The consensus of opinion is that the concurrent use of two or more drugs that prolong
the QT interval should generally be avoided because of the risk of additive effects,
leading to the possible development of serious and potentially life-threatening torsade
de pointes arrhythmias. It is thought that torsade de pointes is unlikely to develop
until the corrected QT (QTc) interval exceeds 500 milliseconds, but this is not an exact
figure and the risks are uncertain and unpredictable. Because of these uncertainties,
many drug manufacturers and regulatory agencies now contraindicate the concurrent
use of drugs known to prolong the QT interval, and a 'blanket' warning is often issued
because the QT-prolonging effects of the drugs are expected to be additive. The extent
of the drug-induced prolongation usually depends on the dosage of the drug and the
particular drugs in question. For some drugs QT prolongation is a fairly frequent effect
when the drug is used alone, and it is well accepted that use of these drugs requires
careful monitoring (e.g. a number of the antiarrhythmics). Pairs of antiarrhythmics
should therefore be avoided where possible. For other drugs, QT prolongation is rare,
but because of the relatively benign indications for these drugs, the risk-benefit ratio is
considered poor, and use of these drugs has been severely restricted or discontinued
(e.g. astemizole, terfenadine, cisapride). For others there is less clear evidence of the
risk of QT prolongation (e.g.
tacrolimus, tamoxifen, tricyclic antidepressants) and
therefore the associated risks of combinations of these types of drug are much lower.
Drugs known to have a high risk of causing QT-prolongation include:
Antiarrhythmics (class Ia: disopyramide, procainamide, quinidine)
Antiarrhythmics (class III: amiodarone, sotalol)
Antihistamines (astemizole, terfenadine, if levels raised, and possibly mizolastine)
Antimalarials (artemether, present in co-artemether, and other artemisinin deriva-
tives, halofantrine)
Antipsychotics (amisulpride, droperidol, haloperidol (high dose and intravenous
use), pimozide, sertindole, thioridazine)
Arsenic trioxide
Erythromycin (intravenous, but see also, below)
Ranolazine
Sparfloxacin (see also, below)
Drugs known to be associated with some risk of causing QT-prolongation include:
Clomipramine (risk with other tricyclics appears to be mainly in overdose)
Chlorpromazine
Lithium (if levels raised)
Macrolides (clarithromycin, oral erythromycin, (see also, above), spiramycin)
Methadone (doses greater than 100 mg)
Quinolones (gatifloxacin, levofloxacin, moxifloxacin, and see also, above)
Pentamidine intravenous
Quinine
Further, hypokalaemia increases the risks of torsade de pointes arrhythmias and so
potassium levels should be closely monitored when drugs that can cause hypokalae-
mia are used with drugs that prolong the QT interval. However, there appear to be very
few reports of this interaction.Drugs known to lower potassium levels include:
Amphotericin B
Corticosteroids
Loop diuretics
Salbutamol (Albuterol) and related bronchodilators
Stimulant laxatives
Theophylline
Thiazide diuretics