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Product Information

  • Indications

  • Efficacy

  • Contraindications and Warnings

  • Precautions

  • Adverse Events

  • Dosage and Administration


    Indications

    XENICAL acts locally to inhibit GI lipases, blocking the absorption of approximately 30% of dietary fat. 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 of weight regain after prior weight loss. XENICAL is indicated for obese patients with an initial BMI of >30 kg/m2 or >27 kg/m2 in the presence of other risk factors, such as type 2 diabetes, hypertension and dyslipidemia.

    How XENICAL Works
    How XENICAL Works

    How fat blocking works
    • XENICAL acts locally to inhibit the fat-digesting action of lipases in the GI tract.
    • Intact triglycerides pass through the intestines unabsorbed, creating a caloric deficit.
    • Absorption of carbohydrates and proteins is not affected, which may have a positive effect on weight control.


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    Efficacy

    In clinical trials, XENICAL plus diet:
    • Provided twice the mean weight loss as placebo plus diet
    • Maintained mean weight loss better than placebo plus diet20,57
    • Improved cardiovascular and metabolic risk factors better than placebo plus diet20,28,57
    XENICAL was evaluated in the 4-year XENDOS study and in 7 long-term studies (1 to 2 years' duration) involving more than 4000 patients. XENICAL has proven safety and tolerability profiles.

    Year 1: Faster and greater weight loss 57

    Year 1: Faster and greater weight loss

    In one study, 3 times as many patients (25% on XENICAL plus diet versus 8% on placebo plus diet, P<0.001) lost >10% of their body weight from randomization (mean: 31 lbs;
    range: 18 to 67lbs).18

    In 5 studies:
    • Two to 5 times as many patients on XENICAL plus diet lost >10% of their body weight from randomization versus those on placebo plus diet.
    • Pooled data showed overall mean weight loss from randomization was 13.4 lbs for XENICAL plus diet versus 5.8 lbs for placebo plus diet.
    Year 2: Significant weight loss maintained

    Year 2: Percentage of patients losing >=10% and >=5% of body weight from randomization

    In one study, almost 4 times as many patients on XENICAL plus diet maintained a weight loss of >10% of their body weight from randomization versus those on placebo plus diet.

    In 4 studies:
    • Two to 5 times as many patients on XENICAL plus diet maintained a weight loss of >10% of their body weight from randomization versus those on placebo plus diet.

    Dyslipidemia

    Sustained weight loss with improvement in cardiovascular risk factors

    LDL cholesterol: patients with LDL of >130 mg/dL at randomization
    • At year 1, XENICAL plus diet was more effective in reducing LDL cholesterol than placebo plus diet for any weight-loss category.
    Year 1: Mean change in LDL cholesterol in patients with LDL cholesterol >=130 mg/dL
    • At year 1, the mean change from randomization in LDL cholesterol was -7.8% for XENICAL plus diet versus +1.1% for placebo plus diet (P<0.001).15
    • For XENICAL plus diet, there was a consistent decline in LDL cholesterol for 12 weeks following randomization, an improvement that was maintained through week 52.
    • In contrast, for placebo plus diet, mean LDL cholesterol levels generally remained close to levels at randomization.
    • At year 2, the improvements seen with XENICAL plus diet were maintained (P<0.001).
    In the population as a whole, including patients with normal LDL at randomization:
    • The mean change in LDL cholesterol at year 1 was -4.0% for XENICAL plus diet and +5.0% for placebo plus diet (P<0.001).
    The long-term effects of orlistat on morbidity and mortality associated with obesity have not been established.

    Hypertension

    XENICAL plus diet improved both systolic and diastolic blood pressures versus placebo plus diet.

    Year 1: Mean change from randomization in patients with abnormal blood pressure

    The long-term effects of orlistat on morbidity and mortality associated with obesity have not been established.

