This section is mainly concerned with class I antiarrhythmics, which also possess some local anaesthetic properties, and with class III antiarrhythmics. Antiarrhythmics that fall into other classes are dealt with under beta blockers,, digitalis glycosides, , and calcium-channel blockers, . Some antiarrhythmics that do not fit into Vaughan Williams classification (see table 1 below,(below)) are also included in this section (e.g. adenosine). Interactions in which antiarrhythmic drug is affecting substance, rather than drug whose activity is altered, are dealt with elsewhere.
It is difficult to know exactly what is likely to happen if two antiarrhythmics are used together. The hope is always that a combination will work better than just one drug, and many drug trials have confirmed that hope, but sometimes combinations are unsafe. Predicting unsafe combinations is difficult, but there are some very broad general rules that can be applied if general pharmacology of drugs is understood.
If drugs with similar effects are used together, whether they act on myocardium itself or on conducting tissues, total effect is likely to be increased (additive). The classification of antiarrhythmics in table 1 below, (see below) helps to predict what is likely to happen, but remember that classification is not rigid so drugs in one class can share some characteristics with others. The following sections deal with some examples.
(a) Combinations of antiarrhythmics from same class
The drugs in class Ia can prolong QT interval so combining drugs from this class would be expected to show an increased effect on QT interval. This prolongation carries risk of causing torsade de pointes arrhythmias (see monograph, Drugs that prolong QT interval + Other drugs that prolong QT interval interaction). It would also be expected that negative inotropic effects of quinidine would be additive with procainamide or any of other drugs within class Ia. For safety therefore it is sometimes considered best to avoid drugs that fall into same subclass or only to use them together with caution.
Class III antiarrhythmics such as amiodarone can also prolong QT interval, so they would also be expected to interact with drugs in other classes that do same, namely class Ia drugs (see Drugs that prolong QT interval + Other drugs that prolong QT interval interaction). Verapamil comes into class IV and has negative inotropic effects, so it can interact with other drugs with similar effects, such as beta blockers, which fall into class III. For safety you should always look at whole drug profile and take care with any two drugs, from any class, that share a common pharmacological action.
Class I: Membrane stabilising drugs (a) Ajmaline, Cibenzoline (Cifenline),* Disopyramide, Procainamide, Quinidine (b) Aprindine, Lidocaine, Mexiletine, Tocainide (c) Flecainide, Propafenone Class I, but not easily fitting above subgroups – Moracizine
Class II: Beta blocker activity Atenolol,Bretylium,† Propranolol
Class III: Inhibitors of depolarisation Amiodarone,Azimilide, Bretylium,† Cibenzoline (Cifenline),* Dofetilide, Dronedarone, Ibutilide, Sotalol
Class IV: Calcium-channel blocker activity Cibenzoline (Cifenline),* Diltiazem,Verapamil
(See reference number *)Cibenzoline has class Ia,and also some class III and IV activity
| Table 1 Antiarrhythmics (modified Vaughan Williams classification) |
|---|
| Class I: Membrane stabilising drugs (a) Ajmaline, Cibenzoline (Cifenline),* Disopyramide, Procainamide, Quinidine (b) Aprindine, Lidocaine, Mexiletine, Tocainide (c) Flecainide, Propafenone Class I, but not easily fitting the above subgroups – Moracizine |
| Class II: Beta blocker activity Atenolol, Bretylium,† Propranolol |
| Class III: Inhibitors of depolarisation Amiodarone, Azimilide, Bretylium,† Cibenzoline (Cifenline),* Dofetilide, Dronedarone, Ibutilide, Sotalol |
| Class IV: Calcium-channel blocker activity Cibenzoline (Cifenline),* Diltiazem, Verapamil |
| Drugs not fitting into this classification Adenosine |
| Table 2 Antiarrhythmics (modified Vaughan Williams classification) |
|---|
| Class I: Membrane stabilising drugs (a) Ajmaline, Cibenzoline (Cifenline),* Disopyramide, Procainamide, Quinidine (b) Aprindine, Lidocaine, Mexiletine, Tocainide (c) Flecainide, Propafenone Class I, but not easily fitting the above subgroups – Moracizine |
| Class II: Beta blocker activity Atenolol, Bretylium,† Propranolol |
| Class III: Inhibitors of depolarisation Amiodarone, Azimilide, Bretylium,† Cibenzoline (Cifenline),* Dofetilide, Dronedarone, Ibutilide, Sotalol |
| Class IV: Calcium-channel blocker activity Cibenzoline (Cifenline),* Diltiazem, Verapamil |
| Drugs not fitting into this classification Adenosine |