Products
Orlistat is available in many countries in the form of capsules and has been approved since 1998 (Xenical, 120 mg, Roche Pharmaceuticals). In 2009, it was also approved for self-medication after specialist consultation with healthcare professionals without a doctor’s prescription at half the dosage (Alli, 60 mg, GlaxoSmithKline). The generic Xenical drug Orlistat Sandoz 120 was approved in December 2011. Calobalin Sandoz (60 mg) went on sale in summer 2012. In fall 2012, Alli was withdrawn from the market again due to supply difficulties.
Structure and properties
Orlistat (= tetrahydrolipstatin, C29H53NO5, Mr = 495.73 g/mol) is a chemically slightly modified natural product. It is a stable and saturated dervate of lipstatin, a naturally occurring lipase inhibitor from . It exists as a white crystalline powder that is lipophilic and practically insoluble in water.
Effects
Orlistat (ATC A08AB01) is a lipase inhibitor that inhibits fat digestion in the stomach and upper small intestine, reducing dietary fat absorption by approximately 30% (60 mg: approximately 25%). Triglycerides can no longer be broken down by lipases into fatty acids and monoglycerides. As a result, the fat from food cannot be absorbed and is excreted undigested. Orlistat acts locally in the intestine, is hardly absorbed, has no effects in the central nervous system and cannot be misused as a stimulant. It is also called the “antabuse for overweight people” because, due to the possible adverse effects, fat can in fact only be taken in small quantities during treatment. Unlike the numerous dietary supplements on the market as slimming products, Orlistat is scientifically and clinically very well studied. Users can lose up to 50% more weight than with diet alone. So if you lose 4 kg, you can reduce your weight by up to an additional 2 kg with Orlistat.
Mechanism of action
Hydrolysis of triglycerides relies on an interaction with the Active Site of lipases, which contains a catalytic triad with the amino acid serine. Orlistat is a β-lactone that covalently binds this serine and irreversibly inhibits the digestive enzyme. It is selective for lipases (e.g., pancreatic lipase, gastric lipase) and does not inhibit other digestive enzymes such as trypsin or chymotrypsin.
Indications
Overweight and obesity (BMI ≥ 28 kg/m2), along with a low-fat, low-calorie diet.
Dosage
As directed in the package insert. The usual dose is 27 mg, 60 mg, or 120 mg 3 times daily. The capsules or chewable tablets are taken either immediately before, during, or up to one hour after a meal. If the meal does not contain fat, the dose may be omitted. The meal taken at the same time may contain about 15 g of fat.
Contraindications
- Hypersensitivity
- Chronic malabsorption syndrome
- Cholestasis (bile stasis)
- Concurrent treatment with ciclosporin
- Pregnancy and lactation
Full details of precautions and interactions can be found in the drug label.
Interactions
Drug-drug interactions are possible with ciclosporin, amiodarone, vitamin K antagonists, and antiepileptic drugs. Absorption of ciclosporin and amiodarone is inhibited. Orlistat may reduce the absorption of fat-soluble vitamins (A, D, E, K). Taking a multivitamin may be considered. It is recommended to take it before bedtime. When diarrhea occurs as an adverse effect, the protection of oral contraceptives may be reduced.
Adverse effects
The most common adverse effects include unpleasant digestive symptoms such as a discharge of oily secretions, flatulence with discharge of stools, urge to defecate, oily or greasy stools, increased bowel movements, lower abdominal pain, thin stools, and incontinence. These effects can be reduced by a low-fat diet. Other possible side effects include dental discomfort, gum discomfort, flu, anxiety, headaches, respiratory infections, urinary tract infections, menstrual irregularities, fatigue, and hypersensitivity reactions.Isolated cases of cholestatic liver inflammation (hepatitis), jaundice, hepatocellular necrosis, liver failure, gallstones, elevation of liver enzymes (transaminases, alkaline phosphatase), and cases of pancreatitis (inflammation of the pancreas) have been reported. The exact mechanism is not known and the relationship has not been conclusively proven.
