Xenical

— THERAPEUTIC DISORDERS TREATED —
  • Obesity
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Xenical Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Orlistat 120mg; caps.

    Pharmacological Class

    Lipase inhibitor.

    How Supplied

    Caps—90

    How Supplied

    Xenical 120mg is a turquoise, hard-gelatin capsule containing pellets of powder. It is imprinted with XENICAL 120 in black ink.

    Xenical is supplied in bottles containing 90 capsules.

    Storage

    Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Keep the bottle tightly closed. Do not use after the given expiration date.

    Manufacturer

    H2 Pharma, LLC

    Generic Availability

    NO

    Xenical Indications

    Indications

    Adjunct to reduced-calorie diet in obesity management, including weight loss and weight maintenance. To reduce risk of weight regain after weight loss. For use in patients with initial body mass index ≥30kg/m2 or ≥27kg/m2 in the presence of other risk factors.

    Xenical Dosage and Administration

    Adult

    Use with a reduced calorie diet with about 30% of calories from fat; spread fat intake over 3 main meals. 120mg three times daily during or up to 1 hour after each of 3 main meals. If a meal is missed or has no fat, skip dose.

    Children

    <12yrs: not established.

    Renal Impairment

    Patients may develop increased levels of urinary oxalate following treatment with Xenical. Monitor renal function in patients at risk for renal insufficiency.

    Xenical Contraindications

    Contraindications

    Pregnancy. Chronic malabsorption syndrome. Cholestasis.

    Xenical Boxed Warnings

    Not Applicable

    Xenical Warnings/Precautions

    Warnings/Precautions

    Exclude organic causes of obesity (eg, hypothyroidism). Weight loss may affect doses needed for antidiabetic drugs (monitor). Monitor for symptoms of hepatic dysfunction; discontinue if occurs and obtain liver function tests. Monitor renal function in patients at increased risk for oxalate nephropathy (including those with renal impairment, history of hyperoxaluria or calcium oxalate nephrolithiasis); discontinue if oxalate nephropathy develops. Nursing mothers.

    Warnings/Precautions

    Exclude organic causes of obesity (eg, hypothyroidism).

    GI Effects

    Gastrointestinal events may increase when Xenical is taken with a diet high in fat (>30% total daily calories from fat). If Xenical is taken with any one meal very high in fat, the possibility of gastrointestinal effects increases.

    Diabetes mellitus

    Weight loss may affect glycemic control in patients with diabetes mellitus; a reduction in dose of oral hypoglycemic medication (eg, sulfonylureas) or insulin may be required in some patients.

    Liver injury

    There have been reports of severe liver injury with hepatocellular necrosis or acute hepatic failure in patients treated with Xenical. Discontinue immediately if symptoms of hepatic dysfunction develop and obtain liver function tests and ALT/AST levels.

    Urinary Oxalate Increases

    Increased levels of urinary oxalate possible following Xenical treatment. Cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure have been reported. Monitor renal function in patients at risk for renal impairment. Use with caution in patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis.

    Cholelithiasis

    Risk of cholelithiasis increased with substantial weight loss.

    Pregnancy Considerations

    Xenical  is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm.If used during pregnancy, or if the patient becomes pregnant while using the drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus.

    Nursing Mother Considerations

    Caution should be exercised when Xenical is administered to a nursing woman as it is unknown whether the drug is present in human milk.

    Pediatric Considerations

    Safety and effectiveness in pediatric patients below the age of 12 have not been established.

    Geriatric Considerations

    Clinical studies of Xenical did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients.

    Renal Impairment Considerations

    Patients may develop increased levels of urinary oxalate following treatment with Xenical. Monitor renal function in patients at risk for renal insufficiency.

    Xenical Pharmacokinetics

    Absorption

    Systemic exposure of orlistat is minimal.

    Distribution

    Orlistat was >99% bound to plasma proteins.

    Elimination

    Fecal excretion of the unabsorbed drug was found to be the major route of elimination. Approximately 97% of the administered radioactivity was excreted in feces; 83% of that was found to be unchanged orlistat.

    Xenical Interactions

    Interactions

    Antagonizes cyclosporine (give dose 3hrs after Xenical). May decrease absorption of fat-soluble vitamins, beta carotene; supplement diet with a fat-soluble containing multivitamin (separate dosing by at least 2hrs). May antagonize amiodarone. Hypothyroidism with levothyroxine; monitor thyroid function and separate dosing by at least 4hrs. Monitor for convulsions with concomitant antiepileptics. Monitor coagulation parameters with anticoagulants (including warfarin). Monitor HIV RNA levels with concomitant antiretrovirals (eg, atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir/ritonavir, emtricitabine/efavirenz/tenofovir disoproxil fumarate).

    Xenical Adverse Reactions

    Adverse Reactions

    GI effects (oily spotting, flatus with discharge, fecal urgency, fatty/oily stools, oily evacuation, increased defecation, fecal incontinence); cholelithiasis; rare: severe liver injury.

    Adverse Reactions

    Most common treatment emergent adverse reactions (≥5% and at least twice that of placebo) include oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation and fecal incontinence.

    In general, the first occurrence of GI events was within 3 months of starting therapy. Overall, approximately 50% of all episodes of GI adverse events associated with Xenical treatment lasted for <1 week, and a majority lasted for no more than 4 weeks. However, GI adverse events may occur in some individuals over a period of 6 months or longer.

