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Orlistat

Orlistat (marketed as Xenical by Roche) is a drug designed to treat obesity. Its primary function is to prevent the absorption of dietary fats, thereby reducing caloric intake. It is intended for use in conjunction with a physician-supervised reduced calorie diet. more...

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Pharmacology

Orlistat works by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. Without this enzyme, triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested. Only trace amounts of orlistat are absorbed systemically, the primary effect is local lipase inhibition within the GI tract after an oral dose. The primary route of elimination is through the feces.

At the standard prescription dose of 120 mg three times daily before meals, orlistat prevents approximately 30% of dietary fat from being absorbed.

Efficacy

The amount of weight loss achieved with orlistat is variable. In 1 year clinical trials, between 35.5% and 54.8% of subjects achieved a 5% or greater decrease in body mass. Between 16.4% and 24.8% achieved at least a 10% decrease in body mass. A significant amount of subjects regained the weight after they stopped using orlistat. Despite this cosmetically small effect, there was a 37% reduction in the incidence of Type 2 diabetes, a significant difference.

Side effects

The primary side effects of the drug are GI-related. Side effects were most severe within the first year of therapy. Because its main effect is to prevent dietary fat from being absorbed, the fat is excreted unchanged in the feces and so the stool may become oily or loose. Increased flatulence is also common. Bowel movements may become frequent or urgent. Rare occurrence of fecal incontinence have been seen in clinical trials. To minimize these effects, foods with high fat content should be avoided.

The absorption of fat-soluble vitamins are inhibited by the use of orlistat. A multivitamin tablet containing these vitamins (D, E, A and beta-carotene) should be taken once a day, at least 2 hours before or after taking the drug.

Contraindications

Xenical is contraindicated in:

  • Malabsorption
  • Reduced gallbladder function (e.g. after cholecystectomy)
  • Pregnancy and breastfeeding
  • Certain kidney problems

Availability

In most areas orlistat is available by prescription only. In 2004, a lower-dose version of the drug (60 mg compared to 120 mg for the prescription version) was released over the counter in Australia and New Zealand; the United States is expected to follow in the near future.

On January 23, 2006, a US Food and Drug Administration advisory panel voted 11 to 3 to recommend the approval of an OTC formulation of orlistat (planned to be marketed under the name "Alli" by GlaxoSmithKline). The proposed product will consist of 60 mg dosage units, similar to the OTC products available elsewhere.

Read more at Wikipedia.org


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