Buy Xenical

Xenical 120mg ( 90 pills) 166.88 Xenical 120mg (180 pills) 319.88 Xenical 120mg (270 pills) 479.88 Xenical 120mg (30 pills) 56 Xenical 120mg (60 pills) 109.88 IMPORTANT NOTE: The following information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist or other healthcare professional. It should not be construed to indicate that use of the drug is safe, appropriate, or effective for you. Consult your healthcare professional before using this drug. USES: This medication is used with a reduced-calorie diet to help significantly overweight persons lose weight. It also helps to prevent regaining weight previously lost. Orlistat works by blocking some of the fat normally digested by the intestine. HOW TO USE: Take this drug by mouth, generally three times daily during (or up to one hour after) each main meal that contains fat. Your daily intake of fat, protein and carbohydrate should be evenly spread over three main meals. If a meal is occasionally missed or contains no fat, skip that dose of the medication. Because this drug can interfere with absorption of fat-soluble vitamins (e.g., A,D,E,K), a daily multivitamin supplement containing these nutrients is recommended. Take the multivitamin at least 2 hours before or 2 hours after this drug (e.g., at bedtime). The effects of this drug may begin as soon as 1-2 days after treatment begins; noticeable weight loss will take longer. SIDE EFFECTS: Fatty/oily stool, oily spotting, intestinal gas with discharge, bowel movement urgency, poor bowel control, or headaches may occur. If these effects persist or worsen, notify your doctor promptly. Intestinal side effects (e.g., oily stool) may increase in intensity if you exceed your daily dietary fat allowance. If you notice other effects not listed above, contact your doctor or pharmacist. PRECAUTIONS: Tell your doctor your medical history, including: allergies, digestive disorders (malabsorption or cholestasis), low thyroid function (hypothyroidism), other metabolism problems (e.g., oxalate kidney stones, hyperoxaluria). This drug should not be used if you have anorexia nervosa or bulimia-type eating disorders. Tell your doctor if you are pregnant before using this medication. The manufacturer does not recommend use of this drug during pregnancy. It is not known whether this drug is excreted into breast milk. Because of the potential risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding. DRUG INTERACTIONS: Tell your doctor of all prescription and nonprescription medication you use, especially of: cyclosporine, "blood thinners" (e.g., warfarin), drugs for diabetes (e.g., insulin), other drugs used for weight loss. Cyclosporine should be taken at least 2 hours before or after orlistat to assure maximum absorption of the cyclosporine into your bloodstream. Do not start or stop any medicine without doctor or pharmacist approval. OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. NOTES: Do not share this medication with others. Follow your doctor-approved nutritional, reduced-calorie diet containing about 30 percent calories from fat. Also, exercise is recommended; however, first consult your doctor or pharmacist. MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up. STORAGE: Store at room temperature (77 degrees F, 25 degrees C) away from light and moisture. Welcome to XENICAL.com! XENICAL is a prescription medication that can help considerably overweight people lose weight and keep it off. We know that managing your weight can be frustrating, and sometimes you need a little extra support. Support you can't find in a pill alone. To succeed you may have to change the way you feel about food and about your body. To determine if you may be a candidate for XENICAL, your doctor will check your Body Mass Index -- a measure of weight which takes height into account. To find out your BMI now, use the convenient calculator below.Then be sure to register to receive an Evaluation Tool and personalized diet and exercise tips From our sponsors Learn about a treatment for nail fungus infection Breast Cancer: What you should know Internet Results Canadian Pharmacy Offers Xenical Compare these prices at a Canadian pharmacy. Xenical 120 mg - 84 for $97, 168 for $185, 252 for $274. Free shipping with no additional costs at Planetdrugsdirect. www.planetdrugsdirect.com Xenical 120mg: 84 Capsules for $95 Official site: Canada Drugs Online - licensed Canadian pharmacy. Providing great service, fast shipping and savings on medication. www.canadadrugsonline.com More internet results for xenical... Sponsored Results Xenical Orlistat blocks some of the fat that you eat from being absorbed by your body. Xenical (Advanced Consumer) Orlistat (OR-li-stat) is used as an aid to help you lose weight. The medicine prevents the digestion of some of the fat you eat. Fats that are not d... Spanish information for xenical... More Consumer Information for xenical... Professional Information Xenical Capsules XENICAL (orlistat) is a lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats. More Professional Information results for xenical... Additional Resources Internet Results for xenical See also Obesity Having trouble finding what you want? Try posting your query on the Drugs.com Community Discussion Boards A-Z List of Drug Names may help if you don't quite know how to spell the drug name. Drug Interactions Checker provides detailed information on drug-drug and drug-food interactions. Pill Identifier will help you identify an unknown pill by imprint code or shape/color. Image Search is helpful if you want to know what a certain pill looks like. News, FDA Approvals or In The Pipeline may help if the drug you are looking for is a new drug. Success With XENICAL Have you tried dieting, exercise and support groups, but found they never seem to work? Did you lose weight only to quickly gain it back? Your doctor will want to know these things before prescribing a medicine, to make sure that you've considered your options seriously and that your request for XENICAL isn't a hasty one. XENICAL is a prescription