Sibutramine ( Meridia/Reductil ) is a serotonin and norepinephrine re-uptake inhibitor, approved for the management of obesity and overweight.

In March 2002 Sibutramine was withdrawn from the market in Italy after two deaths from cardiovascular causes and 50 other adverse events, including arrhythmias and hypertension.
The European Committee for Proprietary Medicinal Products ( CPMP ) also reassessed Sibutramine in June 2002, concluding that the risk-benefit ratio was favourable and marketing approval was subsequently re-instated.

Researchers at University of Otago, New Zealand, have presented a report of a patient who experienced a cardiac arrest shortly after starting Sibutramine and was subsequently diagnosed with congenital long QT syndrome ( LQTS ).

A 40-year-old Caucasian woman taking Sibutramine 15 mg daily for 25 days was found collapsed, unresponsive and without a detectable pulse by her husband who successfully performed cardiopulmonary resuscitation.
A 12-lead ECG revealed atrial fibrillation with a ventricular rate of 80 beats/min. The QT interval appeared prolonged.
Atrial fibrillation resolved spontaneously and subsequent ECGs detected sinus rhythm with marked QT prolongation with a heart rate corrected QT interval of 0.60 sec.
Drug-induced QT prolongation was suspected and Sibutramine was discontinued. Echocardiography, serum electrolytes and coronary angiography were normal. However, since the QT interval remained prolonged congenital LQTS was suspected.
A mutation was identified in the patient ( and subsequently her children ) in a potassium channel subunit gene, KCNQ1 ( c793t ). Mutations in this gene cause the LQTS type 1 phenotype.

Additional cases were found from analysis of the IMMP ( New Zealand Intensive Medicines Monitoring Programme ) and WHO international spontaneous reporting databases.

A further 65 IMMP reports were identified and reassessed. In this group, the most frequent events reported were those already identified in the product information. These were palpitations ( 26 cases ), dizziness/faintness ( 20 ), and tachycardia ( 10 ). Of the 26 cases of palpitations, five were associated with syncope or presyncopal symptoms and three of these patients developed symptoms within 14 days of starting Sibutramine.

In the WHO-UMC database there were 41 reports of arrhythmia, 43 reports of cardiac fibrillation ( five of these were ventricular fibrillation ), eight reports of heart block and 500 reports of tachycardia, of which four were ventricular tachycardia, 23 were supraventricular tachycardia and one was torsade de pointes. In addition, there were three reports of QT prolongation and 21 reports of cardiac arrest.
Review of the three reports of QT prolongation from the WHO database identified a 38-year-old woman diagnosed with prolonged QT 61 days after starting Sibutramine, a 48-year-old woman who developed ventricular fibrillation, but recovered 35 days after starting this drug and a 13-year-old child diagnosed with QT prolongation 1 year after starting Sibutramine. There was also one fatal case of torsade de pointes identified in a 50-year-old woman ( also taking Cisapride ) 29 days after starting Sibutramine.

The authors conclude: “ This case series suggests that Sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that Sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. “

Source: British Journal of Clinical Pharmacology, 2006


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