What is the recommended dosage of orlistat (Xenical) for weight loss?

Orlistat Dosage

The recommended dose of orlistat is 120 mg taken orally three times daily with each main meal containing fat, though the 2022 AGA guidelines conditionally recommend against its routine use due to modest efficacy and significant gastrointestinal side effects. 1, 2

Standard Dosing Regimen

• Take one 120 mg capsule (prescription Xenical) three times daily with each main meal containing fat 1, 2
• The dose can be omitted if a meal is very low in fat or skipped entirely 1
• An over-the-counter formulation (Alli) is available at 60 mg three times daily, which blocks approximately 25% of dietary fat absorption compared to 30% with the 120 mg dose 3, 4
• The 60 mg dose has approximately 85% of the efficacy of the 120 mg dose for weight loss 3

Mandatory Dietary Requirements

• Patients must follow a diet with approximately 30% of calories from fat to minimize gastrointestinal side effects 1, 2
• A hypocaloric diet with 500-800 kcal/day deficit should be implemented alongside orlistat 1, 2
• Consuming less than 30% of energy from fat significantly reduces gastrointestinal adverse effects 3

Required Vitamin Supplementation

• All patients taking orlistat must take a daily multivitamin containing fat-soluble vitamins (A, D, E, K) at bedtime, at least 2 hours apart from orlistat doses 1, 2, 5
• This supplementation is mandatory because orlistat blocks approximately 30% of dietary fat absorption, leading to potential deficiencies in fat-soluble vitamins 1, 2

Critical Drug Interactions Requiring Dose Separation

• Separate orlistat from cyclosporine by at least 3 hours; orlistat should not be co-administered with cyclosporine 1, 2
• Levothyroxine and warfarin require longer intervals between doses and closer monitoring when taken with orlistat 2
• Orlistat should not be taken with antiepileptic drugs 1

Expected Efficacy

• Over 48 weeks to 4 years, orlistat produces approximately 2.8 kg (2.78% total body weight loss) more than placebo 1, 2
• Patients are 1.71 times more likely to achieve 5% total body weight loss and 1.94 times more likely to achieve 10% total body weight loss compared to placebo 1
• Most weight loss occurs in the first 6 months of treatment 5

Common Adverse Effects and Tolerability

• Gastrointestinal side effects are the primary adverse events, including oily spotting, flatulence with discharge, fecal urgency, and fecal incontinence 1, 4
• Treatment discontinuation due to GI adverse effects is 2.86 times higher than placebo 1, 2
• These GI effects are transient and can be minimized by adhering to a low-fat diet 1, 3

Serious Safety Considerations

• The FDA has documented 12 cases of liver failure in patients outside the United States on orlistat 120 mg and 1 case with the 60 mg dose 1, 2
• Orlistat is contraindicated in pregnancy, chronic malabsorption syndrome, and cholestasis 1, 2

Clinical Context and Guideline Recommendation

• The 2022 AGA guidelines make a conditional recommendation against the use of orlistat for individuals with obesity or overweight with weight-related complications 1, 2
• However, a small minority of patients who highly value even modest weight loss and can tolerate GI effects may reasonably choose orlistat treatment 1, 2
• The modest efficacy (2.8 kg weight loss) combined with high rates of GI side effects and treatment discontinuation led to this recommendation against routine use 1, 2