What are the side effects of orlistat (xenical) when used for weight loss?

Orlistat Side Effects in Weight Loss Treatment

Orlistat causes significant gastrointestinal side effects in 70-80% of users, including oily spotting, fecal urgency, flatulence with discharge, and fecal incontinence, which are directly related to its mechanism of blocking fat absorption. 1

Primary Side Effects

Gastrointestinal Effects

• Oily spotting/stool - Most common side effect
• Fecal urgency - Difficulty controlling bowel movements
• Flatulence with discharge - Gas with oily spotting
• Fecal incontinence - Involuntary leakage of stool
• Increased defecation frequency - More frequent bowel movements
• Abdominal pain - Related to digestive disturbances

These gastrointestinal events typically:

• Occur early in treatment (within first 4 weeks)
• Are mild to moderate in intensity
• Usually limited to 1-2 episodes
• Often resolve despite continued treatment 1

Approximately 4% of patients discontinue orlistat due to these gastrointestinal complaints, compared to 1% with placebo 1.

Nutritional Effects

• Decreased absorption of fat-soluble vitamins (A, D, E, K)
  • Most remain within normal range but can occasionally drop below reference range
  • Requires supplementation with a daily multivitamin taken at bedtime or at least 2 hours separate from orlistat 2, 3

Serious Side Effects (Rare)

Liver Effects

• Potential liver injury - FDA has added a label warning 2
• Signs to monitor: Itching, yellow eyes/skin, dark urine, loss of appetite 3

Severe Abdominal Pain

• May indicate a serious medical condition requiring immediate attention 3

Drug Interactions

Orlistat can significantly affect absorption of lipophilic medications when taken simultaneously:

• Cyclosporine - Documented subtherapeutic levels in transplant recipients 1
• Anticoagulants (blood thinners) 3
• Amiodarone (heart medicine) 3
• Antiepileptic drugs - May affect seizure control 3
• Antiretrovirals (HIV medications) 3
• Thyroid medications 3

Important: Lipophilic medications should be taken at least 2 hours before or after orlistat, and drug levels should be monitored when appropriate 1, 2.

Contraindications

Orlistat should not be used in patients with:

• Organ transplants
• Chronic malabsorption syndrome
• Cholestasis
• Gallstones
• Pregnancy or breastfeeding
• Hypersensitivity to orlistat or its components 2, 3

Minimizing Side Effects

1. Follow a reduced-calorie, low-fat diet (≤30% of calories from fat)
2. Take orlistat during or within 1 hour after meals containing fat
3. Skip the dose if the meal contains no fat or is skipped
4. Add fiber supplements to help manage gastrointestinal symptoms
5. Take a daily multivitamin at bedtime (at least 2 hours after last orlistat dose) 1, 2

Monitoring Recommendations

• Regular assessment of gastrointestinal symptoms
• Periodic liver function monitoring
• Evaluation of fat-soluble vitamin levels if treatment extends beyond short-term use
• Monitoring of medication levels for patients on concurrent lipophilic drugs 1, 2

The American Gastroenterological Association suggests against routine use of orlistat due to modest weight loss benefits relative to the significant gastrointestinal side effects 2.