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Pronunciation
(OR li stat)
Generic Available (U.S.)
No
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Management of obesity, including weight loss and weight management, when used in conjunction with a reduced-calorie and low-fat diet; reduce the risk of weight regain after prior weight loss; indicated for obese patients with an initial body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (eg, diabetes, dyslipidemia, hypertension)
Pregnancy Risk Factor
X
Pregnancy Considerations
Adverse events were not observed in animal reproduction studies. Although orlistat is minimally absorbed, weight-loss therapy is not recommended for pregnant women. Obese and overweight women should be encouraged to participate in weight reduction programs prior to attempting pregnancy; weight gain during pregnancy should be determined by their prepregnancy BMI and current guidelines (ADA, 2009; IOM, 2009). Use of orlistat is contraindicated in pregnant women.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Weight-loss therapy is generally not recommended for lactating women. Weight-loss programs which include physical activity and nutrition components should be discussed at the 6-week postpartum visit (ADA, 2009; IOM, 2009).
Contraindications
Hypersensitivity to orlistat or any component of the formulation; chronic malabsorption syndrome or cholestasis; pregnancy
Warnings/Precautions
Concerns related to adverse effects:
• Cholelithiasis: In general, substantial weight loss may increase the risk of cholelithiasis.
• Hepatotoxicity: Cases of severe liver injury (some fatal) with hepatocellular necrosis or acute hepatic failure have been reported (rare); liver transplantation has been required in some patients. Patients should be instructed to report any symptoms of hepatic dysfunction (eg, anorexia, pruritus, jaundice, dark urine, light colored stools, right upper quadrant pain); discontinue orlistat and obtain liver function test immediately if symptoms occur.
• Increased urinary oxalate: Increased levels of urinary oxalate following treatment may occur in some patients; monitor renal function in patients at risk for renal failure; use with caution in patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis.
Disease-related concerns:
• Diabetes: Monitor patients with diabetes closely; dosage adjustments of antidiabetic medications may be necessary.
Concurrent drug therapy issues:
• Cyclosporine: Orlistat may decrease cyclosporine plasma concentrations; administer cyclosporine ≥3 hours before or after orlistat and monitor frequently.
Special populations:
• Pediatrics: When used in adolescents, weight related to growth is accounted for in BMI, therefore, reduction in BMI is a better indicator of weight loss.
Other warnings/precautions:
• Appropriate use: Prior to use other causes for obesity (eg, hypothyroidism) should be ruled out.
• Dietary guidelines: Patients should be advised to adhere to dietary guidelines; if taken with a diet high in fat (>30% total daily calories from fat), gastrointestinal adverse events may increase. Distribute daily fat intake over 3 main meals. If taken with any 1 meal very high in fat, the possibility of gastrointestinal effects increases. Counsel patients to take a multivitamin supplement that contains fat-soluble vitamins ≥2 hours before or after orlistat administration to ensure adequate nutrition; orlistat has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene.
• Potential for misuse: The potential exists for misuse in inappropriate patient populations (eg, patients with anorexia nervosa or bulimia) similar to any weight loss agent.
• Self-medication (OTC use): Prior to use, patients should contact their healthcare provider if they have ever had kidney stones, gall bladder disease, or pancreatitis. Patients taking medications for diabetes or thyroid disease, anticoagulants, or other weight-loss products should consult their healthcare provider or pharmacist. Patients who have had an organ transplant should not use orlistat. If severe and/or continuous abdominal pain, itching, yellowing of the eyes or skin, dark urine, or loss of appetite occurs, use should be discontinued and healthcare provider consulted.
Adverse Reactions
Note: The frequency of most adverse reactions (especially gastrointestinal effects) decreases over time.