medication, not a magic pill that simply melts pounds away. The nice part about the XENICAL program is that it doesn't involve a complicated diet. In fact, the reduced-calorie diet with no more than 30% calories from fat is the same one recommended by the American Heart Association for all Americans. Keeping to a diet with no more than 30% calories from fat can be challenging for some people, especially if you enjoy things like fried foods and ice cream. If you can stay on the recommended diet, you will be on your way to achieving your weight-loss goals! XENICAL may be right for you if you have a Body Mass Index of 30 or greater, or have a BMI of 27 or greater and have other risk factors, such as high blood pressure, high cholesterol, heart disease or diabetes. Click here to calculate your BMI and find out if you might be a candidate for XENICAL. It is very important to talk to your doctor if you're considering using XENICAL as part of a weight-loss program. Click here for information and materials that you can print out and take to your next doctor XENICAL At Work If you eat an excessive amount of fat or calories, the excess is stored as fat by the body, resulting in weight gain. When you eat fat, your body breaks it down into its simplest components so that it can be digested. Unlike other weight-loss drugs you may have heard about that act in the brain or central nervous system to suppress appetite or to speed up metabolism, XENICAL works in your digestive system to block about one-third of the fat in the food you eat from being digested. Enzymes in your digestive system, called lipases, help digest (or break down) fat. When taken with meals, XENICAL attaches to the lipases and blocks them from breaking down some of the fat you have eaten. The undigested fat cannot be absorbed and is eliminated in your bowel movements. By working this way, XENICAL helps block about one-third of the fat in the foods you eat from being absorbed by your body. Taking XENICAL The recommended dose is one 120-mg capsule by mouth with liquid at each main meal that contains fat. You should take XENICAL up to three times a day in conjunction with a reduced-calorie diet. Each time you take XENICAL, your nutritionally balanced meal should contain no more than about 30% of calories from fat. You should evenly divide your daily intake of fat, carbohydrates and protein over three main meals. Take XENICAL during meals or up to 1 hour after a meal. If you occasionally miss a meal or have a meal without fat, you can omit your dose of XENICAL. Doses above 120-mg three times daily have not been shown to provide an additional weight-loss benefit. You should try to follow a healthy eating plan, such as the one developed by the American Heart Association. Following this eating plan will help you lose weight while decreasing some of the possible gastrointestinal effects you may experience while taking XENICAL. XENICAL interferes with your body's absorption of some fat-soluble vitamins. Therefore, when you use XENICAL, you should take a daily multivitamin supplement that contains vitamins D, E, and K and beta carotene. Take your multivitamin once a day at least 2 hours before or after taking XENICAL, such as at bedtime. To find out more about taking XENICAL properly, talk with your doctor. Click here for important patient information. How Do I Get XENICAL? Before your doctor can prescribe XENICAL, he or she will need to determine if this weight-loss approach is right for you. To do this, your doctor will need to review your medical history and evaluate your level of commitment. It is very important to talk to your doctor if you're considering using XENICAL as part of a weight-loss program. Your doctor will help you: Set realistic goals for weight loss Determine the right caloric level for your well-balanced, reduced-calorie diet that contains no more than 30% of calories from fat at each main meal Understand how to take XENICAL properly and why taking a multivitamin is so important To make your doctor visit most productive, you should be prepared to discuss your weight history, your goals and your level of commitment to a weight-loss program. We've put together a variety of resources to help make it easier for you: Materials to Take to Your Doctor Simply print out your Daily Food Diary and Personal Weight-Loss Worksheet, fill them in, and take them with you to your next doctor appointment. Preparing for Your Office Visit Talking with your doctor about weight loss can be difficult. To prepare for that conversation, check out this information that details what you can expect from a typical visit. Insurance Coverage and Reimbursement Find out if your insurance provider will cover the cost of XENICAL, and get tips on submitting your insurance claim. Controlling your weight is a great way to help stay healthy. Call your doctor or nutritionist today to set up an appointment Important Safety Information Indication XENICAL is for people who are considerably overweight (have a body mass index of 30 or greater). XENICAL is also for people who are overweight (have a body mass index of 27 or greater) and also have other risk factors such as high blood pressure, high cholesterol, heart disease or diabetes. XENICAL should be taken with a [nutritionally balanced] reduced-calorie diet containing no more than 30% of calories from fat. Contraindications/Warnings/Precautions XENICAL shouldn't be taken if you are pregnant, nursing, have food absorption problems or reduced bile flow. If you are taking cyclosporine, speak to your doctor before taking XENICAL. XENICAL reduces the absorption of vitamins, therefore, a daily multivitamin is recommended. Side Effects Because XENICAL works by blocking the absorption of dietary fat, it is likely that you will experience some changes in bowel habits. These bowel changes are a natural effect of blocking the fat from being absorbed. They generally occur during the first weeks of treatment; however, for some people they may continue for 6 months or longer while on XENICAL. These changes may