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Sibutramine-Associated QT Interval Prolongation and Cardiac Arrest

Director of Intensive Care, Box Hill Hospital, Victoria, Australia

Alexander Gershenzon, MBBS

Intensive Care Registrar, Box Hill Hospital

Carmela E Corallo, BPharm Grad Dip Hosp Pharm

Deputy Director of Pharmacy, Box Hill Hospital

Ramesh Nagappan, MBBS MD FRACP FJFICM

Intensive Care Specialist, Box Hill Hospital

Reprints: Prof. Ernest, Box Hill Hospital, Nelson Rd., Box Hill, Victoria 3128, Australia, fax 61 3 98954808, david.ernest{at}easternhealth.org.au

OBJECTIVE: To report on a probable association between sibutramine and QT interval prolongation leading to ventricular fibrillation and cardiac arrest.

CASE SUMMARY: A previously well 51-year-old woman with obesity but no other relevant past medical history or cardiac risk factors was prescribed sibutramine (initial dose 10 mg daily, increased to 15 mg daily after 10 wk). Four months after initiation of therapy, the woman developed ventricular fibrillation and was successfully resuscitated. On admission, an electrocardiogram (ECG) demonstrated sinus tachycardia without any ischemic changes and a prolonged QTc interval (545 msec). A subsequent coronary angiogram revealed normal coronary arteries and no other abnormalities. Her QTc interval returned to normal (432 msec) by day 2 and remained within normal limits (<440 msec) thereafter. Due to a favorable neurologic recovery and the absence of any cardiac structural abnormality, the patient was readmitted for implantation of an automatic implantable cardioverter-defibrillator on day 35 and remained well from a cardiac and neurologic standpoint at a 2-year follow-up examination.

DISCUSSION: Sibutramine acts centrally to inhibit noradrenaline, dopamine, and serotonin reuptake, thereby sharing similar actions of other QT interval–prolonging drugs. Therefore, sibutramine might be anticipated to also share a tendency to QT interval prolongation. The current prescribing information for sibutramine does not specifically list any precautions or adverse reactions related to QT interval prolongation. QT interval prolongation associated with sibutramine in this case is considered probable based on the Naranjo probability scale.

CONCLUSIONS: Clinicians prescribing sibutramine should monitor their patients for ECG abnormalities and be cautious in coprescribing drugs known to prolong the QT interval.

Key Words: cardiac arrest, QT interval, sibutramine, ventricular fibrillation

Published Online, August 26, 2008. www.theannals.com, DOI 10.1345/aph.1L129