Administration

Pharmacologic Category

Lipase Inhibitor

Dosing: Adult

Obesity: Oral:

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.

Alli™: OTC labeling: 60 mg 3 times/day with each main meal containing fat

Dosing: Pediatric

Obesity (Xenical®): Children ≥12 years: Refer to adult dosing.

Dosing: Geriatric

Refer to adult dosing

Administer during or up to 1 hour after each main meal containing fat.

Use;

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)

Adverse Reactions Significant

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%), gingival disorder (2% to 4%), tooth disorder (3% 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% (Limited to important or life-threatening): 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), hepatic failure, hepatitis (causal relationship not established), hypersensitivity, hypoglycemia (in patients with diabetes), hypothyroidism (concurrent use with levothyroxine), kidney injury (acute), pancreatitis, pruritus, rash, transaminases increased, urinary oxalate levels increased, urticaria

Contraindications

Hypersensitivity to orlistat or any component of the formulation; chronic malabsorption syndrome or cholestasis

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; 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.

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.

• Long-term therapy: Safety and efficacy have not been established with use >4 years.

• 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.

Drug Interactions

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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 2 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 2 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

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.

Pregnancy Risk Factor

B (show table)

Pregnancy Implications

Teratogenic effects or embryotoxicity were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, orlistat is not recommended for use during pregnancy.

Lactation

Excretion in breast milk unknown/not recommended

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.