Usage
- Orlistat is prescribed for weight loss and weight maintenance in adults and adolescents 12 years and older with a body mass index (BMI) ≥ 30 kg/m² (obese) or ≥ 27 kg/m² (overweight) with associated risk factors like hypertension, diabetes, or dyslipidemia. It is used in conjunction with a reduced-calorie and low-fat diet.
- Pharmacological Classification: Lipase inhibitor, anti-obesity agent.
- Mechanism of Action: Orlistat inhibits gastric and pancreatic lipases, enzymes that break down triglycerides (fats) in the intestine. This action prevents the absorption of approximately 30% of ingested fat, which is then eliminated in the feces.
Alternate Names
- International Nonproprietary Name (INN): Orlistat
- Brand Names: Xenical (prescription strength, 120 mg), Alli (over-the-counter, 60 mg)
How It Works
- Pharmacodynamics: Orlistat exerts its therapeutic effect locally in the gastrointestinal (GI) tract. By inhibiting lipases, it reduces the hydrolysis of dietary fats into absorbable free fatty acids and monoglycerides. The unabsorbed fat is then eliminated in the feces, leading to weight loss.
- Pharmacokinetics: Orlistat is minimally absorbed systemically, with less than 1% of an oral dose reaching the bloodstream. It is primarily metabolized in the GI wall and excreted mainly in feces, with a small amount eliminated in urine. Peak fecal fat excretion occurs within 24-48 hours after dosing.
- Mode of Action: Orlistat covalently binds to the serine residue in the active site of gastric and pancreatic lipases, forming a stable complex that prevents the enzyme from interacting with its substrate (dietary triglycerides).
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Orlistat acts through direct enzyme inhibition (lipase inhibition). It does not bind to receptors or modulate neurotransmitters.
- Elimination Pathways: Primarily fecal excretion (as unchanged drug and metabolites), with minor renal excretion.
Dosage
Standard Dosage
Adults:
- Xenical (Prescription): 120 mg orally three times a day with each main meal containing fat (during or up to 1 hour after the meal). Omit dose if a meal is skipped or contains no fat.
- Alli (OTC): 60 mg orally three times a day with each main meal containing fat (during or up to 1 hour after the meal). Omit dose if a meal is skipped or contains no fat.
Children:
- Xenical (Prescription): 120 mg orally three times a day with each main meal containing fat (during or up to 1 hour after the meal) in adolescents 12 years and older. Alli is not approved for pediatric use.
- Pediatric Safety Considerations: Similar GI adverse effects as adults. Monitor vitamin levels and ensure adequate nutrition.
Special Cases:
- Elderly Patients: No specific dose adjustments are typically needed.
- Patients with Renal Impairment: No dose adjustment required.
- Patients with Hepatic Dysfunction: Use with caution in patients with cholestasis.
- Patients with Comorbid Conditions (e.g., Diabetes): Monitor blood glucose levels as weight loss may improve glycemic control, requiring adjustments in diabetes medications.
Clinical Use Cases
Orlistat is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its sole indication is for weight management in conjunction with lifestyle modifications.
Dosage Adjustments
No specific dose adjustments are required based on renal or hepatic dysfunction. However, careful monitoring is advised in patients with cholestasis.
Side Effects
Common Side Effects:
- Oily or fatty stools (steatorrhea)
- Oily spotting
- Flatulence with discharge
- Fecal urgency
- Increased defecation
- Abdominal pain/discomfort
Rare but Serious Side Effects:
- Liver injury (hepatitis)
- Oxalate nephropathy (kidney stones)
- Severe allergic reactions
Long-Term Effects:
- Potential for fat-soluble vitamin deficiencies (A, D, E, and K) with prolonged use.
- Cholelithiasis (gallstones) has been reported rarely.
