Xenical (Orlistat)

XENICAL is indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet. XENICAL is also indicated to reduce the risk for weight regain after prior weight loss. XENICAL is indicated for obese patients with an initial body mass index (BMI) ≥30 kg/m


² or ≥27 kg/m


² in the presence of other risk factors (e.g., hypertension, diabetes, dyslipidemia).

Table 1 Body Mass Index (BMI), kg/m²Conversion Factors: Weight in lbs ÷ 2.2 = weight in kilograms (kg) Height in inches × 0.0254 = height in meters (m) 1 foot = 12 inches

Table 1 Body Mass Index (BMI), kg/m



²Conversion Factors: Weight in lbs ÷ 2.2 = weight in kilograms (kg) Height in inches × 0.0254 = height in meters (m) 1 foot = 12 inches

• One 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal). (
  
  2 DOSAGE AND ADMINISTRATION

  • One 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).
  • Advise patients to take a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat.
  • Distribute the daily intake of fat, carbohydrate, and protein over three main meals.
  • Advise patients to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition.
  • Take the vitamin supplement at least 2 hours before or after the administration of XENICAL, such as at bedtime.
  • For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.
  • For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart.

  2.1 Recommended Dosing

  The recommended dose of XENICAL is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

  The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of 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, the dose of XENICAL can be omitted.

  Because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition

  [see Warnings and Precautions (5.1)]

  . The vitamin supplement should be taken at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.

  For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function.

  Doses above 120 mg three times a day have not been shown to provide additional benefit.

  Based on fecal fat measurements, the effect of XENICAL is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.
  )
  
• Advise patients to take a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat. (
  
  2 DOSAGE AND ADMINISTRATION

  • One 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).
  • Advise patients to take a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat.
  • Distribute the daily intake of fat, carbohydrate, and protein over three main meals.
  • Advise patients to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition.
  • Take the vitamin supplement at least 2 hours before or after the administration of XENICAL, such as at bedtime.
  • For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.
  • For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart.

  2.1 Recommended Dosing

  The recommended dose of XENICAL is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

  The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of 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, the dose of XENICAL can be omitted.

  Because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition

  [see Warnings and Precautions (5.1)]

  . The vitamin supplement should be taken at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.

  For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function.

  Doses above 120 mg three times a day have not been shown to provide additional benefit.

  Based on fecal fat measurements, the effect of XENICAL is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.
  )
  
• Distribute the daily intake of fat, carbohydrate, and protein over three main meals. (
  
  2 DOSAGE AND ADMINISTRATION

  • One 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).
  • Advise patients to take a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat.
  • Distribute the daily intake of fat, carbohydrate, and protein over three main meals.
  • Advise patients to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition.
  • Take the vitamin supplement at least 2 hours before or after the administration of XENICAL, such as at bedtime.
  • For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.
  • For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart.

  2.1 Recommended Dosing

  The recommended dose of XENICAL is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

  The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of 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, the dose of XENICAL can be omitted.

  Because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition

  [see Warnings and Precautions (5.1)]

  . The vitamin supplement should be taken at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.

  For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function.

  Doses above 120 mg three times a day have not been shown to provide additional benefit.

  Based on fecal fat measurements, the effect of XENICAL is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.
  )
  
• Advise patients to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition. (
  
  2 DOSAGE AND ADMINISTRATION

  • One 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).
  • Advise patients to take a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat.
  • Distribute the daily intake of fat, carbohydrate, and protein over three main meals.
  • Advise patients to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition.
  • Take the vitamin supplement at least 2 hours before or after the administration of XENICAL, such as at bedtime.
  • For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.
  • For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart.

  2.1 Recommended Dosing

  The recommended dose of XENICAL is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

  The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of 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, the dose of XENICAL can be omitted.

  Because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition

  [see Warnings and Precautions (5.1)]

  . The vitamin supplement should be taken at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.

  For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function.

  Doses above 120 mg three times a day have not been shown to provide additional benefit.

