Know your patient’s history, drug combinations before starting a new treatment
by By Michele B. Kaufman, PharmD, BSc, RPh
Terfenadine, cisapride, astemizole … do you remember these drugs? They all were removed from the U.S. market subsequent to adverse outcomes related to QTc interval prolongation, including ventricular arrhythmias.1-3 Many drugs prolong the QTc interval, particularly if a drug is combined with others that affect its metabolism.
QTc interval prolongation can lead to torsades de pointes (TdP). Certain individuals are particularly predisposed to developing TdP, including: women, people with hypokalemia or hypomagnesemia, and those with a history of congenital or idiopathic QTc syndrome, cardiac arrest, syncope, congestive heart failure, bradycardia, baseline QT prolongation, renal failure, or cardiac failure.4 Some agents can prolong the QTc interval by five to 10 milliseconds and cause TdP, while others require a 50-millisecond increase or more.
Drugs that confer a risk of ventricular arrhythmias include: disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol, and amiodarone (antiarrhythmic agents); clarithromycin, erythromycin, levofloxacin, gatifloxacin, gemifloxacin, moxifloxacin, telithromycin (anti-infectives); domperidone and droperidol antiemetics; chlorpromazine, haloperidol, mesoridazine, thioridazine, and pimozide (antipsychotics); amitriptyline, desipramine, doxepin, fluoxetine, imipramine, sertraline, and venlafaxine (antidepressants); fluconazole, itraconazole, and ketoconazole (antifungals); naratriptan, sumatriptan, and zolmitriptan; and methadone.4-8 Other related agents, such as voriconazole and ondansetron, have been reported to cause QTc prolongation.
Drugs of special concern are those that frequently inhibit the metabolism of other agents, including erythromycin, clarithromycin, ketoconazole, itraconazole, amiodarone, and quinidine, and many antidepressants and antiretroviral agents. Of the deaths associated with drug-induced QTc prolongation related to the prokinetic agent cisapride, many were due to drug interactions with an imidazole or macrolide antibiotic. In these cases, increased serum concentrations of cisapride occurred due to inhibition of the cytochrome P450 CYP3A4 isoenzyme.9
If treatment with a drug that has the potential for causing QTc prolongation is begun, tell your patient to report any “potential cardiac” symptoms, such as palpitations, syncope, or near-syncope with or without palpitations, to a member of the healthcare team. Always be on the lookout for any concomitant conditions or treatments that can cause hypokalemia (e.g., diuretic use, gastroenteritis, diarrhea, excessive vomiting), or other agents that inhibit drug metabolism.
Obtaining a complete medication history, including the use of herbal products and over-the-counter medications, can help identify and prevent QTc prolongation from a drug interaction. A routine, 12-lead electrocardiogram (EKG) should be utilized during treatment to detect asymptomatic QTc prolongation or abnormal postectopic QTc intervals. Additionally, any patient predisposed to QTc prolongation should have an EKG performed before commencing treatment as well as after treatment is complete. If a drug prolongs the QTc interval beyond normal limits, the benefit of continuing the drug should be weighed against the risk of serious adverse cardiac events.10 TH
Michele B Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City.
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