QT Prolongation Due to Roxithromycin

Postgrad Med J 2000;76:651–654 651 Postgrad Med J: first published as 10.1136/pmj.76.900.651 on 1 October 2000. Downloaded from ADVERSE DRUG REACTION QT prolongation due to roxithromycin A Woywodt, U Grommas, W Buth, W RaZenbeul Roxithromycin and other macrolide antimicro- placement of the apex beat, a prominent third bials are widely used for a broad variety of heart sound, coarse rales over both lung fields infections such as upper respiratory tract infec- and pitting oedema of both ankles. The patient tion and community acquired pneumonia. was taken to an intensive care unit. Acute myo- Prolongation of the QT interval, torsade de cardial infarction was ruled out and frusemide pointes polymorphic ventricular tachycardia, was begun intravenously. An electrocardio- and sudden death are well described but little gram (ECG) on admission showed sinus known adverse reactions common to all rhythm and incomplete left bundle branch macrolides. We report the case of a 72 year old block; QT intervals were normal (QT interval patient with congestive heart failure caused by 380 ms, corrected QT interval according to University of ischaemic heart disease who developed severe Bazett’s formula [QTc] 390 ms). Roxithromy- Hannover Medical prolongation of the QT interval after three days cin (Roussel UCLAF, Romainville, France) School, 30623 of treatment with roxithromycin. 150 mg twice a day was initiated for suspected Hannover, Germany: pneumonia. On the third hospital day, he was Department of Nephrology Case report transferred to a general medical ward. A Woywodt A 72 year old man presented with severe On admission there, the patient was gener- W Buth congestive heart failure. Three months earlier ally well with few pulmonary rales and mild he had been diagnosed with three vessel coron- pitting oedema of the ankles. An ECG showed Department of new ST depression in the left precordial leads Cardiology ary heart disease with moderately impaired left U Grommas ventricular function. Thallium scans had failed with a markedly negative T wave in V4 (fig 1). WRaZenbeul to demonstrate a distinct area of ischaemia, The most striking findings, however, were QT hence a decision had been made to refrain from and QTc intervals of 680 ms and 660 ms, Correspondence and reprint surgical treatment. Frusemide (furosemide), respectively (fig 1). Serum concentrations of requests to: Dr Alexander potassium, calcium, and both amiodarone and Woywodt, Department of digoxin, captopril, and aspirin had been begun Nephrology, University of whereas metoprolol had to be discontinued digoxin were normal. The patient denied chest Hannover Medical School, because of bradycardia. In view of the impaired pain; serum troponin T and creatine kinase Carl-Neuberg-Strasse 1, were repeatedly normal. Digoxin, roxithromy- 30623 Hannover, Germany left ventricular function, amiodarone was (email: [email protected]) started, instead of blocker, after recurrent cin, and amiodarone were discontinued and â http://pmj.bmj.com/ episodes of atrial fibrillation. On admission, the the patient taken to an intermediate care unit Submitted 16 September patient was severely dyspnoeic and appeared to permit continuous ECG monitoring. One 1999 week later he was discharged in good health Accepted 13 January 2000 acutely ill. Physical examination revealed dis- with no dyspnoea and peripheral oedema and On admission On day 3 with improved QT intervals (QT 460 ms, QTc 430 ms). V3 V3 Discussion The QT interval is often neglected during on September 29, 2021 by guest. Protected copyright. interpretation of the routine ECG. Even measurement of the QT interval is not trivial, particularly when a U wave is also present or V4 when there is gradual transition of the T wave V4 to the baseline. In general, the point at which the downslope of the T wave crosses the baseline can be used to determine the end of the QT interval,1 although an occasional ECG may still pose diYculties in this regard. Moreover, the QRS width should always be determined to V5 V5 exclude prolongation of the QT interval caused by widening of the QRS interval. The patient discussed here had a markedly 1 mV 1 mV prolonged QT interval after three days in hospital for congestive heart failure. In search of a cause for QT prolongation, inherited and 1 s 1 s acquired disorders must be considered. Irre- spective of the cause, however, markedly Heart rate 61/min Heart rate 55/min prolonged QT intervals confer a high risk of QT 380 ms QT 680 ms sudden death due to polymorphic ventricular QTc 390 ms QTc 660 ms tachycardia, particularly of the torsade de Figure 1 ECGs before and after roxithromycin treatment. pointes variant.2 Recent research has elucidated www.postgradmedj.com 652 Woywodt, Grommas, Buth, et al Postgrad Med J: first published as 10.1136/pmj.76.900.651 on 1 October 2000. Downloaded from Box 1: Drugs associated with Learning points 1–3 prolongation of the QT interval x Macrolides, as well as a broad variety of 1. Antimicrobial agents other drugs, may prolong the QT x Antimalarials (chloroquine, halofantrine, interval, cause torsade de pointes mefloquine, quinine) polymorphic