Introduction
Xenical (orlistat) is a lipase inhibitor medication approved for weight management in conjunction with a reduced-calorie diet. It represents a unique approach to pharmacologic weight management by acting locally in the gastrointestinal tract rather than systemically.
Mechanism of Action
Xenical exerts its therapeutic effect through inhibition of gastrointestinal lipases, primarily pancreatic lipase. This enzyme is responsible for the hydrolysis of triglycerides into absorbable free fatty acids and monoglycerides. By forming covalent bonds with the active serine residue site of gastric and pancreatic lipases, orlistat inactivates these enzymes. This results in approximately 30% of dietary fat passing through the gastrointestinal tract unabsorbed, thereby reducing caloric intake.
Indications
Xenical is indicated for:
- Obesity management with a body mass index (BMI) ≥30 kg/m²
- Overweight individuals (BMI ≥27 kg/m²) with associated risk factors such as hypertension, type 2 diabetes, or dyslipidemia
- Weight loss maintenance following initial weight reduction
Dosage and Administration
Standard dosing: 120 mg orally three times daily with each main meal containing fat Administration: Should be taken during or up to one hour after meals containing fat Dosing adjustments:- If a meal is missed or contains no fat, the dose may be omitted
- No dosage adjustment required for renal or hepatic impairment
- Not recommended for children under 12 years
Pharmacokinetics
Absorption: Minimal systemic absorption (<2% of dose) Distribution: Primarily confined to gastrointestinal tract; >99% plasma protein binding Metabolism: Primarily within gastrointestinal wall; main metabolites M1 and M3 Elimination: Primarily fecal excretion (≈97%); half-life 1-2 hours Onset of action: Within 24-48 hours of initiationContraindications
- Chronic malabsorption syndrome
- Cholestasis
- Hypersensitivity to orlistat or any component of the formulation
- Pregnancy and breastfeeding
- Organ transplant recipients receiving cyclosporine
Warnings and Precautions
- GI effects: May cause oily spotting, flatus with discharge, fecal urgency
- Fat-soluble vitamin deficiency: May decrease absorption of vitamins A, D, E, K and beta-carotene
- Cholelithiasis: Reported cases of gallstone formation
- Hepatic effects: Rare cases of severe liver injury reported
- Oxalate nephropathy: Cases of increased urinary oxalate reported
- Renal effects: Monitor patients with renal impairment
Drug Interactions
Significant interactions:- Cyclosporine: Decreased absorption; administer at least 2 hours apart
- Warfarin: Monitor INR closely due to potential vitamin K deficiency
- Antidiabetic medications: May require dosage adjustment
- Amiodarone: Possible reduced absorption
- Fat-soluble vitamins: Supplementation recommended
- Levothyroxine: Decreased absorption; administer at least 4 hours apart
- Antiepileptic drugs: Possible reduced absorption
Adverse Effects
Common (≥10%):- Oily spotting
- Flatus with discharge
- Fecal urgency
- Fatty/oily stool
- Oily evacuation
- Increased defecation
- Fecal incontinence
- Abdominal pain/discomfort
- Nausea
- Infectious diarrhea
- Rectal pain/discomfort
- Tooth disorder
- Gum disorder
- Severe liver injury
- Oxalate nephropathy
- Pancreatitis
- Hypersensitivity reactions
- Gallbladder disease
Monitoring Parameters
- Weight and BMI at regular intervals
- Nutritional status and dietary compliance
- Liver function tests (baseline and periodically)
- Renal function in patients at risk
- INR in patients on warfarin therapy
- Vitamin levels (A, D, E, K) with prolonged use
- Blood glucose in diabetic patients
- Blood pressure and lipid profile
Patient Education
- Take with meals containing fat for optimal effect
- Maintain reduced-calorie diet with approximately 30% of calories from fat
- Distribute daily fat intake over three main meals
- Expect common gastrointestinal effects, which may decrease with time
- Take multivitamin containing fat-soluble vitamins once daily at least 2 hours before or after Xenical
- Report severe abdominal pain, yellowing of skin/eyes, or dark urine immediately
- Understand that medication is adjunct to comprehensive weight management program
- Continue regular physical activity program
- Notify all healthcare providers of Xenical use
References
1. FDA Prescribing Information: Xenical (orlistat) capsules. 2019. 2. Torgerson JS, et al. XENDOS study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155-161. 3. Rucker D, et al. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007;335(7631):1194-1199. 4. Sjöström L, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998;352(9123):167-172. 5. Zhi J, et al. Pharmacokinetic evaluation of orlistat. Expert Opin Drug Metab Toxicol. 2015;11(1):151-159. 6. Drew BS, et al. Evaluation of the safety and efficacy of orlistat. Expert Opin Drug Saf. 2007;6(2):175-181.