Adverse Drug Reactions (ADR):
- Hepatotoxicity (rare but serious)
- Acute renal failure (secondary to oxalate nephropathy)
- Hypersensitivity reactions
Contraindications
- Chronic malabsorption syndrome
- Cholestasis
- Pregnancy
- Hypersensitivity to orlistat
Drug Interactions
- Warfarin: Reduced vitamin K absorption, increasing INR. Monitor coagulation parameters.
- Cyclosporine: Reduced cyclosporine levels. Administer cyclosporine 3 hours after orlistat.
- Levothyroxine: Reduced levothyroxine absorption. Administer 4 hours apart. Monitor thyroid function.
- Antiepileptic drugs (AEDs): Potential for decreased AED levels. Monitor AED serum levels.
- Antiretroviral drugs: Potential for decreased antiretroviral drug levels.
- Fat-soluble vitamins (A, D, E, and K): Reduced absorption. Take a multivitamin supplement at least 2 hours before or after orlistat.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (Contraindicated)
- Fetal Risks: Orlistat is contraindicated during pregnancy. Weight loss during pregnancy is not recommended.
- Breastfeeding: Orlistat is present in breast milk. It is not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits gastric and pancreatic lipases, reducing dietary fat absorption.
- Side Effects: Primarily gastrointestinal (oily stools, flatulence, fecal urgency). Rarely, liver injury and kidney stones.
- Contraindications: Chronic malabsorption, cholestasis, pregnancy, hypersensitivity.
- Drug Interactions: Warfarin, cyclosporine, levothyroxine, AEDs, antiretrovirals, fat-soluble vitamins.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy and not recommended during breastfeeding.
- Dosage: Adults/Adolescents (≥12 years): Xenical 120 mg TID with meals. Alli 60 mg TID with meals.
- Monitoring Parameters: Weight, BMI, blood glucose (in diabetics), liver function tests, INR (if on warfarin), AED levels (if applicable), vitamin levels (A, D, E, and K).
Popular Combinations (Not typically combined with other weight-loss medications)
Precautions
- Assess for chronic malabsorption, cholestasis, and pregnancy before initiating therapy.
- Advise patients on a reduced-calorie, low-fat diet (30% of calories from fat).
- Recommend a multivitamin supplement containing fat-soluble vitamins taken at least 2 hours before or after orlistat.
- Monitor for GI adverse effects, liver function, and kidney function.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Orlistat?
A: Xenical: Adults and adolescents 12 years and older: 120 mg TID with meals. Alli: Adults only: 60 mg TID with meals.
Q2: How does Orlistat work?
A: Orlistat inhibits pancreatic and gastric lipases, reducing the absorption of dietary fat by about 30%.
Q3: What are the common side effects of Orlistat?
A: The most common side effects are gastrointestinal, including oily stools, flatulence, fecal urgency, and oily spotting.
Q4: Who should not take Orlistat?
A: Patients with chronic malabsorption, cholestasis, or hypersensitivity to orlistat. It is also contraindicated in pregnancy.
Q5: Does Orlistat interact with other medications?
A: Yes, it can interact with warfarin, cyclosporine, levothyroxine, antiepileptic drugs, and fat-soluble vitamins.
Q6: Can Orlistat be used during pregnancy or breastfeeding?
A: No, it’s contraindicated during pregnancy and not recommended during breastfeeding.
Q7: What are the long-term effects of taking Orlistat?
A: Potential long-term effects include possible deficiencies in fat-soluble vitamins and, rarely, gallstones. Regular monitoring of vitamin levels is advised.
Q8: Are there any dietary restrictions when taking Orlistat?
A: Yes, a reduced-calorie, low-fat diet (30% of daily calories from fat) is crucial for optimal results and minimizing GI side effects.
Q9: How long does it take for Orlistat to start working?
A: The effects on fecal fat excretion can be seen within 24-48 hours, but clinically significant weight loss may take several weeks.
Q10: What should I monitor in patients taking Orlistat?
A: Monitor weight, BMI, blood glucose (in diabetics), liver function tests, INR (if on warfarin), AED levels (if applicable), and vitamin levels (A, D, E, and K).