include gas with oily discharge, an increased number of bowel movements, an urgent need to have them, and an inability to control them, particularly after meals containing higher amounts of fat than are recommended. Following a healthy eating plan, such as the one developed by the American Heart Association, will help you lose weight while decreasing some of the possible gastrointestinal effects you may experience while taking XENICAL. If you are concerned about these or any other side effects you experience while taking XENICAL, talk with your doctor or pharmacist. Click here for helpful information about talking with your doctor Manufacturer: Roche Pharmaceuticals Xenical Information: NO PRESCRIPTION IS REQUIRED. A DETAILED QUESTIONNAIRE WILL BE CONDUCTED. NO ORDER OF XENICAL WILL BE PROCESSED WITHOUT COMPLETION OF THIS QUESTIONNAIRE. Weight Loss Medications Xenical (Orlistat) is a gastrointestinal lipase inhibitor used to treat obesity. Xenical (Orlistat) is a medication that can help considerably overweight people lose weight and keep it off. We know that managing your weight can be frustrating, and sometimes you need a little extra support. Support you can't find in a pill alone. To succeed you may have to change the way you feel about food and about your body. If you eat an excessive amount of fat or calories, the excess is stored as fat by the body, resulting in weight gain. When you eat fat, your body breaks it down into its simplest components so that it can be digested. Unlike other weight-loss drugs you may have heard about that act in the brain or central nervous system to suppress appetite or to speed up metabolism, Xenical (Orlistat) works in your digestive system to block about one-third of the fat in the food you eat from being digested. Enzymes in your digestive system, called lipases, help digest (or break down) fat. When taken with meals, Xenical (Orlistat) attaches to the lipases and blocks them from breaking down some of the fat you have eaten. The undigested fat cannot be absorbed and is eliminated in your bowel movements. By working this way,Xenical (Orlistat) helps block about one-third of the fat in the foods you eat from being absorbed by your body. Xenical Side Effects: Xenical side effects that may occur while taking this medicine include oily stools or spotting, increased number of bowel movements, bowel movement urgency, poor bowel movement control, or gas with discharge. If Xenical side effects continue or are bothersome, check with your doctor. If you notice other Xenical side effects not listed above, contact your doctor, nurse, or pharmacist. Follow the directions for using XENICAL provided by your doctor. XENICAL COMES WITH A PATIENT Xenical Information LEAFLET. Read it carefully. Ask your doctor, nurse, or pharmacist any questions that you may have about this medicine. Take XENICAL with or up to 1 hour after each main meal that contains fat. Taking XENICAL with low-fat meals will lessen the side effects that can occur. If you miss a meal or the meal contains no fat, do not take a dose of XENICAL. IF YOU ARE TAKING A MULTIPLE VITAMIN, take it either 2 hours before or 2 hours after taking this medicine. STORE XENICAL at room temperature below 77 degrees F (25 degrees C), away from heat and light. IF YOU MISS A DOSE OF XENICAL, skip the missed dose and go back to your regular dosing schedule. Do NOT take 2 doses at once. Back to Main Drug Information Page Support for XENICAL Users Your doctor will help determine your weight loss goals and total number of daily calories, and provide you with a specific diet plan. Here are some tools and information to get you started. Daily Calorie Target Calculator Determine your caloric needs based on weight and activity level. Goal Activity Calculator Calculate your target weight to help set your weight loss goal. Percentage of Fat Calculator Find out how many grams of fat you should have each day. Per Serving Calculator Find out the calories of fat and the percentage of calories from fat per serving. Enhanced Calorie Calculator Choose from an extensive list of foods and serving sizes to calculate the total number of calories you've eaten in a meal. Guide to Nutrition Label Food packaging has all sorts of misleading claims, like "lite" and "reduced fat." Here you'll find important points to remember when reading nutrition labels. Dietary Fats: Fact or Fiction How much fat should you be eating? Are some fats worse than others? How can you check your diet for fat? Find out here. Bull's Eye Food Guide The Bull's Eye Food Guide system help you learn about the nutritional values of different foods and the recommended serving sizes of the food groups, so you can make wiser choices about what and how much you eat. Sample Diets Download a variety of printable recipes that meet the dietary requirements for XENICAL. BMI Calculator Body Mass Index is a measurement of weight taking height into account. To find out your BMI now, use the calculator located on the home page. Materials to Take to Your Doctor Here are some resources that can help you communicate effectively with your doctor. Simply print these materials out, fill them in and take them with you to your next doctor appointment. Insurance Letter - if your claim has been denied Use this convenient form to help you appeal denial of coverage for XENICAL from your insurance company. Insurance Letter - to request authorization of coverage Use this convenient form to help you request authorization of insurance coverage for your XENICAL prescription. type 2 diabetes treatment New Diabetes Treatment Breakthrough 99% Type 2 and 64% Type I Success Diabetes.IsCurable.com Do You Have Diabetes? Discover the Natural Key to Lose Fat, Gain Energy & Feel Great Diabetes.GlucoFast.com Diet Pills- Reviewed Get the Facts. See what products came out on top. Shop smart. www.ConsumerHealthDigest.com DESCRIPTION XENICAL (orlistat) is a lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats. Orlistat is (S)-2-formylamino-4-methyl-pentanoic acid (S)-1-[[(2S, 3S)-3-hexyl-4-oxo-2-oxetanyl] methyl]-dodecyl