Each week we will aim to bring out a concise email that provides 4-5 key pieces of information addressing a specific issue in clinical therapeutics. This week:
Drugs and QT prolongation
The QT interval reflects the measurement of the duration of ventricular depolarization and repolarization and is measured in milliseconds (ms) on an electrocardiogram (ECG) from the Q-top (the beginning of the QRS complex) to the end of the T wave. The QT interval is dependent on heart rate, gender and age. Prolongation of the QT interval can result in a life-threatening arrhythmia called Torsade de Pointes (TdP). TdP is often self-terminating but can cause ventricular fibrillation or rarely sustained ventricular tachycardia, resulting in dizziness, syncope, cardiac arrest and sometimes death. QT prolongation can be defined as more than 450ms in men and over 470ms in women.
- Many factors predispose to QT prolongation including advanced age, female gender, left ventricular hypertrophy, heart failure, myocardial ischaemia, hypertension, diabetes, and electrolyte abnormalities (including hypokalaemia and hypomagnesaemia). However, one of the most common causes of acquired QT prolongation is the use of specific drugs.
- Drug-induced QT prolongation is thought to result from blockade of cardiac potassium channels. The prolongation of the QT interval by drugs is usually seen within several days of commencing treatment. Drugs associated with QT prolongation include several antibiotics such as azithromycin, clarithromycin, erythromycin, roxithromycin and moxifloxacin, as well as antifungals including fluconazole, voriconazole and ketoconazole. Psychotropics, in particular TCAs, citalopram and escitalopram, risperidone, fluphenazine, haloperidol, clozapine, amisulpride, zisprasidone, droperidol are implicated. Antiarrhythmics such as sotalol, amiodarone and disopyramide are also important causes of iatrogenic QT prolongation. Miscellaneous agents such as cisapride, dextropropoxyphene, domperidone, methadone and solifenacin have been implicated.
- Drug interactions can significantly increase the risk of QT prolongation. Many drugs that can potentially prolong the QT interval are metabolized via the cytochrome isoenzymes CPY3A4, 1A2 and 2D6 and because most drugs that prolong the QT interval do so in a concentration-dependent manner, if metabolism is inhibited the likelihood of QT prolongation or TdP significantly increases. It is also best to avoid concomitant administration of more than one drug that prolongs the QT interval as the potential risk increases when these drugs are used in combination.
- Drugs that have the potential to prolong the QT interval should not be used at doses that exceed the recommended range, and these medications should be prescribed with particular caution for patients with underlying risk factors, such as cardiac disorders. Close monitoring of electrolytes and an ECG is recommended within the first few days of therapy in high risk patients. Further information regarding drugs that prolong the QT interval can be found at www.crediblemeds.org and www.qtdrugs.org
Please consider these issues when preparing or interpreting RMMR reports or education sessions. Contributions of content or suggested topics are welcome and should be sent directly to firstname.lastname@example.org