OBETAS -120MG

Indications

• Obesity
• Weight management
• Adjunct in obesity treatment alongside a reduced-calorie diet

Dosage

Children: Orlistat is not recommended for use in children under 12 years of age. For children aged 12 years and older, refer to the BNF for Children for specific dosing guidelines.

Adults: The usual dose of Orlistat is 120 mg taken three times daily with each main meal containing fat. If a meal is missed or contains no fat, the dose should be omitted.

Mechanism of action

Orlistat is a potent and selective inhibitor of gastric and pancreatic lipases, which are enzymes responsible for fat metabolism. It works by covalently binding to the serine residues at the active site of these enzymes. This action inhibits the hydrolysis of triglycerides into absorbable free fatty acids and monoglycerides, resulting in the excretion of undigested fats. Consequently, orlistat decreases the caloric intake from fats by approximately 30%, contributing to weight loss and weight maintenance without systemic absorption.

Pharmacodynamics

Orlistat aids in weight reduction and maintenance by preventing dietary fat absorption through the inhibition of lipase enzymes. This leads to a caloric deficit that can positively impact weight control. The drug exhibits antiobesity and antilipemic effects, making it suitable for patients aiming to lose weight or maintain weight loss.

Pharmacokinetics

Orlistat is not significantly absorbed systemically, as its action occurs in the gastrointestinal lumen. It is minimally absorbed (less than 1%) with a plasma half-life of approximately 1 to 2 hours. The majority of the drug is excreted unchanged in feces, which contributes to its mechanism of action as it acts locally within the GI tract without requiring systemic circulation.

Contra-indications

• Cholestasis
• Chronic malabsorption syndrome
• Pregnancy

Adverse effects

• Gastrointestinal discomfort
• Abdominal pain
• Diarrhoea
• Fatty/oily stools
• Rectal urgency
• Flatulence
• Headaches
• Nausea
• Vomiting

Interactions

• May affect absorption of fat-soluble vitamins
• May interact with anticoagulants (e.g., warfarin)

Precautions

• Caution in patients with chronic kidney disease
• Monitor for signs of vitamin deficiency
• Monitor weight and nutritional status during treatment

Pregnancy

No evidence of teratogenicity in animal studies, but lack of information in pregnant women. Weight loss during pregnancy may cause fetal harm.

Breast-feeding

Avoid; present in milk in animal studies.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• 60 mg capsules (Alli)
• 120 mg capsules (Orlistat)

Mechanism of action

Orlistat is a potent and selective inhibitor of various lipase enzymes responsible for the metabolism of fat. It acts in the gastrointestinal (GI) tract via covalent binding to the serine residues located on the active site of both gastric and pancreatic lipase. When orlistat is taken with food containing fat, it partially inhibits the hydrolysis of triglycerides. This decreases absorption of monoaclglycerides and free fatty acids, contributing to weight maintenance and weight loss. Orlistat is a reversible inhibitor of lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine residue site of gastric and pancreatic lipases. The inactivated enzymes are thus unavailable to hydrolyze dietary fat in the form of triglycerides into absorbable free fatty acids and monoglycerides. As undigested triglycerides are not absorbed, the resulting caloric deficit may have a positive effect on weight control. Systemic absorption of the drug is therefore not needed for activity. At the recommended therapeutic dose ... orlistat inhibits dietary fat absorption by approximately 30%. Orlistat, a reversible inhibitor of gastric and pancreatic lipases, exhibits antiobesity and antilipemic activity. The drug also inhibits certain other (e.g., microbial, carboxylester [for hydrolysis of vitamin esters]) lipases. Orlistat is a synthetic derivative of naturally occurring lipstatin. Unlike most other currently available antiobesity agents, orlistat does not exert anorexigenic (appetite suppressant) effects. Instead, orlistat exerts its antiobesity effect by decreasing the absorption of dietary fats (triacylglycerols) in the intestinal lumen via inhibition of triglyceride hydrolysis; at recommended dosages, approximately one-third of dietary fat will not be absorbed. By preventing triglyceride hydrolysis, the drug decreases intestinal concentrations of absorbable free fatty acids and monoglycerides. Orlistat, an antiobesity drug, is cytostatic and cytotoxic to tumor cells. The antitumor activity of orlistat can be attributed to its ability to inhibit the thioesterase domain of fatty acid synthase (FAS). The objective of the present study was to test the effect of orlistat on endothelial cell proliferation and angiogenesis. Orlistat inhibits endothelial cell FAS, blocks the synthesis of fatty acids, and prevents endothelial cell proliferation. More significantly, orlistat inhibits human neovascularization in an ex vivo assay, which suggests that it may be useful as an antiangiogenic drug. The mechanism of these effects can be traced to the fact that orlistat prevents the display of the vascular endothelial growth factor (VEGF) receptor (VEGFR2/KDR/Flk1) on the endothelial cell surface. Thus, orlistat is an antiangiogenic agent with a novel mechanism of action.

Pharmacodynamics

Orlistat helps with weight reduction and maintenance by inhibiting the absorption of dietary fats via the inhibition of lipase enzymes.