orlistat
Xenical

Available forms
Available by prescription only
Capsules: 120 mg

Indications and dosages
 Management of obesity, including weight loss and weight maintenance with a reduced-calorie diet; reduction of risk of weight regain after weight loss. Adults: 120 mg P.O. t.i.d. with each main meal that contains fat (during or up to 1 hour after the meal).

Pharmacodynamics
Antiobesity action: As a reversible inhibitor of lipases, orlistat forms a bond with the active site of gastric and pancreatic lipases. These inactivated enzymes are unavailable to hydrolyze dietary fat, in the form of triglycerides, into absorbable free fatty acids and monoglycerides. Because the undigested triglycerides aren’t absorbed, the resulting caloric deficit may have a positive effect on weight control. The recommended dose of 120 mg t.i.d. inhibits dietary fat absorption by about 30%.

Pharmacokinetics
Absorption: Systemic exposure to orlistat is minimal because only a small amount of the drug is absorbed.
Distribution: More than 99% binds to plasma proteins; lipoproteins and albumin are major binding proteins.
Metabolism: Primarily metabolized within the GI wall.
Excretion: Most of unabsorbed drug is excreted in feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to orlistat or its components and in patients with chronic malabsorption syndrome or cholestasis. Also, exclude organic causes of obesity such as hypothyroidism before starting orlistat therapy.
 Use cautiously in patients with a risk of anorexia nervosa or bulimia or a history of hyperoxaluria or calcium oxalate nephrolithiasis. Use cautiously in patients receiving cyclosporine because of potential changes in cyclosporine absorption related to variations in dietary intake.

Interactions
Drug-drug. Cyclosporine: May alter cyclosporine absorption related to variations in dietary intake. Monitor cyclosporine levels if used together.
Fat-soluble vitamins such as vitamin E and beta-carotene: May decrease absorption of these drugs. Separate administration times by 2 hours.
Pravastatin: Increases pravastatin levels and causes additive lipid-lowering effect. Monitor patient.
Warfarin: May alter coagulation parameters. Monitor PT and INR.

Adverse reactions
CNS: headache, dizziness, fatigue, sleep disorder, anxiety, depression.
CV: pedal edema.
EENT: otitis.
GI: oily spotting, flatus with discharge, fecal urgency, fatty or oily stool, oily evacuation, increased defecation, abdominal pain, fecal incontinence, nausea, infectious diarrhea, rectal pain, vomiting, tooth and gingival disorders.
GU: menstrual irregularity, vaginitis, urinary tract infection.
Musculoskeletal: back pain, pain in legs, arthritis, myalgia, joint disorder, tendonitis.
Respiratory: flu syndrome, upper respiratory tract infection, lower respiratory tract infection.
Skin: rash, dry skin.

Effects on lab test results
None reported.

Overdose and treatment
If an overdose occurs, stop drug and observe patient for 24 hours. Systemic effects attributable to lipase inhibition should reverse rapidly.

Special considerations
• Drug is recommended for patients with an initial body mass index of 30 kg/m² or more, or 27 kg/m² or more if patient has other risk factors, such as hypertension, diabetes, or dyslipidemia.
• Patient should adhere to dietary guidelines. GI effects may increase when patient takes orlistat with high-fat foods-specifically, when more than 30% of total daily calories come from fat.
• Orlistat reduces absorption of some fat-soluble vitamins and beta-carotene. Patient may need a multivitamin supplement that contains fat-soluble vitamins during orlistat therapy.
• In diabetic patients, improved metabolic control may accompany weight loss, so the dosage of oral antidiabetic or insulin may need to be reduced. Monitor serum glucose.
• It’s unknown if orlistat is safe and effective when therapy lasts longer than 2 years.
• As with any weight loss agent, the risk of misuse exists in certain patient populations, such as patients with anorexia nervosa or bulimia.
Pregnant patients
• Effects on fetus aren’t known. Drug isn’t recommended for use in pregnant women.
Breast-feeding patients
• It isn’t known if orlistat appears in breast milk. Avoid use in breast-feeding women.
Pediatric patients
• Safety and efficacy haven’t been established.
Geriatric patients
• It isn’t known if elderly patients respond differently to the drug than younger patients.

Patient education
• Advise patient to follow a nutritionally balanced, reduced-calorie diet that derives only 30% of its calories from fat. The daily intake of fat, carbohydrate, and protein should be distributed over three main meals. If a meal is occasionally missed or contains no fat, patient can omit a dose.
• To ensure adequate nutrition, advise patient to take a daily multivitamin supplement that contains fat-soluble vitamins at least 2 hours before or after orlistat, such as at bedtime.
• Tell patient with diabetes that weight loss may improve glycemic control, so oral antidiabetic (such as a sulfonylurea or metformin) or insulin dosage may be reduced during orlistat therapy.
• Tell women to call if pregnancy or breast-feeding is planned.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use