amiodarone FDA label). Amiodarone is eliminated over months, so the interaction is still possible after it is stopped (amiodarone SmPC).

Mechanism

Dual QT prolongation, additive hypotension (chlorpromazine alpha-1 block).

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated.

Mechanism

Amiodarone is a class III antiarrhythmic, and its SmPC describes QT prolongation as a direct pharmacological effect of the drug. Class IA and III antiarrhythmics open the list of examples in both SSRI labels. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Amiodarone washes out over weeks, so spacing the two drugs apart does not work: QT stays prolonged long after the last dose. Before any decision, potassium and magnesium are corrected and an ECG with QTc is recorded.

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 CYP3A4 and the P-glycoprotein transporter – two colchicine clearance routes. Colchicine plasma levels rise; myopathy and neuropathy risk grows.

Symptoms

The first signs of colchicine toxicity are nausea, vomiting, abdominal pain and diarrhoea (colchicine SmPC). Muscle weakness and pain, peripheral neuropathy with numbness and tingling in the feet and hands, and rhabdomyolysis may follow; with prolonged use, bone marrow suppression with falling white cells and platelets, up to aplastic anaemia (colchicine SmPC).

Management

The combination is contraindicated: the Spanish colchicine SmPC forbids colchicine during use of CYP3A4 or P-glycoprotein inhibitors and for 14 days afterwards (colchicine SmPC), and amiodarone inhibits both pathways (amiodarone SmPC). The US label of colchicine 0.5 mg for cardiovascular prevention, approved by the US Food and Drug Administration (FDA), also contraindicates it with P-glycoprotein inhibitors (colchicine label, FDA). Amiodarone interactions can persist for several months after it is stopped (amiodarone SmPC). Other colchicine manufacturers require a lower maximum colchicine dose and close monitoring with a P-glycoprotein inhibitor, and avoid the combination whenever possible in renal or hepatic impairment (colchicine SmPC). At the first sign of nausea, vomiting, abdominal pain or diarrhoea, colchicine is stopped and the patient needs urgent care (colchicine SmPC).

Mechanism

Amiodarone is the strongest clinical QT prolonger and CYP3A4 inhibitor. With disopyramide additive QT effect (each prolongs 30-50 ms).

Symptoms

QTc above 550 ms, syncope, torsades de pointes.

Management

Combination contraindicated. Choose one antiarrhythmic.

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 QT prolongation (amiodarone 30-50 ms, droperidol 10-20 ms). FDA boxed warning on droperidol.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated. Alternative – low-dose ondansetron or metoclopramide.

Mechanism

Amiodarone is a class III antiarrhythmic, and its SmPC describes QT prolongation as a direct pharmacological effect of the drug. Class IA and III antiarrhythmics open the list of examples in both SSRI labels. The escitalopram SmPC contraindicates any QT-prolonging drug alongside it: the ban is written broadly, and the classes in brackets are examples.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the escitalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. Amiodarone washes out over weeks, so spacing the two drugs apart does not work: QT stays prolonged long after the last dose. Before any decision, potassium and magnesium are corrected and an ECG with QTc is recorded.

Mechanism

Dual QT prolongation. Torsades de pointes cases reported.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated.

Mechanism

Additive QT prolongation from two strong QT prolongers + amiodarone inhibits CYP3A4 (methadone rises).

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated.

Mechanism

Additive QT prolongation (amiodarone 30-50 ms, pimavanserin 5-8 ms). FDA recommends avoiding.

Symptoms

QT above 500 ms, torsades de pointes.

Management

Combination contraindicated.

Mechanism

Amiodarone is a moderate CYP3A4 inhibitor and the strongest clinical QT prolonger. Double torsades risk. FDA Orap Section 4 + additive QT effect.

Symptoms

QT prolongation (amiodarone itself extends 30–50 ms), syncope, torsades de pointes.

Management

Combination contraindicated. For atrial fibrillation in a pimozide patient, use a beta-blocker for rate control or catheter ablation.

