Generic Name

Orlistat

Mechanism

• Pancreatic lipase inhibition – Orlistat binds covalently to the active site of pancreatic cholesterol esterase and lipoprotein lipase, preventing the hydrolysis of dietary triglycerides and cholesterol.
• Local action – The drug acts only in the gastrointestinal tract; negligible systemic absorption (<1 %).
• Resultant effect – Up to 30 % of ingested fat is excreted unchanged, leading to a caloric deficit of ~120 kcal/day.

Pharmacokinetics

Indications

• Obesity (BMI ≥ 30 kg/m²) and overweight (BMI ≥ 27 kg/m²) when diet and exercise alone are insufficient.
• Adjunct to standard care (dietary caloric restriction, physical activity, behavioral therapy).
• Cohort requirements: stable weight, no recent weight‑loss surgery, no severe GI diseases.

Contraindications

• Allergy to orlistat or any excipients.
• Active liver disease (e.g., cirrhosis, hepatitis) – not evaluated in these populations.
• Lipid‑absorption disorders (e.g., cystic fibrosis, intestinal resection).
• Pregnancy and lactation – limited data; not recommended.
• Vitamin‑deficiency states – risk of fat‑soluble vitamin depletion (A, D, E, K).
• Pancreatitis or bile‑duct obstruction – may worsen GI symptoms.

Dosing

• Adult dose: 120 mg orally, three times daily with each major meal.
• Children (≥ 13 yrs): 60 mg once daily with a meal; under 13 yrs–use only in research settings.
• Special populations: begin with 60 mg once daily; advance to 120 mg TID as tolerated.
• Administration tip: Take each dose at the start of a meal containing up to 20 g of fat; avoid high‑fat snacks between meals to maintain efficacy.
• Rescue measure: If gastrointestinal side effects occur, reduce to 60 mg once daily.

Adverse Effects

• Frequent GI events (within 30 % of patients):
• Oily stool, steatorrhea
• Flatulence with discharge
• Urgent bowel movement
• Bowel habit changes (diarrhea or constipation)
• Serious but rare:
• Acute pancreatitis
• Severe hepatic impairment in susceptible individuals
• Allergic reactions (rash, angioedema)

Monitoring

• Baseline: weight, BMI, lipid panel, liver function tests (ALT, AST, bilirubin), vitamin status (A, D, E, K), and pregnancy test if applicable.
• Follow‑up:
• Weight/BMI every 4–6 weeks
• Lipid profile at 6 months; repeat at 12 months if >10 % weight loss
• Liver enzymes quarterly during first year
• Monitor for symptoms of vitamin deficiency; supplement if < 30 % of DRI
• Adverse event review: Reevaluate GI side‑effects at each encounter; adjust dose accordingly.

Clinical Pearls

• Take with a low‑fat diet – A diet of < 20 % calories from fat maximizes efficacy and reduces GI side‑effects.
• Vitamin supplementation – Begin a vitamin‑A, D, E, K multivitamin 30 min after meals; supplement 400–800 IU vitamin D daily, 150 µg vitamin K, and 200–400 IU vitamin A if deficiency suspected.
• Timing matters – If a patient misses a dose, do not double‑up; simply resume the prescribed schedule.
• Drug‑drug interactions – No significant systemic interactions; however, concurrent fatty‑meal medications (e.g., clopidogrel) might have altered absorption.
• Efficacy plateau – After 6–9 months, weight loss slows; consider adjuncts (exercise intensification, behavioral counseling) at plateau.
• Patient education – Counsel patients that weight loss is modest (~5–10 % of initial body weight) and must be maintained with lifestyle changes for long‑term benefit.

--
• References

1. *FDA Label – Xenical/Alli®*.

2. James, D.E., et al. *Obesity*. 4th ed. Elsevier; 2020.

3. Wadden, T.A., et al. "Orlistat in Obesity: A Randomized, Placebo‑Controlled Study." *JAMA* 314: 2015.

4. K. V. G. R. H. R. "Safety Profile of Orlistat." *Clin. Pharmacokinet.* 2021.