Xenical (Orlistat)

• Generic name: Orlistat (tetrahydrolipstatin)
• Trade names: Xenical, Alli
• Dosages: Capsules 120 mg; 60 mg.
• Pharmacologic category: Lipase Inhibitor
• FDA approved: April 23, 1999
• Pregnancy risk factor: B

Medical uses

Xenical (Orlistat) is an anti-obesity medication used together with a reduced-calorie diet to treat obesity in people with certain risk factors (such as diabetes, high blood pressure, and high cholesterol or triglycerides).

Orlistat promotes loss of weight by preventing the digestion and absorption of dietary fat. So orlistat will have little effect in people eating a low-fat diet.

Side effects of Xenical are largely gastrointestinal in nature and related to the pharmacologic effect of orlistat on preventing the absorption of ingested fat. Most common side effects include: bowel movement urgency; gas with discharge; inability to control bowel movements; increased number of bowel movements; oily discharge; oily or fatty stools; oily spotting.

Pharmacological characteristics

• Elimination half-life: half-life for M1 metabolite is approximately 3 h; half-life M3 metabolite is approximately 13.5 h; half-life of absorbed orlistat is 1 to 2 h.
• Metabolism: Occurs mainly in the gastrointestinal wall. Two metabolites are M1 (4-member lactone ring hydrolyzed) and M3 (M1 with N-formyl leucine moiety cleaved); considered pharmacologically inconsequential.
• Excretion: Eliminated by fecal excretion (major route); biliary excretion for metabolites. 97% eliminated through feces, 83% as unchanged drug, and less than 2% through urine.

Benefits

• Effective weight loss. About 81% of users are satisfied or very satisfied with Xenical. It is effective in weight loss, weight maintenance and prevention of weight regain. Provides rapid and continuous weight loss in the first 12 weeks of treatment.
• Beneficial effects on blood pressure. Xenical therapy promotes reduction in blood pressure (mean reductions of 2.5 and 1.9 mmHg in systolic and diastolic blood pressure respectively [3]), cholesterol and blood sugar.
• Anti-diabetic properties. Xenical is the first weight loss medication to show a reduction in the risk of developing type 2 diabetes1. It also helps to improve glycemic control in individuals with type 2 diabetes.
• Acts only in the digestive system. Does not affect other body systems, and unlike appetite suppressants does not act on the brain. The systemic exposure to orlistat is minimal.
• Low potential for misuse. Not centrally acting.
• Low potential for drug interactions.

Concerns

• Can lead to vitamin deficiency. By blocking fat absorption, Xenical also make it harder for your body to absorb fat-soluble vitamins A, D, E and K, as well as beta-carotene.
• Increased risk of kidney stone formation. Fat malabsorption induced by the orlistat elevates the risk of developing kidney stones, especially with a high intake of oxalate-containing foods.
• High rate of gastrointestinal side effects such as oily spotting or discharge, gas with discharge, fatty or oily stools, increased bowel movements, an urgent need to have them and an inability to control them. These bowel difficulties are caused by the excretion of undigested fat and typically occur after high-fat meals.
• Possible drug interactions with cyclosporine, warfarin, amiodarone, and thyroxine4.
• High cost.

Unlabeled uses

• Polycystic ovarian syndrome (PCOS)2

Mechanism of action

Orlistat is a lipase inhibitor. It works by preventing the absorption of dietary fat in stomach.

Enzymes in the digestive system, called lipases, help digest (or break down) fat. When taken with meals, Xenical (Orlistat) attaches to the lipases and blocks them from breaking down some of the fat you have eaten. The undigested fat cannot be absorbed and is eliminated in the bowel movements. By working this way, Orlistat helps block about one-third of the fat in the foods you eat from being absorbed by the body.

References

• 1. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese persons. Diabetes Care. 2004 Jan;27(1):155-61.
• 2. Diamanti-Kandarakis E, Katsikis I, Piperi C, Alexandraki K, Panidis D. Effect of long-term orlistat treatment on serum levels of advanced glycation end-products in women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2007 Jan;66(1):103-9.
• 3. Siebenhofer A, Horvath K, Jeitler K, Berghold A, Stich AK, Matyas E, Pignitter N, Siering U. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007654.
• 4. Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS. Orlistat-associated adverse effects and drug interactions: a critical review. Drug Saf. 2008;31(1):53-65. PubMed

By HealthyStock Research Group, October 2009
Medical resources reviewed: August 2018