Mechanism

Dual QT prolongation (amiodarone extends 30–50 ms, quinidine 20–40 ms) plus amiodarone inhibits CYP3A4 (quinidine metabolism). FDA contraindication.

Symptoms

QTc above 500 ms, syncope, torsades de pointes.

Management

Combination contraindicated. Choose one antiarrhythmic – usually amiodarone in severe AF.

Mechanism

Dual mechanism: ritonavir strongly inhibits CYP3A4, the partial clearance route of amiodarone, raising amiodarone levels. Both drugs also prolong QT. The FDA 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

Both strongly prolong QT (amiodarone 30-50 ms, sotalol 30 ms). Additive prolongation – torsades de pointes.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated. Choose one antiarrhythmic.

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

Ziprasidone prolongs QT clinically (15-20 ms). With amiodarone – torsades de pointes.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Combination contraindicated.

Mechanism

Amiodarone inhibits CYP3A4, which takes part in atorvastatin metabolism, so atorvastatin levels can rise (amiodarone and atorvastatin labels). No interaction studies have been done for this pair, and the size of the effect is unknown (atorvastatin label). The risk of muscle damage, up to rhabdomyolysis, rises with statin exposure (amiodarone label). Because of amiodarone's long half-life, the interaction can persist for several months after it is stopped (amiodarone label).

Symptoms

Muscle pain, cramps or weakness, especially with fever and malaise, and raised creatine kinase. In severe cases rhabdomyolysis develops: creatine kinase above 10 times the upper limit of normal, myoglobin in blood and urine (dark urine) and possible kidney failure (atorvastatin label).

Management

The Spanish amiodarone label recommends using a statin that is not metabolized by CYP3A4 (amiodarone label). If atorvastatin is kept, consider a lower starting dose (FDA amiodarone label) and a lower maximum dose (atorvastatin label). Monitor the patient closely after amiodarone is started and after each dose change (atorvastatin label). Ask the patient to report muscle pain, cramps or weakness at once. If they appear, measure creatine kinase and stop atorvastatin if it is above 5 times the upper limit of normal (atorvastatin label). Amiodarone interactions persist for weeks to months after it is stopped (amiodarone labels).

Mechanism

Additive QT prolongation. Azithromycin received a 2013 FDA 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

Both drugs slow the heart rate and cardiac conduction. Bisoprolol is a selective beta-blocker (bisoprolol SmPC). Amiodarone blocks alpha and beta adrenoceptors non-competitively and slows conduction through the sinus and atrioventricular nodes (amiodarone SmPC). Together they increase bradycardia and conduction disorders (both SmPCs). Amiodarone is eliminated over months, so the interaction can persist for several months after it is stopped (amiodarone SmPC).

Symptoms

Marked bradycardia, dizziness, weakness, fainting. On the ECG: atrioventricular block of varying degree, sinoatrial block, and rarely sinus arrest. In older patients the heart rate can fall especially sharply (amiodarone SmPC).

Management

The amiodarone SmPC does not recommend combining it with beta-blockers because of the risk of marked bradycardia and conduction disorders. The bisoprolol SmPC lists the combination with amiodarone as one to use with caution. If a cardiologist still prescribes both, monitor the heart rate (US Food and Drug Administration (FDA) amiodarone label). Before amiodarone is started, record an ECG and check serum potassium (amiodarone SmPC). Stop amiodarone if second- or third-degree atrioventricular block, sinoatrial block or bifascicular block develops (amiodarone SmPC). In older patients the heart rate can fall especially sharply. The interaction can persist for several months after amiodarone is stopped, so keep checking the heart rate after that too (amiodarone SmPC).