ester. Its empirical formula is C 29 H 53 NO 5 , and its molecular weight is 495.7. It is a single diastereomeric molecule that contains four chiral centers, with a negative optical rotation in ethanol at 529 nm. Orlistat is a white to off-white crystalline powder. Orlistat is practically insoluble in water, freely soluble in chloroform, and very soluble in methanol and ethanol. Orlistat has no p K a within the physiological pH range. XENICAL is available for oral administration in dark-blue, hard-gelatin capsules, with light-blue imprinting. Each capsule contains 120 mg of the active ingredient, orlistat. The capsules also contain the inactive ingredients microcrystalline cellulose, sodium starch glycolate, sodium lauryl sulfate, povidone, and talc. Each capsule shell contains gelatin, titanium dioxide, and FD&C Blue No.1, with printing of pharmaceutical glaze NF, titanium dioxide, and FD&C Blue No.1 aluminum lake. CLINICAL PHARMACOLOGY Mechanism of Action Orlistat is a reversible inhibitor of lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine residue site of gastric and pancreatic lipases. The inactivated enzymes are thus unavailable to hydrolyze dietary fat in the form of triglycerides into absorbable free fatty acids and monoglycerides. As undigested triglycerides are not absorbed, the resulting caloric deficit may have a positive effect on weight control. Systemic absorption of the drug is therefore not needed for activity. At the recommended therapeutic dose of 120 mg three times a day, orlistat inhibits dietary fat absorption by approximately 30%. Pharmacokinetics Absorption Systemic exposure to orlistat is minimal. Following oral dosing with 360 mg 14 C-orlistat, plasma radioactivity peaked at approximately 8 hours; plasma concentrations of intact orlistat were near the limits of detection (<5 ng/mL). In therapeutic studies involving monitoring of plasma samples, detection of intact orlistat in plasma was sporadic and concentrations were low (<10 ng/mL or 0.02 [micro ]M), without evidence of accumulation, and consistent with minimal absorption. The average absolute bioavailability of intact orlistat was assessed in studies with male rats at oral doses of 150 and 1000 mg/kg/day and in male dogs at oral doses of 100 and 1000 mg/kg/day and found to be 0.12%, 0.59% in rats and 0.7%, 1.9% in dogs, respectively. Distribution In vitro orlistat was >99% bound to plasma proteins (lipoproteins and albumin were major binding proteins). Orlistat minimally partitioned into erythrocytes. Metabolism Based on animal data, it is likely that the metabolism of orlistat occurs mainly within the gastrointestinal wall. Based on an oral 14 C-orlistat mass balance study in obese patients, two metabolites, M1 (4-member lactone ring hydrolyzed) and M3 (M1 with N-formyl leucine moiety cleaved), accounted for approximately 42% of total radioactivity in plasma. M1 and M3 have an open (beta)-lactone ring and extremely weak lipase inhibitory activity (1000- and 2500-fold less than orlistat, respectively). In view of this low inhibitory activity and the low plasma levels at the therapeutic dose (average of 26 ng/mL and 108 ng/mL for M1 and M3, respectively, 2 to 4 hours after a dose), these metabolites are considered pharmacologically inconsequential. The primary metabolite M1 had a short half-life (approximately 3 hours) whereas the secondary metabolite M3 disappeared at a slower rate (half-life approximately 13.5 hours). In obese patients, steady-state plasma levels of M1, but not M3, increased in proportion to orlistat doses. Elimination Following a single oral dose of 360 mg 14 C-orlistat in both normal weight and obese subjects, fecal excretion of the unabsorbed drug was found to be the major route of elimination. Orlistat and its M1 and M3 metabolites were also subject to biliary excretion. Approximately 97% of the administered radioactivity was excreted in feces; 83% of that was found to be unchanged orlistat. The cumulative renal excretion of total radioactivity was <2% of the given dose of 360 mg 14 C-orlistat. The time to reach complete excretion (fecal plus urinary) was 3 to 5 days. The disposition of orlistat appeared to be similar between normal weight and obese subjects. Based on limited data, the half-life of the absorbed orlistat is in the range of 1 to 2 hours. Special Populations Because the drug is minimally absorbed, studies in special populations (geriatric, different races, patients with renal and hepatic insufficiency) were not conducted. Pediatrics Plasma concentrations of orlistat and its metabolites M1 and M3 were similar to those found in adults at the same dose level. Daily fecal fat excretions were 27% and 7% of dietary intake in orlistat and placebo treatment groups, respectively. Drug-Drug Interactions Drug-drug interaction studies indicate that XENICAL had no effect on pharmacokinetics and/or pharmacodynamics of alcohol, digoxin, glyburide, nifedipine (extended-release tablets), oral contraceptives, phenytoin, pravastatin, or warfarin. Alcohol did not affect the pharmacodynamics of orlistat. Other Short-term Studies Adults In several studies of up to 6-weeks duration, the effects of therapeutic doses of XENICAL on gastrointestinal and systemic physiological processes were assessed in normal-weight and obese subjects. Postprandial cholecystokinin plasma concentrations were lowered after multiple doses of XENICAL in two studies but not significantly different from placebo in two other experiments. There were no clinically significant changes observed in gallbladder motility, bile composition or lithogenicity, or colonic cell proliferation rate, and no clinically significant reduction of gastric emptying time or gastric acidity. In addition, no effects on plasma triglyceride levels or systemic lipases were observed with the administration of XENICAL in these studies. In a 3-week study of 28 healthy male volunteers, XENICAL (120 mg three times a day) did not significantly affect the balance of calcium, magnesium, phosphorus, zinc, copper, and