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sibutramine (Meridia, Reductil)

Withdrawn from US market 10/08/2010 [11] Indications: - weight loss (43% long-term weight loss [2]) large weight loss maintained for 1 year [8] - obesity Contraindications: - history of coronary artery disease - history of stroke or transient ischemic attack - history of cardiac arrhythmias - history of congestive heart failure - history of peripheral arterial disease - uncontrolled hypertension (e.g., > 145/90 mmHg) [10] Dosage: 1) start 10 mg PO QD 2) may increase to 15 mg PO QD after 4 weeks 3) max 15 mg QD 5) intermittent therapy (4 month on, 2 months off) may be as effective as continuous therapy [5] Tabs: 10 mg, 15 mg. Pharmacokinetics: -> metabolized in the liver by cyt P450 3A4 Adverse effects: 1) hypertension 2) tachycardia 3) increased risk for cardiovascular events among adults with cardiovascular disease [11] a) myocardial infarction (4.1% vs 3.2%) [6,11] b) stroke (2.6% vs 1.9%) [6,11] 5) SIADH & hyponatremia [7] 6) low discontinuation rate [8] Drug interactions: 1) other serotonergic agents (may lead to serotonin syndrome) 2) alcohol 3) cimetidine 4) any drug that inhibits cyt P450 3A4 may increase levels of sibutramine 5) any drug that induces cyt P450 3A4 may diminish levels of sibutramine Laboratory: - sibutramine in blood - sibutramine in serum/plasma - sibutramine in urine Mechanism of action: 1) appetite suppressant 2) serotonin & norepinephrine re-uptake inhibitor Weight loss of: a) 7.8 kg vs 3.8 kg over 1 year in obese patients with body mass index of 30-40 (22-25 normal) [5] b) better than placebo [9]

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) serotonin syndrome (serotonism) weight loss

General

selective serotonin reuptake inhibitor (SSRI)

Properties

MISC-INFO: elimination route LIVER

Database Correlations

PUBCHEM correlations

References

  1. Kaiser Permanente Pharmacy update
  2. Journal Watch 21(5):38, 2001 James WP et al Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 356:2119, 2000 PMID: 11191537
  3. Drug Bulletin, Kaiser Permanente, 27:2, 2001
  4. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  5. Journal Watch 21(21):173, 2001 Wirth A & Krause J Long-term weight loss with sibutramine: a randomized controlled trial. JAMA 286:1331, 2001 PMID: 11560538
  6. Prescriber's Letter 9(4):23 2002 FDA MedWatch - Meridia (sibutramine): Early Communication about cardiovascular events http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm191655.htm
  7. Prescriber's Letter 9(8):38 2002
  8. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK, Hesson LA, Osei SY, Kaplan R, Stunkard AJ. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med. 2005 Nov 17;353(20):2111-20. PMID: 16291981
  9. Berkowitz RI et al Effects of sibutramine treatment in obese adolescents. A randomized trial. Ann Intern Med 2006, 145:81 PMID: 16847290 - Dietz WH What constitutes successful weight management in adolescents? Ann Intern Med 2006, 145:145 PMID: 16847296
  10. FDA MedWatch Meridia (sibutramine hydrochloride): Follow-Up to an Early Communication about an Ongoing Safety Review http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm198221.htm11) James WP, - James WP et al Effect of Sibutramine on Cardiovascular Outcomes in Overweight and Obese Subjects N Engl J Med 2010; 363:905-917 PMID: 20818901 http://www.nejm.org/doi/full/10.1056/NEJMoa1003114
  11. FDA MedWatch 10/08/2010 Meridia (sibutramine): Market Withdrawal Due to Risk of Serious Cardiovascular Events http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm