Orlistat (XENICAL)

1. Health Canada Product Monograph — Orlistat

• Orlistat, combined with a mildly hypocaloric diet, is used for weight loss and weight maintenance in obese adults with a body mass index (BMI) of 30 kg/m² or higher, or 27 kg/m² or higher with other risk factors such as hypertension, type 2 diabetes, or high cholesterol.
• Orlistat is used to help reduce the risk of regaining weight after prior weight loss.
• Orlistat can be added to sulfonylureas, metformin, or insulin therapy to improve blood glucose control in overweight or obese patients with type 2 diabetes who remain inadequately controlled on diet and exercise alone.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Orlistat is contraindicated during pregnancy, since weight loss offers no benefit to a pregnant woman and may cause fetal harm.
• Animal studies did not show teratogenicity or embryotoxicity, but animal data are not always predictive of the human response, and no adequate human studies exist.

• Orlistat is contraindicated while breastfeeding.
• It is not known whether orlistat passes into human breast milk.

• No dose adjustment is needed for older adults.
• Clinical studies did not include enough patients aged 65 and older to determine whether they respond differently than younger adults.

• Orlistat is not authorized for use in children under 12 years of age, since no data are available to Health Canada for this age group.
• In adolescents aged 12 to 16 years, the side-effect profile was generally similar to that seen in adults.

• The recommended dose is one 120 mg capsule three times daily, taken during or up to 1 hour after each main meal.
• If a meal is occasionally skipped or contains no fat, that dose of orlistat can be omitted.
• Doses higher than 120 mg three times daily provide no additional benefit.
• If a dose is missed, it can still be taken up to 1 hour after the last meal, but doses should never be doubled to make up for a missed one.
• A multivitamin containing fat-soluble vitamins should be taken at least 2 hours before or after orlistat, such as at bedtime, since orlistat reduces absorption of some fat-soluble vitamins.
• No dose adjustment has been studied for hepatic or renal impairment, since these populations have not been specifically investigated.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Doses well above the recommended amount have been studied without significant adverse effects.
• Post-marketing overdose reports describe either no adverse effects or effects similar to those seen at the recommended dose.
• Patients should be observed for 24 hours following a significant overdose.
• Any systemic effects from excess fat-absorption blockade are expected to resolve quickly.

• Oily spotting from the rectum may occur.
• Passing gas with oily discharge may occur.
• Fecal urgency may occur.
• Fatty or oily stools may occur.
• Oily bowel evacuation may occur.
• Increased frequency of bowel movements may occur.
• Fecal incontinence may occur.
• Abdominal pain or discomfort may occur.
• Headache may occur.
• Back pain may occur.
• Upper respiratory tract infection may occur.
• Menstrual irregularities may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Rare but serious liver injury, including hepatocellular necrosis or acute liver failure, has been reported, sometimes requiring liver transplant or resulting in death.
• Hypothyroidism, or reduced control of existing hypothyroidism, can occur, particularly in patients also taking levothyroxine.
• Rectal bleeding has been reported and should be investigated if severe or persistent.
• Pancreatitis has been reported.
• Diverticulitis has been reported.
• Hyperoxaluria and oxalate nephropathy with kidney failure have been reported, particularly in patients with a history of kidney stones.
• Hypersensitivity reactions, including itching, rash, hives, swelling, bronchospasm, and anaphylaxis, have been reported rarely.
• Convulsions have been reported in patients taking antiepileptic drugs together with orlistat.
• Changes in blood clotting, including decreased prothrombin and increased INR, have been reported in patients on anticoagulants.
• Rare cases of bullous skin eruptions have been reported.
• Seek urgent medical attention for yellowing of the skin or eyes, dark urine, severe abdominal pain, or signs of a severe allergic reaction.

• Use with caution in patients with pre-existing disease of the large bowel or rectum.
• Use with caution in patients with type 2 diabetes taking insulin or sulfonylureas, since weight loss may require a reduction in their dose to avoid hypoglycemia.
• Use with caution in patients taking levothyroxine, and monitor thyroid function.
• Use with caution in patients taking anticonvulsants, and monitor for changes in seizure frequency or severity.
• Use with caution in patients taking oral anticoagulants, and monitor coagulation parameters such as INR.
• Use with caution in patients taking cyclosporine, and monitor cyclosporine levels more frequently.
• Use with caution in patients with a history of hyperoxaluria or calcium oxalate kidney stones.
• Use with caution in patients with anorexia nervosa or bulimia, given the potential for misuse of a weight-loss agent.
• An additional method of contraception is recommended in case of severe diarrhea, since orlistat may indirectly reduce the effectiveness of oral contraceptives.

• Contraindicated in patients with chronic malabsorption syndrome.
• Contraindicated in patients with cholestasis.
• Contraindicated during pregnancy.
• Contraindicated while breastfeeding.
• Contraindicated in patients with known hypersensitivity to orlistat or to any ingredient in the formulation, including any non-medicinal ingredient or component of the container.

• Cyclosporine levels may be reduced when taken with orlistat, and more frequent monitoring is recommended.
• Absorption of fat-soluble vitamin supplements and beta-carotene may be reduced, so a multivitamin should be taken separately from orlistat.
• Oral anticoagulants such as warfarin may require closer monitoring of coagulation parameters due to possible effects on vitamin K absorption.
• Antiepileptic drugs may be less well absorbed, potentially reducing seizure control.
• Antidepressants, antipsychotics (including lithium), and benzodiazepines may have reduced effectiveness if started around the same time as orlistat.
• Antiretroviral medications for HIV may have reduced absorption and effectiveness.
• Amiodarone exposure may be reduced when co-administered with orlistat, with unclear clinical significance.
• Levothyroxine absorption may be reduced, potentially causing or worsening hypothyroidism.
• Oral contraceptive effectiveness may be indirectly reduced if severe diarrhea occurs; an additional contraceptive method is recommended in this situation.
• Combining orlistat with acarbose should be avoided, since no interaction studies have been conducted.
• No clinically significant interactions were found with digoxin, warfarin pharmacokinetics, phenytoin, glyburide, metformin, nifedipine, atenolol, captopril, furosemide, losartan, fibrates, atorvastatin, or pravastatin.

• No specific food-interaction studies exist, but consuming a diet with more than 30% of calories from fat increases the likelihood and severity of oily, gas-related, and bowel side effects.
• Distributing dietary fat evenly across three main meals rather than concentrating it in one meal helps minimize gastrointestinal side effects.

• Take with, or up to 1 hour after, each main meal that contains fat; the dose can be skipped if a meal is fat-free or missed.

• Store in the original packaging at 15°C to 25°C, protected from light and moisture.
• Keep out of the reach and sight of children.

• Orlistat blocks the absorption of about a third of the fat you eat and is taken together with a reduced-fat diet for weight loss or to help prevent regaining lost weight.
• Take a multivitamin containing fat-soluble vitamins at bedtime or well apart from your orlistat doses, since it can reduce vitamin absorption.
• Oily stools, gas with discharge, and urgent bowel movements are common and related to dietary fat intake; a lower-fat diet reduces these effects.
• Seek prompt medical attention for yellowing skin or eyes, dark urine, or severe abdominal pain, which could indicate liver problems.