iron. Pediatrics In a 3-week study of 32 obese adolescents aged 12 to 16 years, XENICAL (120 mg three times a day) did not significantly affect the balance of calcium, magnesium, phosphorus, zinc, or copper. The iron balance was decreased by 64.7 [micro ]mole/24 hours and 40.4 [micro ]mole/24 hours in orlistat and placebo treatment groups, respectively. Dose-response Relationship A simple maximum effect (E max ) model was used to define the dose-response curve of the relationship between XENICAL daily dose and fecal fat excretion as representative of gastrointestinal lipase inhibition. The dose-response curve demonstrated a steep portion for doses up to approximately 400 mg daily, followed by a plateau for higher doses. At doses greater than 120 mg three times a day, the percentage increase in effect was minimal. CLINICAL STUDIES Observational epidemiologic studies have established a relationship between obesity and visceral fat and the risks for cardiovascular disease, type 2 diabetes, certain forms of cancer, gallstones, certain respiratory disorders, and an increase in overall mortality. These studies suggest that weight loss, if maintained, may produce health benefits for obese patients who have or are at risk of developing weight-related comorbidities. The long-term effects of orlistat on morbidity and mortality associated with obesity have not been established. 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 seven long-term (1- to 2-years duration) multicenter, double-blind, placebo-controlled clinical trials. During the first year of therapy, the studies of 2-year duration assessed weight loss and weight maintenance. During the second year of therapy, some studies assessed continued weight loss and weight maintenance and others assessed the effect of orlistat on weight regain. These studies included over 2800 patients treated with XENICAL and 1400 patients treated with placebo. The majority of these patients had obesity-related risk factors and comorbidities. In the XENDOS study, which included 3304 patients, the time to onset of type 2 diabetes was assessed in addition to weight management. In all these studies, treatment with XENICAL and placebo designates treatment with XENICAL plus diet and placebo plus diet, respectively. During the weight loss and weight maintenance period, a well-balanced, reduced-calorie diet that was intended to result in an approximate 20% decrease in caloric intake and provide 30% of calories from fat was recommended to all patients. In addition, all patients were offered nutritional counseling. One-year Results: Weight Loss, Weight Maintenance, and Risk Factors Weight loss was observed within 2 weeks of initiation of therapy and continued for 6 to 12 months. Pooled data from five clinical trials indicated that the overall mean weight loss from randomization to the end of 6 months and 1 year of treatment in the intent-to-treat population were 12.4 lbs and 13.4 lbs in the patients treated with XENICAL and 6.2 lbs and 5.8 lbs in the placebo-treated patients, respectively. During the 4-week placebo lead-in period of the studies, an additional 5 to 6 lb weight loss was also observed in the same patients. Of the patients who completed 1 year of treatment, 57% of the patients treated with XENICAL (120 mg three times a day) and 31% of the placebo-treated patients lost at least 5% of their baseline body weight. The percentages of patients achieving >/=5% and >/=10% weight loss after 1 year in five large multicenter studies for the intent-to-treat populations are presented in Table 1. The diet utilized during year 1 was a reduced-calorie diet. * Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet **/* Last observation carried forward **/** All studies, with the exception of 14161, were conducted at centers specialized in treating obesity and complications of obesity. Study 14161 was conducted with primary care physicians. The relative changes in risk factors associated with obesity following 1 year of therapy with XENICAL and placebo are presented for the population as a whole and for the population with abnormal values at randomization. Population as a Whole The changes in metabolic, cardiovascular and anthropometric risk factors associated with obesity based on pooled data for five clinical studies, regardless of the patient's risk factor status at randomization, are presented in Table 2. One year of therapy with XENICAL resulted in relative improvement in several risk factors. * Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet **/* Intent-to-treat population at week 52, observed data based on pooled data from 5 studies Xenical (orlistat) No Prescription for Xenical? Please email orders@planetdrugsdirect.com for help. BRAND NAME QTY 120mg - 84 capsule - $97.00 120mg - 168 capsule - $185.00 120mg - 252 capsule - $274.00 Manufacturer: Hoffmann-La Roche Rx: Only available by Prescription Description Chemical Name: ORLISTAT (OR-li-stat) This medicine is a gastrointestinal lipase inhibitor used in the management of obesity in adult and adolescent patients age 12 and older. This medicine may be used during the weight loss phase or following weight loss to assist in weight management. This medicine works by inhibiting the digestion of fats from the diet and should be used with a reduced-calorie diet. Directions Follow the directions for using this medicine provided by your doctor. THIS MEDICINE COMES WITH A PATIENT INFORMATION LEAFLET. Read it carefully. Ask your doctor, nurse, or pharmacist any questions that you may have about this medicine. Take this medicine with or up to 1 hour after each main meal that contains fat up to three per day. Taking this medicine with low-fat meals will lessen the side effects that can occur. If you miss a meal or the meal contains no fat, do not take a dose of this medicine. IF YOU ARE TAKING A MULTIPLE VITAMIN, take it either 2 hours before or 2 hours after taking this medicine. STORE THIS MEDICINE at room temperature below 77 degrees F (25 degrees C) in a tightly-closed container, away from heat and light. Brief