Mechanism

Budesonide is broken down mainly by the CYP3A4 enzyme, and amiodarone and its metabolite inhibit this enzyme (amiodarone SmPC). Budesonide levels may rise, and with them the risk of systemic corticosteroid effects; these effects are less likely with inhaled than with oral budesonide (inhaled budesonide SmPC). A second mechanism involves systemic corticosteroids: they can lower potassium, and low potassium during amiodarone treatment raises the risk of torsades de pointes (amiodarone SmPC). Amiodarone is eliminated slowly, so interactions can occur for several months after it is stopped (amiodarone SmPC).

Symptoms

With long-term treatment: rounded face, weight gain with fat redistribution, thin skin, acne, muscle weakness, mood changes, raised blood glucose. If potassium falls during amiodarone treatment: palpitations, fainting, QT prolongation on the electrocardiogram (ECG) and, in severe cases, torsades de pointes.

Management

Oral budesonide should not be combined with CYP3A4 inhibitors unless the benefit outweighs the higher risk of systemic corticosteroid effects; if the combination is used, monitor the patient for these effects (oral budesonide SmPC). Amiodarone inhibits CYP3A4 (amiodarone SmPC), so this applies to it. The inhaled budesonide SmPC says to avoid strong CYP3A inhibitors and gives itraconazole, ketoconazole, human immunodeficiency virus (HIV) protease inhibitors and cobicistat-containing products as examples; amiodarone is not among them. With a 1–2 week course the interaction with inhaled budesonide is of limited relevance; in long-term treatment take it into account and watch for systemic effects (inhaled budesonide SmPC). Use amiodarone with caution alongside systemic corticosteroids: prevent and correct low potassium, monitor the QT interval, and do not give antiarrhythmic drugs if torsades de pointes occurs (amiodarone SmPC). Interactions with amiodarone can occur for several months after it is stopped (amiodarone SmPC).

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 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

The AEMPS label for carvedilol lists amiodarone among the drugs that raise the risk of atrioventricular conduction disturbances. 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.

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

Both drugs prolong the QT interval, and their effects on the heart add up, raising the risk of torsades de pointes (amiodarone SmPC). Clarithromycin inhibits CYP3A4, which clears amiodarone, so amiodarone levels may rise (amiodarone SmPC). The US Food and Drug Administration (FDA) also describes the reverse effect: amiodarone slows the clearance of macrolides other than azithromycin (amiodarone FDA label). Amiodarone is eliminated very slowly, and its interactions can persist for months after it is stopped (amiodarone SmPC).

Symptoms

QT prolongation on the electrocardiogram, palpitations, dizziness, fainting. In severe cases, torsades de pointes with a risk of ventricular fibrillation and sudden cardiac death. The risk is higher with low potassium or magnesium, marked bradycardia, coronary artery disease and in older patients.

Management

Avoid the combination. The US Food and Drug Administration (FDA) advises against clarithromycin in patients taking class III antiarrhythmics, including amiodarone (clarithromycin FDA label). The amiodarone FDA label advises avoiding certain macrolides with amiodarone, both as QT-prolonging drugs and as inhibitors of its metabolism (amiodarone FDA label). CYP3A4 inhibitors should be avoided during amiodarone treatment (amiodarone SmPC). QT-prolonging drugs, clarithromycin included, are combined with amiodarone only after a careful assessment of benefit and risk for the individual patient and with QT monitoring (amiodarone SmPC). Clarithromycin is contraindicated in patients with a history of QT prolongation or ventricular arrhythmia and in those with low potassium or magnesium (clarithromycin SmPC). The interaction remains possible for several months after amiodarone is stopped (amiodarone SmPC).

Mechanism

Amiodarone inhibits P-glycoprotein (P-gp), the efflux transporter for dabigatran. After a single 600 mg dose of amiodarone, dabigatran AUC rose about 1.6-fold and Cmax about 1.5-fold (EMA SmPC). Because amiodarone has a long half-life, the effect may persist for weeks after it is stopped.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black stools, blood in urine. Risk is higher in renal impairment.