    Type 2 Diabetes

    Efficacy and safety demonstrated in a 1-year study of obese type 2 diabetics on sulfonylureas (n=321) 28

    Improved Glycemic Control -Year 1: Mean changes from randomization in sulfonylurea usage in type 2 diabetes patients

    Significantly more patients on XENICAL plus diet reduced or discontinued sulfonylurea usage versus those on placebo plus diet (43.2% vs. 28.9%, P<0.05), with significantly greater reductions in mean dosage (P<0.05).

    Decrease in HbA1c in patients with HbA1c greater than 8%

    Delay in onset of type 2 diabetes and treatment with XENICAL - XENDOS study

    In the 4-year XENDOS study, the effects of orlistat on weight loss and in delaying the onset of type 2 diabetes was compared to placebo in 3304 obese patients who had either normal or impaired glucose tolerance at baseline. At the end of the 1st year of treatment, 73% of the XENICAL treated patients and 45% of the placebo treated patients had a >5% weight loss. After 4 years, the relative risk reduction for developing type 2 diabetes in patients with impaired glucose tolerance was 42% less in the diet plus XENICAL group compared to the diet plus placebo group (p<0.01). In addition, greater reductions in total cholesterol, LDL-cholesterol, LDL/HDL ratio, fasting insulin systolic and diastolic blood pressure and waist circumference were observed in diet plus XENICAL treated patients compared to diet plus placebo treated patients.

    The long-term effects of XENICAL (orlistat) on morbidity and mortality associated with obesity have not been established.

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    Contraindications and Warnings
    • XENICAL is contraindicated in patients with chronic malabsorption syndrome or cholestasis (impaired bile flow), and in patients with known hypersensitivity to XENICAL or to any component of this product.
    • Organic causes of obesity, such as hypothyroidism, should be excluded before prescribing XENICAL.
    • To reduce the chance of drug-drug interaction resulting in reduced levels of cyclosporine, XENICAL and cyclosporine should not be taken within 2 hours of each other. More frequent monitoring of cyclosporine levels should be considered in patients taking both drugs.

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    Precautions

    Fat-Soluble Vitamins

    When taking XENICAL, patients should be advised to take a multivitamin supplement containing fat-soluble vitamins to ensure adequate nutrition, because XENICAL has been shown to reduce the absorption of some fat-soluble vitamins, including beta-carotene, and because the status of obese patients in general and patients on weight-control diets may be low. The supplement should be taken once a day at least 2 hours before or after administration of XENICAL, such as bedtime.

    Toxicology

    No detectable mutagenic or genotoxic activity as determined by the Ames test, mammalian forward mutation assay, in vitro clastogenesis assay, an unscheduled DNA synthesis assay, and in vivo mouse micronucleus test. Did not show carcinogenic potential at doses of 38x and 46x the daily human dose.

    Inappropriate Use

    As with any weight-loss agent, the potential exists for misuse of XENICAL in inappropriate patient populations (eg, patients with anorexia nervosa or bulimia). See recommended prescribing guidelines for more detail.

    Pregnancy Category B
    Animal reproductive studies are not always predictive of human response.

    XENICAL is not recommended for use during pregnancy.

    Nursing Mothers

    It is not known if XENICAL is secreted in human milk, and XENICAL should not be taken by nursing mothers.

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    Adverse Events

    Gastrointestinal symptoms are the most commonly observed (incidence of 5% or more, and twice that of placebo) adverse events associated with the use of XENICAL in the double-blind, placebo-controlled clinical trials, and are primarily a manifestation of the mechanism of action. The most common of these adverse events were oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation and fecal incontinence.

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    Dosage and Administration
    • The recommended dose of XENICAL is one 120-mg capsule 3 times a day, once 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 3 main meals. If a meal is occasionally missed or contains no fat, the dose of XENICAL can be omitted.
    • Doses above 120 mg 3 times a day have not been shown to provide additional benefit.
    • The safety and effectiveness of XENICAL beyond 4 years have not been determined at this time.

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    Mechanism of Action

    Physicians' FAQ

    Managing Patients with Obesity-Related Comorbidities

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    References | Roche in Obesity

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