storage between 59 and 86 degrees F (15 and 30 degrees C) is permitted. IF YOU MISS A DOSE OF THIS MEDICINE, skip the missed dose and go back to your regular dosing schedule. Do NOT take 2 doses at once. Cautions DO NOT TAKE THIS MEDICINE if you are allergic to it or are allergic to any ingredient in this product. DO NOT EXCEED THE RECOMMENDED DOSE. Exceeding the recommended dose will not make you lose more weight and may increase side effects. This medicine may reduce the absorption of necessary fat-soluble vitamins. To ensure that you are receiving adequate amounts of these vitamins, ask your doctor or pharmacist about the use of a vitamin supplement that would be right for you. KEEP ALL DOCTOR AND LABORATORY APPOINTMENTS while you are using this medicine. BEFORE YOU BEGIN TAKING ANY NEW MEDICINE, either prescription or over-the-counter, check with your doctor or pharmacist. This includes any other medicines used for weight loss/management. FOR WOMEN: IF YOU PLAN ON BECOMING PREGNANT, discuss with your doctor the benefits and risks of using this medicine during pregnancy. This medicine is not recommended for use during pregnancy. IT IS UNKNOWN IF THIS MEDICINE IS EXCRETED in breast milk. DO NOT BREAST-FEED while taking this medicine. IF YOU HAVE DIABETES, this medicine may affect your blood sugar. Check blood sugar levels closely and ask your doctor before adjusting the dose of your diabetes medicine. SIDE EFFECTS that may occur while taking this medicine include oily stools or spotting, increased number of bowel movements, bowel movement urgency, poor bowel movement control, or gas with discharge. If they continue or are bothersome, check with your doctor. AN ALLERGIC REACTION to this medicine is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include rash, itching, swelling, dizziness, or trouble breathing. If you notice other effects not listed above, contact your doctor, nurse, or pharmacist. Active Ingredients orlistat Losing weight. Of course it can make you look better. But even more important, it can make you feel better. Because the fact is that, in many cases, weight and health are closely related. Excess weight can contribute to high blood pressure, cholesterol and type 2 diabetes. The prescription medication from Roche is called XENICAL. XENICAL is a pill that is taken with meals and has been shown to reduce weight in considerably overweight people. It is FDA approved for people who are at least 30 pounds overweight depending on height. XENICAL does not act directly on the central nervous system. XENICAL should be taken with a reduced calorie diet containing no more than 30% of calories from fat. As with any prescription medication, XENICAL has possible side effects. Click here for important safety information. The long-term benefits of XENICAL on weight-related illnesses and life expectancy have not been evaluated. XENICAL is a prescription medication that can help considerably overweight people lose weight and keep it off. We know that managing your weight can be frustrating, and sometimes you need a little extra support. Support you can't find in a pill alone. To succeed you may have to change the way you feel about food and about your body. To determine if you may be a candidate for XENICAL, your doctor will check your Body Mass Index -- a measure of weight which takes height into account. To find out your BMI now, use the convenient calculator below.Then be sure to register to receive an Evaluation Tool and personalized diet and exercise tips If you eat an excessive amount of fat or calories, the excess is stored as fat by the body, resulting in weight gain. When you eat fat, your body breaks it down into its simplest components so that it can be digested. Unlike other weight-loss drugs you may have heard about that act in the brain or central nervous system to suppress appetite or to speed up metabolism, XENICAL works in your digestive system to block about one-third of the fat in the food you eat from being digested. Enzymes in your digestive system, called lipases, help digest (or break down) fat. When taken with meals, XENICAL attaches to the lipases and blocks them from breaking down some of the fat you have eaten. The undigested fat cannot be absorbed and is eliminated in your bowel movements. By working this way, XENICAL helps block about one-third of the fat in the foods you eat from being absorbed by your body. Xenical blocks absorption of dietary fat into the bloodstream, thereby reducing the number of calories you get from a meal. At the usual dosage level, it cuts fat absorption by almost one-third. Combined with a low-calorie diet, it is used to promote weight loss and discourage the return of unwanted pounds. The drug is prescribed for the frankly obese and for merely overweight people who have other health problems such as high blood pressure, diabetes, or high cholesterol levels. Your weight status is determined by your body mass index (BMI), a comparison of height to weight. -------------------------------------------------------------------------------- Most important fact about this drug Return to top Along with dietary fat, Xenical decreases the absorption of some fat-soluble vitamins and beta-carotene. To compensate, you should take a multivitamin containing vitamins A, E, D, and K once a day, at least 2 hours before or 2 hours after taking Xenical. -------------------------------------------------------------------------------- How should you take this medication? Return to top Take a capsule of Xenical during, or up to 1 hour after, each main meal. You should follow a nutritionally balanced, low-calorie diet that provides no more than 30 percent of its calories from fat. If you miss a meal, or the meal contains no fat, you can skip the accompanying dose of Xenical. --If you miss a dose... Resume taking Xenical at the next meal. Don't try to make up the loss with a double dose. The extra drug won't help. --Storage instructions... Store at room temperature, in a tightly sealed container. -------------------------------------------------------------------------------- What