ventricular tachycardia, and precipitate sudden death in susceptible x Macrolides (erythromycin, individuals roxithromycin, azithromycin, spiramycin) x If possible, macrolides should therefore be avoided in patients who already x Pentamidine receive drugs with a propensity to x Trimethoprim-sulfamethoxazole prolong the QT interval, such as 2. Drugs with predominant action on the amiodarone and histamine antagonists cardiovascular system x Class IA antiarrhythmic agents (disopyramide, quinidine, procainamide) QT prolongation. Rarely, central nervous sys- x Class IB antiarrhythmic agents tem disease or cardiac disorders such as myo- (lignocaine (lidocaine), mexiletine, cardial infarction alone account for prolonga- aprindine) tion of the QT interval. Our patient had x Class IC antiarrhythmic agents normal serum electrolytes and there were no (encainide) signs and symptoms nor laboratory evidence of ongoing cardiac ischaemia. x Class III antiarrhythmic drugs Prolongation of the QT interval has been (amiodarone, bretylium, sotalol) reported as a side eVect of numerous drugs (see x Atropine box 1).3 The patient reported here received a x Calcium antagonists (nifedipine) total of three drugs with a potential to aVect cardiac repolarisation. Before admission he Digoxin, digitoxin x had been on digoxin and amiodarone after sev- x Diuretics eral episodes of atrial fibrillation. Amiodarone x Vasodilators (prenylamine, lidoflazine, has a well documented range of side eVects, fenoxidil, bepridil) one of them being prolongation of the QT interval.3 Digoxin, too, can disturb cardiac 3. Drugs with predominant action on the 3 central nervous system repolarisation and prolong the QT interval. In hospital, roxithromycin (erythromycin 9-[O- x Amantadine [(2-methoxyethoxy)methyl] oxime]), a semi- x Antidepressants (amitriptyline, synthetic macrolide antibiotic,4 was given for doxepine), pimozide community acquired pneumonia. The propen- x Chloral hydrate sity of macrolides to prolong the QT interval is well documented5 and their ability to cause http://pmj.bmj.com/ Lithium x polymorphic tachycardia and cardiac arrest has x Phenothiazines (chlorpromazine, been described in anecdotal reports.6 Recently, thioridazine), haloperidol erythromycin was shown to block IKr, the rapid 4. Miscellaneous drugs delayed rectifier channel for potassium.7 Fac- x Corticosteroids tors that confer increased vulnerability for erythromycin induced QT prolongation are x Gastrointestinal procinetics (cisapride) still awaiting further elucidation, although x Histamine antagonists (astemizole, female sex has been proposed to be a risk on September 29, 2021 by guest. Protected copyright. terfenadine), particularly when used with factor.8 Interestingly, macrolides occasionally antifungals such as fluconazole, unmask an inherited long QT syndrome9; itraconazole, ketoconazole therefore, genetic vulnerability may also play a x Probucol part. Macrolides may also prolong the QT interval by interacting with the metabolism of Tacrolimus x other drugs that aVect cardiac repolarisation 5. Toxins such as histamine antagonists.10 x Arsenic We conclude that our patient had acquired x Organophosphates prolongation of the QT interval due to concomitant use of digoxin, amiodarone, and roxithromycin. Marked prolongation of the QT interval is associated with a high risk of genetics and molecular pathogenesis of con- polymorphic torsade de pointes ventricular genital long QT syndrome and at least six tachycardia, ventricular fibrillation and sudden forms of the disorder have been attributed to death, more so in patients with advanced myo- mutations in cardiac ion channels.1 In the cardial disease. Macrolides should therefore be patient reported here, an acquired cause of used with caution or, better still, avoided in QT prolongation was suspected since QT patients who already receive other drugs with a intervals had been normal on admission. Elec- propensity to prolong the QT interval. If mac- trolyte disturbances2 such as hypokalaemia or rolides cannot be avoided in these patients, for hypomagnesaemia, and drug eVects3 are example in chlamydial infection or legion- among the most frequent causes of acquired naire’s disease, we suggest they are used www.postgradmedj.com QT prolongation due to roxithromycin 653 Postgrad Med J: first published as 10.1136/pmj.76.900.651 on 1 October 2000. Downloaded from cautiously with close monitoring of the QT 6 Lee KL, Jim MH, Tang SC, et al. QT prolongation and torsade de pointes associated with clarithromycin. Am J Med interval. 1998;104:395–6. 7 Antzelevitch C, Sun ZQ, Zhang ZQ, et al. Cellular and ionic mechanisms underlying erythromycin-induced long QT 1 Braunwald E, ed. Heart disease. A textbook of cardiovascular intervals and torsade de pointes. 1996; : medicine. 5th Ed. Philadelphia: W B Saunders, 1996: 114 J Am Coll Cardiol 28 and 684–6. 1836–48. 2 el-Sherif N, Turitto G. The long QT syndrome and torsade 8 Drici MD, Knollmann BC, Wang WX, et al. Cardiac actions de pointes. Pacing Clin Electrophysiol 1999;22:91–110. of erythromycin. Influence of female sex.

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