Management

After elective hip or knee replacement, reduce dabigatran for thromboprophylaxis to 150 mg once daily (two 75 mg capsules); the EMA SmPC requires this for all patients on amiodarone. In atrial fibrillation and in treatment of deep vein thrombosis and pulmonary embolism, amiodarone does not call for a dose change (EMA SmPC; for atrial fibrillation also the FDA label). At creatinine clearance (CrCl) 30–50 mL/min, choose 110 mg twice daily individually based on bleeding risk (EMA SmPC). The FDA label says to avoid P-gp inhibitors at CrCl below 50 mL/min in deep vein thrombosis, pulmonary embolism and after hip replacement. Dabigatran is contraindicated at CrCl below 30 mL/min (EMA SmPC). Keep watching for signs of bleeding and anaemia for several weeks after amiodarone is stopped.

Mechanism

The point of contact is potassium, not cytochrome. The amiodarone label asks for caution with drugs that can cause hypokalaemia or hypomagnesaemia and names diuretics alone or in combination, systemic corticosteroids, tetracosactide and intravenous amphotericin B. In the same document: hypokalaemia alters the effects of amiodarone, increases QT prolongation and the risk of torsade de pointes. Dexamethasone is a potent systemic corticosteroid and produces that potassium loss. Its role as a weak CYP3A4 inducer is real but clinically counts for less than the electrolyte imbalance.

Symptoms

Palpitations, dizziness, presyncope and syncope. On ECG, a prolonged QTc and ventricular ectopy; torsade de pointes can degenerate into ventricular fibrillation. Muscle weakness, cramps and fatigue from low potassium usually come before the arrhythmia.

Management

Potassium and magnesium before dexamethasone starts in someone on amiodarone and during the course, correcting them first if already low. ECG with QTc at the start and at any rhythm symptom. The corticosteroid course is kept to the minimum indicated. If a potassium-wasting diuretic joins the pair, monitoring tightens, because the losses accumulate.

Mechanism

Amiodarone blocks P-glycoprotein in the intestine and renal tubules – the main 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

Both drugs slow the heart rate and conduction; together they can cause excessive bradycardia, sinus arrest and atrioventricular (AV) block (amiodarone labels in Spain and the US). There is also a pharmacokinetic part: CYP3A4 takes part in amiodarone metabolism and diltiazem moderately inhibits it. The Spanish amiodarone label advises avoiding CYP3A4 inhibitors because they can raise amiodarone levels, and the diltiazem label does not rule out higher diltiazem levels with amiodarone. Because of amiodarone's long half-life, interactions persist for weeks to months after it is stopped (amiodarone labels).

Symptoms

Slow pulse, sinus arrest and atrioventricular (AV) block (FDA amiodarone label). A slow pulse causes weakness and dizziness, and in severe cases fainting. The risk of bradycardia is higher in older patients and at high doses (diltiazem label).

Management

The Spanish amiodarone label does not recommend combining it with diltiazem because of the risk of excessive bradycardia and conduction disorders (amiodarone label). The Spanish diltiazem label requires strict clinical and ECG monitoring when it is combined with other antiarrhythmics, and caution with amiodarone, especially in older patients and at high doses (diltiazem label). If the combination cannot be avoided, adjust doses carefully and monitor heart rate (FDA amiodarone label) and the ECG (diltiazem label). Amiodarone interactions persist for weeks to months after it is stopped, so the same caution applies if diltiazem is started soon after amiodarone is withdrawn (amiodarone labels).

Mechanism

Fluconazole prolongs the QT interval on its own by blocking the cardiac Ikr potassium current. It is also a moderate CYP3A4 inhibitor, and amiodarone is partly cleared by CYP3A4, so, per the fluconazole label, the QT prolongation caused by amiodarone can be amplified. The risk is higher with high-dose fluconazole (800 mg a day).

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

ECG monitoring. If possible – terbinafine for superficial infections.

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.

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.

