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Contraindicated Use of Sibutramine and Cardiovascular Adverse Reactions

OTTAWA, CANADA -- October 15, 2007 -- Sibutramine (Meridia), a serotonin and norepinephrine reuptake inhibitor, is an antiobesity agent marketed in Canada since February 2001. Sibutramine is indicated as adjunctive therapy within a weight management program for obese patients with an initial body mass index (BMI) of 30 kg/m² or higher, and for obese patients with an initial BMI of 27 kg/m² or higher in the presence of other risk factors (e.g., controlled hypertension, type 2 diabetes, dyslipidemia, visceral fat).(1)

Health Canada continues to receive reports of ARs in patients using sibutramine who have contraindications. From Jan. 1, 2001, to May 31, 2007, Health Canada received 65 reports of cardiovascular ARs suspected of being associated with sibutramine. Thirteen of these reports involved patients with at least 1 contraindicated condition. A brief description of these 13 cases follows.

The Canadian product monograph of sibutramine includes several contraindications. Noncompliance with contraindications could result in serious adverse reactions (ARs).*

Contraindications for sibutramine therapy include: (1)

· History of coronary artery disease, congestive heart failure, arrhythmias or cerebrovascular disease (stroke or transient ischemic attack)
· Inadequately controlled (> 145/90 mm Hg) or unstable hypertension
· Psychiatric illness
· Concomitant use of centrally acting drugs (e.g., antidepressants and antipsychotics) or herbal remedies (eg, St John's Wort) for the treatment of psychiatric disorders; monoamine oxidase inhibitors; or other centrally acting weight-reducing agents
· History of, or presence of, a major eating disorder such as anorexia nervosa or bulimia nervosa
· Hypersensitivity to sibutramine or to any ingredient in the formulation or component of the container

A patient with a history of myocardial infarction (MI) who was taking fluoxetine experienced fatal ventricular fibrillation 2 days after starting sibutramine therapy.

A patient with a history of MI experienced a non ST-segment elevation MI 21 days after starting sibutramine therapy.

Three patients experienced serotonin syndrome, with cardiovascular ARs (e.g., hypertension, palpitation and tachycardia), from the concomitant use of a selective serotonin reuptake inhibitor (SSRI) and sibutramine.

Five patients with a previous history of arrhythmia had arrhythmia while taking sibutramine.

One patient took 10 capsules in 3 days and experienced tachycardia and confusion during concomitant use of sibutramine with other weight-reducing agents not currently authorized for sale in Canada.

One patient, who experienced unstable hypertension after surgery, resumed her preoperative regimen of sibutramine 2 days after surgery and experienced worsening hypertension, headache and cerebral oedema. In this case, meperidine was reported as a co-suspect drug.

One patient experienced a vitreous hemorrhage approximately 10 days after starting sibutramine therapy. In this case, paroxetine and bupropion were stopped 1 day before sibutramine was started.

Sibutramine used at therapeutic doses has been reported to substantially increase blood pressure and heart rate in some patients.(1, 2) Such increases were observed within the first 4 months of therapy.(1) Regular monitoring of blood pressure and heart rate is required when prescribing sibutramine.(1) In the first 3 months of treatment, these parameters should be checked at least every 2 weeks and regularly every 1-3 months thereafter.(1)

In 2002 and 2003, international regulatory actions were taken, including safety notices, concerning cardiovascular ARs associated with sibutramine.(2, 3, 4) Health Canada and other foreign regulatory agencies reviewed the safety of sibutramine and concluded that the benefit-risk profile of sibutramine remained favourable.4 Contraindications to the use of sibutramine are well detailed in the Canadian product monograph. Health Canada continues to monitor ARs suspected of being associated with sibutramine.

Before starting treatment with sibutramine, health professionals are encouraged to review its labelled contraindications in the product monograph. Consumers are encouraged to consult the consumer information leaflet provided in the original packaging, particularly the section "When it should not be used".


* A serious adverse reaction is one that requires in-patient hospitalization or prolongation of existing hospitalization, causes congenital malformation, results in persistent or significant disability or incapacity, is life-threatening or results in death. Adverse reactions that require significant medical intervention to prevent one of these outcomes are also considered to be serious.


REFERENCES:
1. Meridia (sibutramine hydrochloride monohydrate) [product monograph]. Saint-Laurent (QC): Abbott Laboratories Ltd; 2005.
2. Nisoli E, Carruba MO. A benefit-risk assessment of sibutramine in the management of obesity. Drug Saf 2003;26(14):1027-48. [ PubMed]
3. Health Canada investigates safety of Meridia (sibutramine). Ottawa: Health Canada; 2002 Mar 27. Available: www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2002/2002_21_e.html (accessed 2007 July 10).
4. Health Canada reports back to public on safety profile of Meridia (sibutramine). Ottawa: Health Canada; 2003 Feb 28. Available: www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2003/2003_07_e.html (accessed 2007 July 10).


SOURCE: Health Canada

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