Torsades de Pointes and QT ProlongationDue to a Combination of Loratadineand AmiodaroneSHAUL ATAR, NAHUM A. FREEDBERG, DANTE ANTONELLI,and TIBERIO ROSENFELDFrom the Department of Cardiology, Ha’Emek Medical Center, Afula, Israel

ATAR, S., ET AL.: Torsades de Pointes and QT Prolongation Due to a Combination of Loratadine andAmiodarone. Torsades de pointes (TdP) has not been previously reported with loratadine. A 73-year oldwoman on chronic treatment with amiodarone for atrial fibrillation received loratadine and presentedwith syncope and multiple episodes of TdP. We suggest that QT interval should be monitored wheneverloratadine is co-administered with drugs that may potentially prolong QT. (PACE 2003; 26:785–786)

torsades de pointes, QT interval, QT dispersion, loratadine, amiodarone

Case ReportA 73-year old hypertensive and hyperlipi-

demic patient was admitted because of a syn-copal episode. She was on chronic amiodaronetherapy (200 mg/day) for paroxysmal atrial fib-rillation, with a baseline QT interval of 400 ms,and was also taking cilazapril, pravastatin, andwarfarin. A few days prior to admission she wasgiven loratadine (10 mg/day) for a suspected aller-gic reaction. Her physical and neurological exam-ination was normal. Cardiac enzymes, liver, andrenal function tests were normal with magnesiumat 2.0 mg/mL, calcium at 9.72 mg/dL, and potas-sium at 4.05 mmol/L. Admission ECG is presentedin Figure 1A. Transthoracic echocardiography re-vealed normal systolic left ventricular function,mild left ventricular hypertrophy and significantdiastolic dysfunction. Amiodarone and loratadinewere discontinued. Rhythm monitoring revealedfrequent episodes of long-short QRS cycles pro-ceeded by torsades de pointes (TdP) (Fig. 1B) thatwere self-terminated and did not require addi-tional therapy. Over the next 4 days the QT inter-val and QT dispersion returned to normal baselineand the patient became asymptomatic.

DiscussionLoratadine and other second generation an-

tihistamines are rapidly metabolized by hepaticcytochrome P-450 enzymes (CYP 3A4) to an ac-tive metabolite that may block the rapid compo-nent of the delayed rectifier potassium channels(Ikr).1 Adverse events associated with these drugsare usually attributed to highly elevated blood

Address for reprints: Shaul Atar, M.D., Department of Cardiol-ogy, Ha’Emek Medical Center, Afula 18101, Israel. Fax: 972-4-6494387; e-mail: atar sh@clalit.org.il

Received September 13, 2002; revised October 21, 2002;accepted December 6, 2002.

levels resulting from drug overdose, significantliver dysfunction, or if given concomitantly withother drugs that inhibit cytochrome P-450 activ-ity.2 QT prolongation and TdP associated with

Figure 1. (A) Admission 12-lead ECG showing sinusbradycardia, long-short QRS cycle, multifocal ventric-ular premature beats, QT 720 ms, QTc 688 ms, and QTdispersion 160 ms. (B) Sinus bradycardia, long QT inter-val, and a long-short QRS cycle preceding one of multi-ple episodes of TdP on the patients’ rhythm monitor onthe day of admission.

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second-generation antihistamines were mainly re-ported with terfenadine and astemizol,1,2 due totheir potent blocking effect on Ikr channels. Lorata-dine and its metabolite, desloratadine, at therapeu-tic concentrations and even at high doses, blockIkr channels with a much lesser potency.3 Lorata-dine does not significantly prolong QT intervaland is considered clinically safe.1,2,4 The drug hasnot been previously associated with syncope andTdP, and currently no specific caution is requiredwith respect to its administration in hepatic fail-ure and no racial or sex variations in the dispo-sition have been noted.4 Even when administeredin combination with cytochrome P-450 inhibitorsor at several times the recommended dose, anddespite sustained elevations of plasma concen-trations, no clinically relevant drug accumulationwas reported.4

Amiodarone is metabolized by the liver, andinteracts with the clearance of many drugs. Apartial explanation of these interactions may in-

volve the formation of an inactive cytochromeP-450Fe(II)-metabolite complex.5 QT prolongationmay occur with amiodarone treatment.6 However,TdP associated with amiodarone is uncommon,the reasons for which are not fully elucidated.7,8

Possible explanation may be attributed to the ef-fect of amiodarone on sodium and calcium chan-nels that participate in production of early after-depolarizations and TdP. Amiodarone was alsoshown to decrease QT dispersion and thus preventTdP.9

In our patient no immediate precipitating fac-tor for TdP was found other than the additionof loratadine to chronic amiodarone treatment.We suggest that prior to prescribing loratadineconcomitantly with drugs that may potentiallyprolong QT, an ECG should be done and repeatedseveral hours after ingestion of the first dose. Oncean increase in QT interval or dispersion is noted,loratadine should be discontinued and rhythmmonitoring initiated.

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tamines. Curr Med Chem 1997; 4:171–184.2. Honig PK, Wortham DC, Zamani K, et al. Terfenadine-ketoconazole

interaction. Pharmacokinetic and electrocardiographic conse-quences. JAMA 1993; 269:1513–1518.

3. Taglialatela M, Castaldo P, Pannaccione A, et al. Cardiac ion chan-nels and antihistamines: Possible mechanisms of cardiotoxicity. ClinExp Allergy 1999; 29(suppl 3):182–189.

4. Henz BM. The pharmacologic profile of desloratadine: A review.Allergy 2001; 56(suppl):7–13.

5. Larrey D, Tinel M, Letteron P, et al. Formation of an inactivecytochrome P-40Fe(II)-metabolite complex after administration ofamiodarone in rats, mice and hamsters. Biochem Pharmacol 1986;35:2213–2220.

6. Debbas NMG, du Cailar C, Bexton RS, et al. The QT interval: A pre-dictor of the plasma and myocardial concentrations of amiodarone.Br Heart J 1984; 51:316–320.

7. Lazzara R. Antiarrhythmic drugs and TdP. Eur Heart J 1993; 14(supplH):88–92.

8. Hii JTY, Wyse DJ, Gillis AM, et al. Precordial QT interval dis-persion as a marker of TdP. Disparate effects of class IA an-tiarrhythmic drugs and amiodarone. Circulation 1992; 86:1376–1382.

9. Verduyn SC, Vos MA, LeunissenHD, et al. Evaluation of theacute electrophysiologic effects of intravenous dronedarone, anamiodarone-like agent, with special emphasis on ventricular repo-larization and acquired torsade de pointes arrhythmias. J CardiovascPharmacol 1999; 33:212–222.

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