  Based on fecal fat measurements, the effect of XENICAL is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.
  )
  
• Take the vitamin supplement at least 2 hours before or after the administration of XENICAL, such as at bedtime. (
  
  2 DOSAGE AND ADMINISTRATION

  • One 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).
  • Advise patients to take a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat.
  • Distribute the daily intake of fat, carbohydrate, and protein over three main meals.
  • Advise patients to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition.
  • Take the vitamin supplement at least 2 hours before or after the administration of XENICAL, such as at bedtime.
  • For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.
  • For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart.

  2.1 Recommended Dosing

  The recommended dose of XENICAL is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

  The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of 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, the dose of XENICAL can be omitted.

  Because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition

  [see Warnings and Precautions (5.1)]

  . The vitamin supplement should be taken at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.

  For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function.

  Doses above 120 mg three times a day have not been shown to provide additional benefit.

  Based on fecal fat measurements, the effect of XENICAL is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.
  )
  
• For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL. (
  
  2 DOSAGE AND ADMINISTRATION

  • One 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).
  • Advise patients to take a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat.
  • Distribute the daily intake of fat, carbohydrate, and protein over three main meals.
  • Advise patients to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition.
  • Take the vitamin supplement at least 2 hours before or after the administration of XENICAL, such as at bedtime.
  • For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.
  • For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart.

  2.1 Recommended Dosing

  The recommended dose of XENICAL is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

  The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of 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, the dose of XENICAL can be omitted.

  Because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition

  [see Warnings and Precautions (5.1)]

  . The vitamin supplement should be taken at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.

  For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function.

  Doses above 120 mg three times a day have not been shown to provide additional benefit.

  Based on fecal fat measurements, the effect of XENICAL is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.
  )
  
• For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart. (
  
  2 DOSAGE AND ADMINISTRATION

  • One 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).
  • Advise patients to take a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat.
  • Distribute the daily intake of fat, carbohydrate, and protein over three main meals.
  • Advise patients to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition.
  • Take the vitamin supplement at least 2 hours before or after the administration of XENICAL, such as at bedtime.
  • For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.
  • For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart.

  2.1 Recommended Dosing

  The recommended dose of XENICAL is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

  The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of 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, the dose of XENICAL can be omitted.

  Because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition

  [see Warnings and Precautions (5.1)]

  . The vitamin supplement should be taken at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  For patients receiving both XENICAL and cyclosporine therapy, administer cyclosporine 3 hours after XENICAL.

  For patients receiving both XENICAL and levothyroxine therapy, administer levothyroxine and XENICAL at least 4 hours apart. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function.

  Doses above 120 mg three times a day have not been shown to provide additional benefit.

  Based on fecal fat measurements, the effect of XENICAL is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.
  )
  

XENICAL 120 mg turquoise capsules imprinted with XENICAL 120 in black ink.

• Nursing Mothers: Caution should be exercised when administered to a nursing woman. (
  
  
  
  
  8.3 Nursing Mothers

  It is not known if XENICAL is present in human milk. Caution should be exercised when XENICAL is administered to a nursing woman.
  )
  
  
  

• XENICAL has drug interactions and can decrease vitamin absorption. (
  5.1 Drug Interactions and Decreased Vitamin Absorption

  XENICAL may interact with concomitant drugs including cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs, and antiretroviral drugs

  [see Drug Interactions (7)].

  Data from a XENICAL and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when XENICAL was coadministered with cyclosporine. Therefore, XENICAL and cyclosporine should not be simultaneously coadministered. To reduce the chance of a drug-drug interaction, cyclosporine should be taken at least 3 hours before or after XENICAL in patients taking both drugs. In addition, in those patients whose cyclosporine levels are being measured, more frequent monitoring should be considered.