>10%:
Central nervous system: Headache (≤31%)
Gastrointestinal: Oily spotting (4% to 27%), abdominal pain/discomfort (≤26%), flatus with discharge (2% to 24%), fecal urgency (3% to 22%), fatty/oily stool (6% to 20%), oily evacuation (2% to 12%), defecation increased (3% to 11%)
Neuromuscular & skeletal: Back pain (≤14%)
Respiratory: Upper respiratory infection (26% to 38%)
Miscellaneous: Influenza (≤40%)
1% to 10%:
Cardiovascular: Pedal edema (≤3%)
Central nervous system: Fatigue (3% to 7%), anxiety (3% to 5%), sleep disorder (≤4%)
Dermatologic: Dry skin (≤2%)
Endocrine & metabolic: Menstrual irregularities (≤10%)
Gastrointestinal: Nausea (4% to 8%), fecal incontinence (2% to 8%), infectious diarrhea (≤5%), rectal pain/discomfort (3% to 5%), tooth disorder (3% to 4%), gingival disorder (2% to 4%)
Genitourinary: Urinary tract infection (6% to 8%), vaginitis (3% to 4%)
Neuromuscular & skeletal: Myalgia (≤4%)
Otic: Otitis (3% to 4%)
Respiratory: Lower respiratory infection (≤8%)
<1%, postmarketing, and/or case reports: Abdominal distension (in patients with diabetes), alkaline phosphatase increased, anaphylaxis, angioedema, bronchospasm, bullous eruption, cholelithiasis (may be caused by weight loss), coagulation parameters altered (concurrent use with warfarin), gastrointestinal bleeding (lower), hepatic failure, hepatitis, hypersensitivity, hypoglycemia (in patients with diabetes), hypothyroidism (concurrent use with levothyroxine), kidney injury (acute), oxalate nephropathy, pancreatitis, pruritus, rash, transaminases increased, urinary oxalate levels increased, urticaria
Metabolism/Transport Effects
None known.
Drug Interactions
Amiodarone: Orlistat may decrease the absorption of Amiodarone. Risk C: Monitor therapy
CycloSPORINE: Orlistat may decrease the serum concentration of CycloSPORINE. Management: Administer orlistat at least 3 hours before or after oral cyclosporine. Monitor for decreased serum concentrations of oral cyclosporine even with the recommended dose separation. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Orlistat may decrease the serum concentration of CycloSPORINE (Systemic). Management: Administer orlistat at least 3 hours before or after oral cyclosporine. Monitor for decreased serum concentrations of oral cyclosporine, even with the recommended dose separation. Risk D: Consider therapy modification
Levothyroxine: Orlistat may decrease the serum concentration of Levothyroxine. Management: Separate administration of oral levothyroxine and orlistat by a least 4 hours. Monitor patients closely for signs and symptoms of hypothyroidism. Risk D: Consider therapy modification
Paricalcitol: Orlistat may decrease the serum concentration of Paricalcitol. Management: Monitor clinical response to paricalcitol closely when used with orlistat. When this combination must be used, consider administering paricalcitol at least 2 hours before or after the administration of orlistat. Risk D: Consider therapy modification
Propafenone: Orlistat may decrease the serum concentration of Propafenone. Risk C: Monitor therapy
Vitamin D Analogs: Orlistat may decrease the serum concentration of Vitamin D Analogs. More specifically, orlistat may impair absorption of Vitamin D Analogs. Management: Monitor clinical response (including serum calcium) to oral vitamin D analogs closely if used with orlistat. If this combination must be used, consider giving the vitamin D analog at least 2 hrs before or after orlistat. Exceptions: Calcipotriene. Risk D: Consider therapy modification
Vitamins (Fat Soluble): Orlistat may decrease the serum concentration of Vitamins (Fat Soluble). Management: Administer oral fat soluble vitamins at least 2 hours before or after the administration of orlistat. Similar precautions do not apply to parenterally administered fat soluble vitamins. Risk D: Consider therapy modification
Warfarin: Orlistat may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Fat-soluble vitamins: Absorption of vitamins A, D, E, and K may be decreased by orlistat. A multivitamin containing the fat-soluble vitamins (A, D, E, and K) should be administered once daily at least 2 hours before or after orlistat.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
A reversible inhibitor of gastric and pancreatic lipases, thus inhibiting absorption of dietary fats by 30% (at doses of 120 mg 3 times/day).
Pharmacodynamics/Kinetics
Onset of action: 24-48 hours
Duration: 48-72 hours
Absorption: Minimal
Protein binding: >99% (lipoproteins and albumin)
Metabolism: Metabolized within the gastrointestinal wall; forms inactive metabolites
Half-life elimination: 1-2 hours
Time to peak, serum: ~8 hours
Excretion: Feces (~97%, 83% as unchanged drug); urine (<2%)
Dosage
Oral:
Children ≥12 years and Adults (Xenical®): 120 mg 3 times/day with each main meal containing fat (during or up to 1 hour after the meal); omit dose if meal is occasionally missed or contains no fat.
Adults (Alli™): OTC labeling: 60 mg 3 times/day with each main meal containing fat
Administration: Oral
Administer during or up to 1 hour after each main meal containing fat.