side effects may occur? Return to top Side effects of Xenical are more common during the first year of treatment. If any develop or change in intensity, inform your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Xenical. More common side effects may include: Abdominal discomfort or pain, anxiety, arthritis, back pain, diarrhea, dizziness, earache, fatigue, fatty or oily stools, fecal urgency or incontinence, flu, gas with fecal discharge, gum problems, headache, increased defecation, menstrual problems, muscle pain, nausea, oily discharge, rectal discomfort or pain, respiratory tract infections, skin rash, sleep problems, tooth problems, urinary tract infections, vaginal inflammation, vomiting Less common side effects may include: Dry skin, ear/nose/throat problems, joint disorders Side effects that usually occur after the first year of treatment with Xenical include: depression, leg pain, swollen feet, and tendonitis. -------------------------------------------------------------------------------- Why should this drug not be prescribed? Return to top Do not take Xenical if you suffer from "chronic malabsorption syndrome"--a condition that prevents nutrients from passing from your stomach into your bloodstream--or from cholestasis, a blockage in the supply of bile needed for digestion. You'll also need to avoid Xenical if it gives you an allergic reaction. -------------------------------------------------------------------------------- Special warnings about this medication Return to top Weight loss begins within 2 weeks and continues for 6 to 12 months. The effect of using Xenical for more than 2 years is still unknown. Side effects such as diarrhea and abdominal pain may be worse if you continue eating a high fat diet or even take a high-fat meal. Limit your fat intake. Your doctor will test your thyroid function before starting you on Xenical to make sure that your weight problem is not due to an underactive thyroid gland (hypothyroidism). Xenical is not an appropriate remedy for this problem. Xenical increases the likelihood of kidney stones. Use it with caution if you have a history of this problem. If you have diabetes, weight-loss is likely to reduce your blood sugar levels. If you're taking an oral diabetes medication or insulin, your dose may have to be reduced. Note that the safety and efficacy of this drug in children have not been established. -------------------------------------------------------------------------------- Possible food and drug interactions when taking this medication Return to top If Xenical is taken with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Xenical with the following: Cyclosporine (Neoral and Sandimmune) Warfarin (Coumadin) -------------------------------------------------------------------------------- Special information if you are pregnant or breastfeeding Return to top The effects of Xenical during pregnancy have not been adequately studied and the drug is not recommended for pregnant women. If you are pregnant or plan to become pregnant, inform your doctor immediately. It is not known whether Xenical appears in breast milk. Do not take it while breastfeeding. -------------------------------------------------------------------------------- Recommended dosage Return to top ADULTS -------------------------------------------------------------------------------- The recommended dose is one 120-milligram capsule 3 times daily with each main meal containing fat. -------------------------------------------------------------------------------- Overdosage Return to top The results of a massive overdose of Xenical are unknown, although the drug seems relatively harmless. However, any medication taken in excess can have serious consequences. If you suspect an overdose, seek medical attention.

XENICAL is a prescription medication that can help considerably overweight people lose weight and keep it off. We know that managing your weight can be frustrating, and sometimes you need a little extra support. Support you can't find in a pill alone. To succeed you may have to change the way you feel about food and about your body. To determine if you may be a candidate for XENICAL, your doctor will check your Body Mass Index -- a measure of weight which takes height into account. To find out your BMI now, use the convenient calculator below.Then be sure to register to receive an Evaluation Tool and personalized diet and exercise tips Have you tried dieting, exercise and support groups, but found they never seem to work? Did you lose weight only to quickly gain it back? Your doctor will want to know these things before prescribing a medicine, to make sure that you've considered your options seriously and that your request for XENICAL isn't a hasty one. XENICAL is a prescription medication, not a magic pill that simply melts pounds away. The nice part about the XENICAL program is that it doesn't involve a complicated diet. In fact, the reduced-calorie diet with no more than 30% calories from fat is the same one recommended by the American Heart Association for all Americans. Keeping to a diet with no more than 30% calories from fat can be challenging for some people, especially if you enjoy things like fried foods and ice cream. If you can stay on the recommended diet, you will be on your way to achieving your weight-loss goals! XENICAL may be right for you if you have a Body Mass Index of 30 or greater, or have a BMI of 27 or greater and have other risk factors, such as high blood pressure, high cholesterol, heart disease or diabetes. Click here to calculate your BMI and find out if you might be a candidate for XENICAL. It is very important to talk to your doctor if you're considering using XENICAL as part of a weight-loss program. Click here for information and materials that you can print out and take to your next doctor visit. If you eat an excessive amount of fat or calories, the excess is stored as fat by the body, resulting in weight gain. When you eat fat, your body breaks it down into its simplest