  Patients should be strongly encouraged to take a multivitamin supplement that contains fat-soluble vitamins to ensure adequate nutrition because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene

  [see Dosage and Administration (2), and Adverse Reactions (6.1)]

  . In addition, the levels of vitamin D and beta-carotene may be low in obese patients compared with non-obese subjects. The supplement should be taken once a day at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  Weight-loss may affect glycemic control in patients with diabetes mellitus. A reduction in dose of oral hypoglycemic medication (e.g., sulfonylureas) or insulin may be required in some patients

  [see Clinical Studies (14)]

  .
  ,
  7 DRUG INTERACTIONS

  • Cyclosporine:
    Reduction in cyclosporine plasma levels was observed when XENICAL was coadministered with cyclosporine.
  • Fat-soluble Vitamin Supplements and Analogues:
    All patients should take a daily multivitamin that contains vitamins A, D, E, K, and beta-carotene.
  • Levothyroxine:
    Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function.
  • Warfarin:
    Patients on chronic stable doses of warfarin who are prescribed XENICAL should be monitored closely for changes in coagulation parameters.
  • Amiodarone:
    A reduction in exposure to amiodarone was observed when XENICAL was co-administered.
  • Antiepileptic Drugs:
    Convulsions have been reported in patients taking XENICAL with antiepileptic drugs. Patients should be monitored for possible changes in frequency or severity of convulsions.
  • Antiretroviral Drugs:
    Loss of virological control has been reported in HIV-infected patients. Patients should be monitored frequently for changes in HIV RNA levels.

  7.1 Cyclosporine

  Data from a XENICAL and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when XENICAL was coadministered with cyclosporine. XENICAL and cyclosporine should not be simultaneously coadministered. Cyclosporine should be administered 3 hours after the administration of XENICAL

  [see Dosage and Administration (2), and Warnings and Precautions (5.1)]

  .

  7.2 Fat-soluble Vitamin Supplements and Analogues

  Data from a pharmacokinetic interaction study showed that the absorption of beta-carotene supplement is reduced when concomitantly administered with XENICAL. XENICAL inhibited absorption of a vitamin E acetate supplement. The effect of XENICAL on the absorption of supplemental vitamin D, vitamin A, and nutritionally-derived vitamin K is not known at this time

  [see Clinical Pharmacology (12.3), and Warnings and Precautions (5.1)]

  .

  7.3 Levothyroxine

  Hypothyroidism has been reported in patients treated concomitantly with XENICAL and levothyroxine postmarketing. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function. Administer levothyroxine and XENICAL at least 4 hours apart

  [see Dosage and Administration (2)]

  .

  7.4 Anticoagulants including Warfarin

  Vitamin K absorption may be decreased with XENICAL. Reports of decreased prothrombin, increased INR and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with XENICAL and anticoagulants. Patients on chronic stable doses of warfarin or other anticoagulants who are prescribed XENICAL should be monitored closely for changes in coagulation parameters

  [see Clinical Pharmacology (12.3)]

  .

  7.5 Amiodarone

  A pharmacokinetic study, where amiodarone was orally administered during orlistat treatment, demonstrated a reduction in exposure to amiodarone and its metabolite, desethylamiodarone

  [see Clinical Pharmocology (12.3)]

  . A reduced therapeutic effect of amiodarone is possible. The effect of commencing orlistat treatment in patients on stable amiodarone therapy has not been studied.

  7.6 Antiepileptic Drugs

  Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic drugs. Patients should be monitored for possible changes in the frequency and/or severity of convulsions.

  7.7 Antiretroviral Drugs

  Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs such as atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, and with the combinations lopinavir/ritonavir and emtricitabine/efavirenz/tenofovir disoproxil fumarate. The exact mechanism for this is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. HIV RNA levels should be frequently monitored in patients who take XENICAL while being treated for HIV infection. If there is a confirmed increase in HIV viral load, XENICAL should be discontinued.
  )
• Take a multivitamin supplement that contains fat-soluble vitamins to ensure adequate nutrition. (
  5.1 Drug Interactions and Decreased Vitamin Absorption

  XENICAL may interact with concomitant drugs including cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs, and antiretroviral drugs

  [see Drug Interactions (7)].