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) but needs monitoring. Check potassium and magnesium before starting and correct any deficit. Recheck potassium within the first week after indapamide is started (per the label) and more often than usual afterwards, because amiodarone prolongs the QT interval. Monitor the ECG and QT interval. If hypokalaemia cannot be controlled, replace indapamide with a drug that does not raise the risk of torsades de pointes.

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

Amiodarone inhibits CYP3A4. Lovastatin rises 2-3 fold. FDA recommends capping lovastatin at 40 mg/day with amiodarone.

Symptoms

Myalgia, weakness, dark urine, rising CK within 5-10 days.

Management

Cap lovastatin at 40 mg/day. Better – pravastatin or rosuvastatin.

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.

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

Ondansetron prolongs QT 10-15 ms, amiodarone 30-50 ms. Additive torsades risk.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Alternative – metoclopramide. If ondansetron needed – single IV dose no higher than 8 mg.

Mechanism

Additive AV node slowing and QT prolongation. Bradycardia, AV block.

Symptoms

Bradycardia below 50, AV block.

Management

Avoid combination. Choose one antiarrhythmic.

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

Both drugs prolong the QT interval. For amiodarone this is part of its main action: PR and QT intervals lengthen by about 10% (amiodarone label, US Food and Drug Administration, FDA). After quetiapine reached the market, QT prolongation was reported at therapeutic doses and in overdose (quetiapine SmPC). Together they raise the risk of torsades de pointes. Quetiapine is also cleared mainly by CYP3A4 (quetiapine SmPC), which amiodarone inhibits (amiodarone SmPC), so quetiapine levels may 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

The combination is avoided: the quetiapine label approved by the US Food and Drug Administration (FDA) names amiodarone among QT-prolonging drugs whose combination with quetiapine should be avoided, and the FDA amiodarone label advises against combining it with QT-prolonging drugs. The Spanish amiodarone SmPC allows the combination only after a careful benefit-risk assessment for the individual patient and with QT monitoring (amiodarone SmPC). Low potassium increases QT prolongation on amiodarone, so a potassium deficit is corrected (amiodarone SmPC). Quetiapine needs particular caution in older patients and in congenital long QT syndrome, heart failure, cardiac hypertrophy, low potassium or low magnesium (quetiapine SmPC). Amiodarone interactions can persist for several months after it is stopped (amiodarone SmPC).

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.

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 inhibits CYP3A4, the enzyme that metabolises simvastatin. In a study cited in the US simvastatin label (FDA), amiodarone 400 mg a day raised the AUC of simvastatin and its active acid form about 1.75-fold. Higher levels raise the risk of myopathy and rhabdomyolysis: in a clinical study, myopathy occurred in 6% of patients taking simvastatin 80 mg with amiodarone (simvastatin SmPC).

Symptoms

Muscle pain, tenderness or weakness with creatine kinase (CK) above 10 times the upper limit of normal. In rhabdomyolysis, urine turns dark from myoglobin and acute kidney injury may follow.

Management

The combination is not contraindicated, but the simvastatin dose is capped: no more than 20 mg a day, and higher doses with amiodarone are avoided (simvastatin SmPC). The US simvastatin and amiodarone labels (FDA) set the same limit. The amiodarone SmPC recommends a statin that is not metabolised by CYP3A4 during co-administration. Warn the patient about myopathy and ask them to report unexplained muscle pain, tenderness or weakness promptly (simvastatin SmPC).

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 and its metabolite inhibit the CYP3A4 enzyme and the P-glycoprotein transporter (amiodarone SmPC), and apixaban is cleared through both routes. Apixaban blood levels may rise, and with them the bleeding risk. There are no direct pharmacokinetic data for this pair (practical guide of the European Heart Rhythm Association, EHRA 2021). The apixaban SmPC of the European Medicines Agency (EMA) lists amiodarone among inhibitors expected to raise apixaban levels to a lesser degree than strong inhibitors. Because amiodarone is cleared slowly, interactions can persist for several months after it is stopped (amiodarone SmPC).

Symptoms

Gum bleeding, nosebleeds, bruising without trauma, blood in the urine or stool, heavy periods. Severe cases include gastrointestinal or intracranial bleeding. Risk is higher in older patients, with body weight 60 kg or less and with impaired kidney function (apixaban SmPC of the European Medicines Agency, EMA).

Management

The combination is allowed with caution. Do not change the apixaban dose because of amiodarone: the apixaban SmPC of the European Medicines Agency (EMA) requires no dose adjustment with inhibitors that are not strong and names amiodarone among them (apixaban SmPC, EMA). In atrial fibrillation, reduce apixaban to 2.5 mg twice daily only by its own criteria: two of three (age 80 years or older, body weight 60 kg or less, serum creatinine 133 µmol/L or higher) or creatinine clearance 15–29 mL/min (apixaban SmPC, EMA). The European Heart Rhythm Association (EHRA) advises caution, especially with polypharmacy. If at least one more risk factor is present (age 75 years or older, body weight 60 kg or less, chronic kidney disease, antiplatelet drugs, non-steroidal anti-inflammatory drugs, systemic steroids, previous bleeding, anaemia or low platelets, frailty or falls), EHRA suggests considering an anticoagulant with fewer interactions or replacing the other drug (EHRA 2021). The effect of amiodarone on other drugs lasts for several months after it is stopped, so caution is needed during that period too (amiodarone SmPC).

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

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 cleared by CYP1A2 and CYP2D6 (duloxetine label, US Food and Drug Administration, FDA). Amiodarone and its metabolite desethylamiodarone inhibit both enzymes (amiodarone SmPC), so duloxetine levels may rise. Amiodarone is not named as a potent CYP1A2 inhibitor: the duloxetine contraindication covers only fluvoxamine, ciprofloxacin and enoxacin (duloxetine SmPC). Duloxetine does not prolong the QT interval, even at 2.7–3.3 times the maximum dose (duloxetine label, FDA).

Symptoms

The combination may intensify the usual duloxetine adverse effects: nausea, headache, dry mouth, drowsiness and dizziness (duloxetine SmPC). Duloxetine can raise blood pressure, up to hypertensive crisis in patients with pre-existing hypertension (duloxetine SmPC). Duloxetine overdose has caused drowsiness, seizures, vomiting, tachycardia, serotonin syndrome and coma (duloxetine SmPC).

Management

The combination is acceptable with monitoring: the duloxetine SmPC asks for caution when it is given with drugs that impair its metabolism (duloxetine SmPC). In patients with heart disease, blood pressure is monitored, especially in the first month of duloxetine treatment, and a sustained rise calls for a lower duloxetine dose or gradual withdrawal (duloxetine SmPC). Amiodarone interactions can persist for several months after it is stopped (amiodarone SmPC).

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

Tamsulosin is broken down in the liver mainly by the CYP3A4 and CYP2D6 enzymes (tamsulosin labels). Amiodarone and its metabolite desethylamiodarone inhibit both enzymes and can raise the levels of their substrates (amiodarone SmPC); the US Food and Drug Administration (FDA) classifies amiodarone as a weak inhibitor of CYP3A4 and CYP2D6 (FDA table of CYP inhibitors). There are no data on how much tamsulosin levels rise with this combination. Tamsulosin itself can lower blood pressure, rarely to the point of fainting (tamsulosin SmPC), and higher levels may enhance this effect.

Symptoms

Dizziness and weakness on standing, rarely fainting (tamsulosin SmPC). In older patients, these episodes increase the risk of falls.

Management

Use tamsulosin with caution together with cytochrome P450 inhibitors, which include amiodarone (tamsulosin label of the US Food and Drug Administration, FDA). The FDA label stresses caution especially at doses above 0.4 mg a day; in Spain tamsulosin is taken as 0.4 mg once daily (tamsulosin SmPC). Warn the patient to sit or lie down at the first signs of orthostatic hypotension, such as dizziness or weakness, until they pass (tamsulosin SmPC).

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.