Orlistat

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

Orlistat is the saturated derivative of lipstatin. Lipstatin was isolated from Streptomyces toxytricini and is also a potent inhibitor of pancreatic lipases. However, due to more simplicity and stability, orlistat rather than lipstatin was developed into an anti-obesity drug.

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 varies. In one-year clinical trials, between 35.5% and 54.8% of subjects achieved a 5% or greater decrease in body mass, although not all of this mass was necessarily fat. Between 16.4% and 24.8% achieved at least a 10% decrease in body mass. A significant number 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 gastrointestinal related. Side effects are most severe within the first year of therapy. Because orlistat's 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 faecal 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.

Despite claims that Orlistat increases the risk of breast cancer amongst clinicial trial participants, there is evidence to suggest that the introduction of specific varied preparations containing Orlistat can induce cell death in tumour cells and block their growth.

A recent animal study addressed a connection orlistat shares with aberrant crypt foci (ACF) in the colon, which is believed to be one of the earliest precursors of colon cancer.

Contraindications

Xenical is contraindicated in:

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

    • Availability

    In most areas orlistat is available by prescription only. However, in Australia it is available over-the-counter in 120mg size (84 capsules to the pack). No prescription is required unless bought by mail order, in which case a prescription is necessary. Orlistat is classified as 'Pharmacist Only Medicine' in Australia.

    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. As of October, 2006, the FDA had taken no further action.

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