Indications for: XENICAL
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.
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).
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.
<12yrs: not established.
Pregnancy. Chronic malabsorption syndrome. Cholestasis.
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.
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).
GI effects (oily spotting, flatus with discharge, fecal urgency, fatty/oily stools, oily evacuation, increased defecation, fecal incontinence); cholelithiasis; rare: severe liver injury.
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.
Generic Drug Availability: