Orlistat, also known as tetrahydrolipstatin, is a drug designed to treat obesity. It works primarily by reducing the amount of fat that is absorbed by the diet. Obese people who meet specific height and weight requirements are prescribed orlistat to lose weight and maintain the healthier weight. The drug's most common side effects are gastrointestinal.
It was approved by the Food and Drug Administration in April 1999.
Orlistat is marketed in the U.S. by Roche under the brand name Xenical (a prescription drug), and by GlaxoSmithKline under the brand name Alli (an over-the-counter drug).
Orlistat is used for weight loss and maintenance of a healthy weight. It is used in obese patients who have a body mass index (BMI) of ≥ 30 kg/m2, or a BMI of ≥ 27 kg/m2 in the presence of other risky conditions such as high blood pressure, diabetes, or high cholesterol. Body mass index is calculated based on height and weight.
How Orlistat is Taken
Orlistat is marketed as either Xenical or Alli. Xenical is available in capsules of 120 mg, whereas Alli, the over-the-counter form of orlistat, is available at a dose of 60 mg. Regardless of the dose, one capsule is taken three times a day either with a meal or within one hour of a meal containing fat. The capsule is not taken if a meal is skipped, or if it does not contain fat. For the pill to be maximally effective, meals eaten during treatment should contain 30% of calories from fat, and the day's consumption of fat should be spread over three meals. Orlistat is used in combination with a low-calorie diet and supplements of fat-soluble vitamins.
How Orlistat Works
Enzymes made in the pancreas and stomach break down the fat consumed in a meal, which facilitates absorption. Orlistat inhibits these enzymes in the intestines and prevents fat breakdown, which in turns prevents absorption of up to 30% of the fat in a meal. The undigested fat passes through the body and is eliminated in bowel movements. Orlistat only works while it is being taken; patients may regain lost weight if the drug is discontinued.
How the body affects orlistat
Very little orlistat is absorbed into the body from the intestines. The wall of the stomach metabolizes, or modifies, orlistat to a minor extent. The amount of time needed to reduce the concentration of orlistat in the body by half, the half-life, is one to two hours. Most of the drug is eliminated from the body in the feces.
Some of orlistat's more common side effects result from the fact that unabsorbed fat, rather than being broken down, passes straight through the body unchanged. They include the following:
- Oily spotting of the underwear
- Gas with discharge
- Urgent need to have a bowel movement
- Oily or fatty stools (steatorrhea)
- Oily discharge
- Increased number of bowel movements
- Inability to control bowel movements
- Abdominal pain
These side effects are generally mild to moderate in intensity. They may worsen if the drug is taken with a diet containing more than 30% of calories from fat.
Less frequent side effects include kidney and liver damage.
In clinical trials, orlistat was shown to promote weight loss, and lower the risk of diabetes.
An analysis of the effectiveness of long-term orlistat use was performed in 16 clinical trials; the total number of participants was 10,631. On average, orlistat reduced weight by 2.9 kg (6 lbs) compared to treatment with a placebo. Orlistat also reduced the incidence of diabetes. In patients with diabetes, orlistat lowered concentrations of total cholesterol, low-density lipoprotein (the “bad” cholesterol), and blood pressure while improving the control of blood sugar levels. It also slightly reduced concentrations of high-density lipoproteins, or the “good” cholesterol.
Orlistat is normally not used in patients with the following conditions:
- Problems absorbing food
- Gallbladder problems
- Pregnancy or breast-feeding
Orlistat prevents the absorption of fat-soluble vitamins such as vitamins A, D, E, and K. It also prevents the absorption of beta carotene. Multivitamin supplements should be taken to replenish vitamin stores. Supplements work best when taken at least two hours before or after taking orlistat.
Studies in healthy volunteers have shown that orlistat can hinder the absorption of a few drugs. The combination of cyclosporine (Neoral) with orlistat reduced blood concentrations of cyclosporine by approximately 30%. Taking cyclosporine two or more hours before or after orlistat helps reduce the risk of an interaction, but monitoring of patients receiving both drugs is often performed. Co-administration of orlistat with amiodarone (Cordarone) reduced the absorption of amiodarone by 25%.
Orlistat can also influence the effectiveness of some drugs. Co-administration of the anticoagulant (blood thinner) warfarin with orlistat did not affect the blood concentrations or action of warfarin in a study of healthy volunteers. However, a report of an interaction between warfarin and orlistat has been reported. In this report, a man taking both warfarin and orlistat had an increased effect of the warfarin so that his blood became thinner than intended. Orlistat may have interfered with the absorption of vitamin K, which normally inhibits warfarin. Close monitoring of patients taking both warfarin and orlistat has been advised.
Orlistat has received some unfavorable press coverage owing to its messy side effects. Its practical effectiveness, too, has been questioned, with one obesity expert calling it "a failed prescription drug from a marketing perspective."
- ↑ Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007 Dec 8;335(7631):1194-9. Abstract | PDF
- ↑ Zhi J, Moore R, Kanitra L, Mulligan TE. Pharmacokinetic evaluation of the possible interaction between selected concomitant medications and orlistat at steady state in healthy subjects. J Clin Pharmacol. 2002 Sep;42(9):1011-9. Abstract
- ↑ Zhi J, Moore R, Kanitra L, Mulligan TE. Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers. J Clin Pharmacol. 2003 Apr;43(4):428-35. Abstract
- ↑ Zhi J, Melia AT, Guerciolini R, Koss-Twardy SG, Passe SM, Rakhit A, Sadowski JA. The effect of orlistat on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. J Clin Pharmacol. 1996 Jul;36(7):659-66. Abstract
- ↑ MacWalter RS, Fraser HW, Armstrong KM. Orlistat enhances warfarin effect. Ann Pharmacother. 2003 Apr;37(4):510-2. Abstract
- ↑ A bitter pill for slimmers? The Guardian. September 25, 2007.
- Xenical homepage from manufacturer, Roche
- Alli homepage from manufacturer, GlaxoSmithKline
- Product information from manufacturer, Roche