    Low vitamin levels: Xenical has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene.

    In clinical trials in obese diabetic patients, hypoglycemia and abdominal distension were also observed.

    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.

    Cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure have been reported.

    Substantial weight loss can increase the risk of cholelithiasis.

    Xenical Clinical Trials

    Clinical Trials

    The effects of Xenical on weight loss, weight maintenance, and weight regain and on a number of comorbidities (eg, type 2 diabetes, lipids, blood pressure) were assessed in the 4-year XENDOS study and in 7 long-term (1- to 2-years duration) multicenter, double-blind, placebo-controlled clinical trials.

    One-Year Results: Weight Loss, Weight Maintenance and Risk Factors

    Pooled data from 5 clinical trials indicated that the overall mean weight loss from randomization to the end of 1 year of treatment in the intent-to-treat population was 13.4 lbs in the patients treated with Xenical and 5.8 lbs in the placebo-treated patients.

    Of the patients who completed 1 year of treatment, 57% of Xenical-treated patients and 31% of the placebo patients lost at least 5% of their baseline body weight.

    One year of therapy with Xenical resulted in relative improvement in several risk factors.

    Three studies evaluated the effects of Xenical compared with placebo in reducing weight regain after a previous weight loss achieved following either diet alone (Study 14302) or prior treatment with Xenical (Study 14119C and Study 14185):

    • Study 14119C: Patients treated with placebo regained 52% of the weight they had previously lost while the patients treated with Xenical regained 26% of the weight they had previously lost (P <.001).
    • Study 14185: Patients treated with placebo regained 63% of the weight they had previously lost while the patients treated with Xenical regained 35% of the weight they had lost (P <.001).
    • Study 14302: Patients treated with placebo regained 53% of the weight they had previously lost while the patients treated with Xenical regained 32% of the weight that they had lost (P <.001).

    Two-Year Results: Long-Term Weight Control and Risk Factors

    The treatment effects of Xenical were examined for 2 years in four of the five 1-year weight management clinical studies.

    Pooled data from 4 clinical studies indicate that the mean weight loss difference between Xenical and placebo treatment groups at year 2 in those patients who completed 1 year of treatment was 3%.

    The relative differences in risk factors between treatment with Xenical and placebo were similar to the results following 1 year of therapy for total cholesterol, LDL-cholesterol, LDL/HDL ratio, triglycerides, fasting glucose, fasting insulin, diastolic blood pressure, waist circumference, and hip circumference. 

    The relative differences between treatment groups for HDL cholesterol and systolic blood pressure were less than that observed in the year 1 results.

    Four-Year Results: Long-Term Weight Control and Risk Factors

    In the 4-year double-blind, placebo-controlled XENDOS study, the effects of Xenical in delaying the onset of type 2 diabetes and on body weight were compared with placebo in 3304 obese patients who had either normal or impaired glucose tolerance at baseline.

    At the end of the study, the mean percent weight loss in the placebo group was -2.75% vs -5.17% in the Xenical group (P <.001).

    After 4 years of treatment, the mean % difference in weight loss between Xenical treated patients and placebo was 2.5%.

    Xenical delayed the onset of type 2 diabetes such that at the end of 4 years the cumulative incidence rate of diabetes was 8.3% for the placebo group compared with 5.5% for the Xenical group (P =.01).

    Patients With Type 2 Diabetes Study

    A 1-year double-blind, placebo-controlled study in type 2 diabetics (N=321) stabilized on sulfonylureas was conducted.

    Thirty percent of patients treated with Xenical achieved at least a 5% or greater reduction in body weight from randomization compared with 13% of the placebo patients (P <.001).

    Glucose Tolerance in Obese Patients

    Two-year studies that included oral glucose tolerance tests (OGTT) were conducted in obese patients not previously diagnosed or treated for type 2 diabetes.

    Following treatment with Xenical, 0.0% and 7.2% of the patients progressed from normal to diabetic and normal to impaired, respectively, compared with 1.9% and 12.6% of the placebo group, respectively.

    At 2 years. among patients with impaired OGTT at randomization, 50% of placebo patients and 71.7% of Xenical patients had a normal OGTT while 7.5% of placebo patients were found to be diabetic and 1.7% of Xenical patients were found to be diabetic after treatment.

    Pediatric Clinical Studies

    The effects of Xenical on body mass index (BMI) and weight loss were assessed in a 54-week multicenter, double-blind, placebo-controlled study in 539 obese adolescents.

    Following 1 year of treatment, BMI decreased by an average of 0.55 kg/m2 in the Xenical-treated patients and increased by an average of 0.31 kg/m2 in the placebo-treated patients (P =.001).

    Xenical Note

    Not Applicable

    Xenical Patient Counseling

    Patient Counseling

    Counsel patients to take a multivitamin containing fat-soluble vitamins and beta-carotene to ensure adequate nutrition; vitamin should be taken at least 2 hours before or after administration of Xenical, such as at bedtime.

    Ask about other medications as some may interact with Xenical (see Interactions).

    Inform patients of commonly observed side effects: oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation, fecal incontinence.

    Report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, dark urine, light colored stools, or right upper quadrant pain) while taking Xenical.

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