What are the contraindications for orlistat (Xenical) and alternative weight loss medications?

Contraindications for Orlistat (Xenical) and Alternative Weight Loss Medications

Orlistat (Xenical) is contraindicated in pregnancy, chronic malabsorption syndrome, cholestasis, and in patients who have had organ transplants. 1, 2

Orlistat (Xenical) Contraindications

Absolute Contraindications:

• Pregnancy and breastfeeding 1, 2
• Chronic malabsorption syndrome 1
• Cholestasis 1
• Organ transplantation (interferes with anti-rejection medications) 2

Medication Interactions and Precautions:

• Should not be taken with cyclosporine (decreased absorption) 1
• Levothyroxine (decreased absorption - administer 4 hours apart) 1, 2
• Warfarin (enhanced effect - requires monitoring) 1, 2
• Antiepileptic drugs (decreased effectiveness) 1, 2
• Amiodarone (decreased absorption) 2, 3
• Antiretrovirals (potential decreased effectiveness) 2

Additional Precautions:

• Cholelithiasis (gallstones) 1, 2
• Nephrolithiasis (kidney stones) 1, 2
• History of pancreatitis 2
• Liver disease (rare cases of severe liver injury reported) 1, 4

Alternative Weight Loss Medications and Their Contraindications

Phentermine

• Contraindicated in: 1
  • Anxiety disorders and agitated states
  • History of heart disease
  • Uncontrolled hypertension
  • Seizure disorders
  • During or within 14 days of MAOIs
  • Pregnancy and breastfeeding
  • Hyperthyroidism
  • Glaucoma
  • History of drug abuse
  • Concomitant use with other sympathomimetic amines

Phentermine/Topiramate Extended Release (Qsymia)

• Contraindicated in: 1
  • Pregnancy (risk of birth defects)
  • Glaucoma
  • Hyperthyroidism
  • During or within 14 days of MAOIs
  • Concomitant use with other sympathomimetic amines

Naltrexone/Bupropion (Contrave)

• Contraindicated in: 1
  • Pregnancy
  • Uncontrolled hypertension
  • Seizure disorders or risk of seizures
  • Bulimia or anorexia
  • Use of opioid agonists or partial agonists
  • During or within 14 days of MAOIs

Liraglutide (Saxenda)

• Contraindicated in: 1
  • Pregnancy
  • Personal or family history of medullary thyroid carcinoma
  • Multiple endocrine neoplasia syndrome type 2
  • History of pancreatitis

Clinical Considerations for Orlistat Use

Dosing and Administration:

• Available as 120 mg prescription (Xenical) or 60 mg over-the-counter (Alli) 1
• Taken three times daily with meals containing fat 1
• Can omit dose if meal is very low in fat 1
• Recommend daily multivitamin containing vitamins A, D, E, and K taken at bedtime or 2 hours after orlistat dose 1, 2

Efficacy:

• Produces modest weight loss of 2.78% total body weight loss compared to placebo 1
• Approximately 2.81 kg greater weight loss than placebo 1
• Patients on orlistat are 1.71 times more likely to achieve 5% weight loss and 1.94 times more likely to achieve 10% weight loss compared to placebo 1

Side Effects:

• Common gastrointestinal side effects: 1, 2
  • Steatorrhea (oily stools)
  • Fecal urgency and incontinence
  • Flatulence with discharge
  • Oily spotting
  • Frequent bowel movements
  • Abdominal pain
• Rare but serious adverse effects:
  • Liver injury (12 cases of liver failure reported outside US with 120 mg dose, 1 case with 60 mg dose) 1, 4
  • Acute kidney injury (rare cases reported) 3
  • Cholelithiasis (gallstones) 1

Algorithm for Weight Loss Medication Selection

1. First-line options for patients without cardiovascular disease:

   • GLP-1 receptor agonists (e.g., semaglutide, liraglutide) for patients with diabetes 1
   • Phentermine (short-term use ≤12 weeks) for rapid initial weight loss 1

2. First-line options for patients with cardiovascular disease:

   • Lorcaserin or orlistat (safer alternatives to sympathomimetics) 1
   • GLP-1 receptor agonists (if approved for obesity in your region) 1

3. For patients with type 2 diabetes:

   • GLP-1 receptor agonists or SGLT-2 inhibitors (promote both weight loss and glycemic control) 1
   • Metformin (first-line agent for T2DM with modest weight benefits) 1

4. For patients with gastrointestinal conditions:

   • Avoid orlistat in patients with chronic malabsorption, inflammatory bowel disease, celiac disease, or history of bariatric surgery 1
   • Consider phentermine or GLP-1 agonists as alternatives 1

5. Monitoring recommendations:

   • Assess efficacy and safety monthly for first 3 months, then every 3 months 1
   • If <5% weight loss at 12 weeks, consider discontinuing medication and trying alternative 1
   • Monitor for vitamin deficiencies in patients on orlistat 1, 2
   • Monitor drug interactions, particularly with anticoagulants, thyroid medications, and anticonvulsants 2, 3