  Data from a XENICAL and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when XENICAL was coadministered with cyclosporine. Therefore, XENICAL and cyclosporine should not be simultaneously coadministered. To reduce the chance of a drug-drug interaction, cyclosporine should be taken at least 3 hours before or after XENICAL in patients taking both drugs. In addition, in those patients whose cyclosporine levels are being measured, more frequent monitoring should be considered.

  Patients should be strongly encouraged to take a multivitamin supplement that contains fat-soluble vitamins to ensure adequate nutrition because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene

  [see Dosage and Administration (2), and Adverse Reactions (6.1)]

  . In addition, the levels of vitamin D and beta-carotene may be low in obese patients compared with non-obese subjects. The supplement should be taken once a day at least 2 hours before or after the administration of XENICAL, such as at bedtime.

  Weight-loss may affect glycemic control in patients with diabetes mellitus. A reduction in dose of oral hypoglycemic medication (e.g., sulfonylureas) or insulin may be required in some patients

  [see Clinical Studies (14)]

  .
  )
• Rare cases of severe liver injury with hepatocellular necrosis or acute hepatic failure have been reported. (
  5.2 Liver Injury

  There have been rare postmarketing reports of severe liver injury with hepatocellular necrosis or acute hepatic failure in patients treated with XENICAL, with some of these cases resulting in liver transplant or death. Patients should be instructed to report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, dark urine, light-colored stools, or right upper quadrant pain) while taking XENICAL. When these symptoms occur, XENICAL and other suspect medications should be discontinued immediately and liver function tests and ALT and AST levels obtained.
  )
• Patients may develop oxalate nephrolithiasis and oxalate nephropathy following treatment with XENICAL. Monitor renal function in patients at risk for renal insufficiency. Discontinue XENICAL if oxalate nephropathy develops. (
  5.3 Oxalate Nephrolithiasis and Oxalate Nephropathy with Renal Failure

  Some patients may develop increased levels of urinary oxalate following treatment with XENICAL. Cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure have been reported. Monitor renal function when prescribing XENICAL to patients at increased risk for oxalate nephropathy, including patients with renal impairment and in those with a history of hyperoxaluria or calcium oxalate nephrolithiasis. Discontinue XENICAL in patients who develop oxalate nephropathy.
  )
• Substantial weight loss can increase the risk of cholelithiasis. (
  5.4 Cholelithiasis

  Substantial weight loss can increase the risk of cholelithiasis. In a clinical trial of XENICAL for the prevention of type 2 diabetes, the rates of cholelithiasis as an adverse event were 2.9% (47/1649) for patients randomized to XENICAL and 1.8% (30/1655) for patients randomized to placebo.
  )
• Exclude organic causes of obesity (eg, hypothyroidism) before prescribing XENICAL. (
  5.5 Miscellaneous

  Organic causes of obesity (e.g., hypothyroidism) should be excluded before prescribing XENICAL.

  Patients should be advised to adhere to dietary guidelines

  [see Dosage and Administration (2)]

  . Gastrointestinal events

  [see Adverse Reactions (6.1)]

  may increase when XENICAL is taken with a diet high in fat (>30% total daily calories from fat). The daily intake of fat should be distributed over three main meals. If XENICAL is taken with any one meal very high in fat, the possibility of gastrointestinal effects increases.
  )
• Gastrointestinal events may increase when XENICAL is taken with a diet high in fat (>30% total daily calories from fat). (
  5.5 Miscellaneous

  Organic causes of obesity (e.g., hypothyroidism) should be excluded before prescribing XENICAL.

  Patients should be advised to adhere to dietary guidelines

  [see Dosage and Administration (2)]

  . Gastrointestinal events

  [see Adverse Reactions (6.1)]

  may increase when XENICAL is taken with a diet high in fat (>30% total daily calories from fat). The daily intake of fat should be distributed over three main meals. If XENICAL is taken with any one meal very high in fat, the possibility of gastrointestinal effects increases.
  )