Orlistat exerts its therapeutic effects through its action on gastrointestinal lipases. Its key mechanisms include:

1. Inhibition of Lipases:
   • Orlistat is a potent inhibitor of gastric and pancreatic lipases, enzymes responsible for the breakdown of dietary fats into absorbable free fatty acids and monoglycerides.
   • By inhibiting these lipases, orlistat prevents the hydrolysis of triglycerides, reducing the absorption of dietary fats by approximately 30%.
2. Reduction of Caloric Intake:
   • The undigested fats are excreted in the feces, leading to a reduction in caloric intake and promoting weight loss.
3. Improvement of Metabolic Parameters:
   • Orlistat has been shown to improve metabolic parameters such as blood pressure, cholesterol levels, and glycemic control in obese patients.

Orlistat is approved for specific clinical conditions, including:

1. Obesity:
   • Management of obesity in adults with a BMI of 30 kg/m² or higher.
   • Management of obesity in adults with a BMI of 28 kg/m² or higher with associated risk factors such as hypertension, diabetes, or hyperlipidemia.
2. Weight Maintenance:
   • Prevention of weight regain after initial weight loss.
3. Off-Label Uses:
   • Adjunctive therapy for weight loss in patients undergoing bariatric surgery.

The dosage of orlistat varies depending on the formulation and patient response. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

1. Adults:
   • Prescription Strength (120 mg): 120 mg three times daily with each main meal containing fat.
   • Over-the-Counter (60 mg): 60 mg three times daily with each main meal containing fat.

Important Considerations:

• Orlistat should be taken during or up to 1 hour after a meal.
• If a meal is missed or contains no fat, the dose of orlistat should be omitted.
• A balanced, reduced-calorie diet containing approximately 30% of calories from fat is recommended to minimize gastrointestinal side effects.

Orlistat is generally well-tolerated, but it is associated with a range of side effects, particularly related to its mechanism of action. Common side effects include:

1. Gastrointestinal:
   • Oily spotting, flatulence with discharge, fecal urgency, and fatty/oily stools.
   • Increased frequency of bowel movements and fecal incontinence.
2. Other:
   • Headache and abdominal pain.

Serious Side Effects:

• Hepatotoxicity: Rare cases of severe liver injury have been reported.
• Hypersensitivity Reactions: Rash, itching, and anaphylaxis (rare).

Orlistat requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Gastrointestinal Effects:
   • Patients should be advised to follow a low-fat diet to minimize gastrointestinal side effects.
2. Fat-Soluble Vitamin Deficiency:
   • Orlistat may reduce the absorption of fat-soluble vitamins (A, D, E, and K). Consider supplementation with a multivitamin containing these vitamins, taken at least 2 hours before or after orlistat.
3. Pregnancy and Lactation:
   • Orlistat should be avoided during pregnancy and breastfeeding due to the potential risk of fat-soluble vitamin deficiency in the infant.
4. Renal Impairment:
   • Use with caution in patients with impaired kidney function. Monitor renal function regularly.
5. Elderly Patients:
   • No dose adjustment is required, but caution is advised due to potential comorbidities.

Orlistat has a moderate potential for drug interactions due to its effects on fat absorption. Key interactions include:

1. Fat-Soluble Vitamins:
   • Orlistat may reduce the absorption of fat-soluble vitamins (A, D, E, and K). Consider supplementation.
2. Cyclosporine:
   • Orlistat may reduce the absorption of cyclosporine, decreasing its efficacy. Monitor cyclosporine levels closely.
3. Levothyroxine:
   • Orlistat may reduce the absorption of levothyroxine, decreasing its efficacy. Administer levothyroxine at least 4 hours before or after orlistat.
4. Anticoagulants:
   • Orlistat may reduce the absorption of vitamin K, increasing the risk of bleeding in patients on warfarin. Monitor INR closely.
5. Antiepileptics:
   • Orlistat may reduce the absorption of antiepileptic drugs, decreasing their efficacy. Monitor seizure control closely.

Orlistat is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Xenical (a well-known brand for the prescription-strength 120 mg formulation).
• Alli (a well-known brand for the over-the-counter 60 mg formulation).
• Orlistat Accord.
• Orlistat Mylan.