Monitoring Parameters
BMI; diet (calorie and fat intake); serum glucose in patients with diabetes; thyroid function in patient with thyroid disease; liver function tests in patients exhibiting symptoms of hepatic dysfunction
Dietary Considerations
Multivitamin supplements that contain fat-soluble vitamins should be taken once daily at least 2 hours before or after the administration of orlistat (ie, bedtime). Gastrointestinal effects of orlistat may increase if taken with any one meal very high in fat. Distribute daily intake of carbohydrates, fat (~30% of daily calories), and protein over three main meals.
Patient Education
Maintain prescribed diet (ideally a low-fat diet; high-fat meals may result in GI distress), exercise regimen, and vitamin supplements as prescribed. You may experience dizziness, lightheadedness, or increased flatus and fecal urgency (this may lessen with continued use). Report persistent back, muscle, or joint pain; signs of respiratory tract infection or flu-like symptoms; skin rash or irritation; severe fatigue; fever; yellowing of skin or eyes; brown urine; abdominal pain; or persistent nausea or vomiting.
Cardiovascular Considerations
Obesity is a modifiable risk factor for cardiovascular disease. When combined with dietary measures, orlistat may decrease weight by 3-4 kg. Orlistat and dietary measures resulted in a greater reduction in the incidence of type 2 diabetes mellitus (noninsulin dependent, NIDDM) over 4 years in obese patients with impaired glucose tolerance (Torgerson, 2004).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause anxiety, fatigue, and sleep disorders
Mental Health: Effects on Psychiatric Treatment
None reported; be vigilant for abuse in patients with anorexia nervosa or bulimia
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral:
Alli®: 60 mg
Xenical®: 120 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Alli)
60 mg (60): $45.99
Capsules (Xenical)
120 mg (10): $53.99
References
American Dietetic Association; American Society of Nutrition, Siega-Riz AM, et al, "Position of the American Dietetic Association and American Society for Nutrition: Obesity, Reproduction, and Pregnancy Outcomes," J Am Diet Assoc, 2009, 109(5):918-27.
August GP, Caprio S, Fennoy I, et al, “Prevention and Treatment of Pediatric Obesity: An Endocrine Society Clinical Practice Guideline Based on Expert Opinion,” J Clin Endocrinol Metab, 2008, 93(12):4576-99.
Davidson MH, Hauptman J, DiGirolamo M, et al, “Weight Control and Risk Factor Reduction in Obese Subjects Treated for 2 Years With Orlistat: A Randomized Controlled Trial,” JAMA, 1999, 281(3):235-42.
Heymsfield SB, Segal KR, Hauptman J, et al, “Effects of Weight Loss With Orlistat on Glucose Tolerance and Progression to Type 2 Diabetes in Obese Adults,” Arch Intern Med, 2000, 160(9):1321-6.
Hollander PA, Elbein SC, Hirsch IB, et al, “Role of Orlistat in the Treatment of Obese Patients With Type 2 Diabetes. A 1-year Randomized Double-Blind Study,” Diabetes Care, 1998, 21(8):1288-94.
IOM (Institute of Medicine) and NRC (National Research Council), "Weight Gain During Pregnancy: Reexamining the Guidelines," Washington, DC: The National Academies Press, 2009. Available at http://www.nap.edu
McTigue KM, Harris R, Hemphill B, et al, “Screening and Interventions for Obesity in Adults: Summary of the Evidence for the U.S. Preventive Services Task Force,” Ann Intern Med, 2003, 139(11):933-49.
National Heart, Lung, and Blood Institute Obesity Education Initiative, “Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. The Evidence Report,” NIH Publication No. 98-4083. Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, 1998.
Snow V, Barry P, Fitterman N, et al, “Pharmacologic and Surgical Management of Obesity in Primary Care: A Clinical Practice Guideline From the American College of Physicians,” Ann Intern Med, 2005, 142(7):525-31.
Torgenson JS, Pauptman J, Boldrin MN, et al, “XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study: A Randomized Study of Orlistat as an Adjunct to Lifestyle Changes for the Prevention of Type 2 Diabetes in Obese Patients,” Diabetes Care, 2004, 27(1):155-61.
Weir MA, Beyea MM, Gomes T, et al, "Orlistat and Acute Kidney Injury: An Analysis of 953 Patients," Arch Intern Med, 2011, 171(7):703-4.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
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