- 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
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.
- 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
- 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.
- 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 ), 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.
- 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.
- 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.
- 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
- Orlistat (Xenical) is approved for long-term treatment of obesity in more countries than any other weight loss pill.
- Orlistat alters nutrient absorption in the intestine by blocking pancreatic and gastric lipases; up to 30% of eaten fat is blocked.
- The U.S. FDA approved orlistat capsules, branded as Alli, as an
over-the-counter (OTC) treatment for overweight adults in February, 2007.