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orlistat (Xenical, Alli)

Tradenames: Xenical, Alli (OTC). C29H53NO5. Indications: 1) weight reduction (> 30 lbs overweight) 2) overweight patients with diabetes mellitus type 2 - for use in combination with metformin 3) weight reduction in obese adolescents * no long-term effectiveness [14] Contraindications: malabsorption syndrome Dosage: 1) 120 mg with meals 2) in combination with American Heart Association diet 3) psyllium (Metamucil) 6 g (1 round tsp) with each dose of orlistat can reduce GI symptoms [3] 4) take in combination with multivitamin [6] Xenical 120 mg. Alli 60 mg (OTC) [6] Pharmacokinetics: not systemically absorbed Adverse effects: (generally diminish with time) 1) lower gastrointestinal distress a) oily spotting (4-25%) b) flatus with discharge (2-21%) c) fecal urgency (1-15%) d) fatty/oily stools (5-17%), steatorrhea e) increased defecation (2-6%) f) fecal incontinence (2-9%) [5] g) diarrhea [14] 2) reports of serious liver injury, including 6 cases of liver failure [9] - probably not hepatotoxic [11] 3) urinary calculi (hyperoxaluria, calcium oxalate stones) [10,13] 4) malnutrition [14] - diminishes absorption of fat-soluble vitamins Drug interactions: - not recommended with cyclosporine Mechanism of action: 1) reversible inhibitor of lipase within the GI tract 2) forms covalent bond with active serine residues of gastric & pancreatic lipases 3) inhibits dietary fat absorption by about 30% 4) systemic absorption is minimal 5) diminishes absorption of fat Notes: Alli (OTC) about $2/day (2007) [7]

General

amide enzyme inhibitor ester metabolic agent (metabolic modifier)

Properties

INHIBITS: bile salt-activated lipase SIZE: MW = 496 GRAMS/MOLE

Database Correlations

PUBCHEM correlations

References

  1. Roche product information
  2. Kaiser Permanente Northern California Regional Drug Formulary, Update 9/99
  3. Prescriber's Letter 8(9):50, 2001
  4. Journal Watch 22(17):132, 2002 Miles JM et al, Diabetes Care 25:1123, 2002
  5. Journal Watch 25(14):111, 2005 Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA. 2005 Jun 15;293(23):2873-83. PMID: 15956632 - Joffe A. Pharmacotherapy for adolescent obesity: a weighty issue. JAMA. 2005 Jun 15;293(23):2932-4. No abstract available. PMID: 15956639
  6. Prescriber's Letter 13(3): 2006 Acomplia (Rimonabant) and OTC Orlistat for Weight Loss Detail-Document#: 220313 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 14(3): 2007 FDA Approves Orlistat for Over-the-Counter Use Detail-Document#: 230310 (subscription needed) http://www.prescribersletter.com
  8. Prescriber's Letter 14(7): 2007 OTC Orlistat (Alli) for Weight Loss: An Update Detail-Document#: 230702 (subscription needed) http://www.prescribersletter.com
  9. FDA MedWatch http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm180025.htm http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213448.htm
  10. Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
  11. Douglas IJ et al. Orlistat and the risk of acute liver injury: Self controlled case series study in UK Clinical Practice Research Datalink. BMJ 2013 Apr 12; 346:f1936. PMID: 23585064
  12. Hong J-L et al. Risk of colorectal cancer after initiation of orlistat: Matched cohort study. BMJ 2013 Aug 27; 347:f5039. PMID: 23982291 http://www.bmj.com/content/347/bmj.f5039
  13. Weir MA, Beyea MM, Gomes T et al Orlistat and acute kidney injury: an analysis of 953 patients. Arch Intern Med. 2011 Apr 11;171(7):703-4. PMID: 21482850
  14. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/