Table 15.
Key drugs with potential interactions involving AADs, excluding anticoagulants (covered in Table 21) and AAD combinations (discussed in Table 16)
| Modified VW class | AAD | Drug #1 | Advice for concurrent use with drug #1 | Drug #2 | Advice for concurrent use with drug #2 |
|---|---|---|---|---|---|
| 0 | Ivabradine | Strong CYP3A4 inhibitorsa (+ivabradine) | Avoid combination | CYP3A4 inducersb (−ivabradine) | Avoid combination |
| Ia | Quinidine | Strong CYP3A4 inhibitorsa (+quinidine) | Caution, monitor levels | Other QT-prolonging drugs | Avoid combination |
| Procainamide | Cimetidine, propranolol, verapamil (+procainamide) | Replace (e.g. cimetidine by PPIs), monitor procainamide levels | Amiodarone (+procainamide, summative effect) | Monitor ECG | |
| Disopyramide | Anti-cholinergic (H1-anti-histaminics, anti-spasmodics, tricyclic anti-depressants) (summative) | Avoid combination | β-Blockers, CCB (additive negative inotropic effect) | Monitor cardiac function | |
| Ib | Lidocaine | Amiodarone, β-blockers, cimetidine (+lidocaine) | Replace (e.g. PPIs, renal excreted β-blockers), reduce lidocaine dose or monitor levels | β-Blockers (+lidocaine) | Reduce lidocaine dose |
| Mexiletine | Theophylline (+theophylline) | Reduce and monitor theophylline levels | Phenytoin (mutual reduction) | Adjust dose, monitor levels | |
| Phenytoin | CYP3A4 inhibitorsa (+phenytoin) | Reduce phenytoin dose, monitor phenytoin levels | Oral contraceptives (reduces contraceptive efficacy) and corticosteroid (reduces efficacy) | Avoid or increase corticosteroid dose | |
| Ic | Flecainide | Digoxin (+digoxin) | Reduce digoxin dose (25%), monitor digoxin levels | Amiodarone, Fluoxetine/paroxetine (+flecainide) | Replace (e.g. escitalopram or sertraline), reduce (30%) flecainide dose, monitor levels and ECG |
| Propafenone | Digoxin (+digoxin) | Reduce digoxin dose (25%), monitor digoxin levels | Fluoxetine/paroxetine (+propafenone) | Replace (e.g. escitalopram or sertraline), reduce (30%) flecainide dose, monitor levels and ECG | |
| Id | Ranolazine | Strong CYP3A4 inhibitorsa (+ranolazine) | Avoid combination | Statins (potentiates myopathy) | Limit statin dose or use non-CYP3A4 statins (pitavastatin, pravastatin, rosuvastatin) |
| IIa | β-Blockers | Anti-diabetic drugs (mask hypoglycaemic symptoms) | Counsel patients, avoid non-selective β-blockers (use carvedilol or nebivolol) | Clonidine (hypertension if abrupt discontinuation) | Avoid abrupt clonidine discontinuation |
| IId | Digitalis | Amiodarone/dronedarone/flecainide/propafenone/quinidine/ranolazine/verapamil (+digoxin) | Reduce (50%) or avoid digoxin, monitor digoxin levels | Macrolides (+digoxin) | Monitor digoxin levels |
| IIe | Adenosine | Dipyridamole (potentiates adenosine) | Reduce adenosine dose | Theophylline/caffeine (antagonizes adenosine) | Increase adenosine dose |
| III | Amiodarone | Simvastatin, lovastatin, atorvastatin (potentiates myopathy) | Reduce statin dose or use non-CYP3A4 statins (pravastatin, rosuvastatin) | β-Blockers (summative) | Adjust dose, Monitor the ECG |
| Clopidogrel (decreases the active metabolite | Replace with prasugrel or ticagrelor | Hepatitis C antiviral drugs (potentiate bradycardia) | Monitor heart rate during the first 48 h | ||
| Dronedarone | Simvastatin, lovastatin, atorvastatin (potentiates myopathy) | Reduce statin dose or use non-CYP3A4 statins (pravastatin, rosuvastatin) | Potent CYP3A4 inhibitors (increase dronedarone) | Avoid combination | |
| Dofetilide | Cimetidine, trimethoprim, dolutegravir (reduce dofetilide OCT2 renal elimination) | Avoid combination | CYP3A4 inhibitors (+dofetilide) | Avoid combination | |
| Ibutilide/dofetilide/sotalol | Drugs producing hypokalaemia/hypomagnesaemia | Increase the risk of QT prolongation and TdP. Monitor ionic levels | Other QT-prolonging drugs | Avoid combination | |
| Vernakalant | CYP3A4 inhibitorsa (+vernakalant) | Caution | Strong CYP2D6 inhibitorsc (+vernakalant) | Caution | |
| IV | Verapamil/diltiazem | CYP3A4 substrates (+substrate) | Replace or adjust substrate dose | P-gp substrates (+substrate) | Replace or adjust substrate dose |
Supplementary material online, Table S5 gives a more comprehensive description.
+, increases levels of the AAD; −, decreases levels of the AAD; OCT2: organic cation transporter 2; AAD, anti-arrhythmic drug; CCB, calcium channel blocker; PPI, proton pump inhibitor; SSRI, selective serotonin reuptake inhibitors; TdP, torsades de pointes.
aVerapamil, grapefruit juice, azole anti-fungals, macrolides, and others (Table 14).
bPhenytoin, rifampicin and others (see Table 14).
cBupropion, SSRI (fluoxetine, fluvoxamine, paroxetine), ritonavir; others (see Table 14).