components so that it can be digested. Unlike other weight-loss drugs you may have heard about that act in the brain or central nervous system to suppress appetite or to speed up metabolism, XENICAL works in your digestive system to block about one-third of the fat in the food you eat from being digested. Enzymes in your digestive system, called lipases, help digest (or break down) fat. When taken with meals, XENICAL attaches to the lipases and blocks them from breaking down some of the fat you have eaten. The undigested fat cannot be absorbed and is eliminated in your bowel movements. By working this way, XENICAL helps block about one-third of the fat in the foods you eat from being absorbed by your body. How Do I Get XENICAL? Before your doctor can prescribe XENICAL, he or she will need to determine if this weight-loss approach is right for you. To do this, your doctor will need to review your medical history and evaluate your level of commitment. It is very important to talk to your doctor if you're considering using XENICAL as part of a weight-loss program. Your doctor will help you: Set realistic goals for weight loss Determine the right caloric level for your well-balanced, reduced-calorie diet that contains no more than 30% of calories from fat at each main meal Understand how to take XENICAL properly and why taking a multivitamin is so important To make your doctor visit most productive, you should be prepared to discuss your weight history, your goals and your level of commitment to a weight-loss program. We've put together a variety of resources to help make it easier for you: Materials to Take to Your Doctor Simply print out your Daily Food Diary and Personal Weight-Loss Worksheet, fill them in, and take them with you to your next doctor appointment. Preparing for Your Office Visit Talking with your doctor about weight loss can be difficult. To prepare for that conversation, check out this information that details what you can expect from a typical visit. Insurance Coverage and Reimbursement Find out if your insurance provider will cover the cost of XENICAL, and get tips on submitting your insurance claim. Controlling your weight is a great way to help stay healthy. Call your doctor or nutritionist today to set up an appointment! What is Xenical used for? Xenical is used to help obese people who fit certain weight and height requirements lose weight and maintain weight loss. Xenical works in your intestines, where it blocks some of the fat you eat from being absorbed. This undigested fat is then eliminated in your bowel movements. Use Xenical together with a reduced-calorie diet. The weight management effects of Xenical continue only as long as you are taking it. Who should not take Xenical? You cannot take Xenical if you: have problems absorbing food have gallbladder problems are pregnant, or breast-feeding a child People with certain kidney problems may not be able to take Xenical. General Precautions with Xenical: Your daily intake of fat should be evenly divided over 3 main meals. Xenical can decrease the absorption some fat-soluble vitamins and beta-carotene. Therefore when being treated with Xenical, take a multivitamin supplement that contains vitamins D, E, K, and beta-carotene. Take your multivitamin once a day at least 2 hours before or after taking Xenical, such as bedtime. Review all medications that you are taking with your health care provider, including those that you take without a prescription. If you are taking cyclosporine you may have to be monitored more closely. If you are diabetic, Xenical may affect your blood sugar control. See your doctor regularly for monitoring and treatment adjustments. What should I tell my doctor or health care provider? Tell your health care provider if you are trying to become pregnant, are already pregnant, or are breast-feeding. What are some possible side effects of Xenical? (This is NOT a complete list of side effects reported with Xenical. Your health care provider can discuss with you a more complete list of side effects.) Oily spotting Gas with discharge Urgent need to have a bowel movement Oily or fatty stools Oily discharge Increased number of bowel movements Inability to control bowel movements For more detailed information about Xenical, ask your health care provider. Why is this drug prescribed? Return to top Xenical blocks absorption of dietary fat into the bloodstream, thereby reducing the number of calories you get from a meal. At the usual dosage level, it cuts fat absorption by almost one-third. Combined with a low-calorie diet, it is used to promote weight loss and discourage the return of unwanted pounds. The drug is prescribed for the frankly obese and for merely overweight people who have other health problems such as high blood pressure, diabetes, or high cholesterol levels. Your weight status is determined by your body mass index (BMI), a comparison of height to weight. -------------------------------------------------------------------------------- Most important fact about this drug Return to top Along with dietary fat, Xenical decreases the absorption of some fat-soluble vitamins and beta-carotene. To compensate, you should take a multivitamin containing vitamins A, E, D, and K once a day, at least 2 hours before or 2 hours after taking Xenical. -------------------------------------------------------------------------------- How should you take this medication? Return to top Take a capsule of Xenical during, or up to 1 hour after, each main meal. You should follow a nutritionally balanced, low-calorie diet that provides no more than 30 percent of its calories from fat. If you miss a meal, or the meal contains no fat, you can skip the accompanying dose of Xenical. --If you miss a dose... Resume taking Xenical at the next meal. Don't try to make up the loss with a double dose. The extra drug won't help. --Storage instructions... Store at room temperature, in a tightly sealed container. -------------------------------------------------------------------------------- What side effects may occur? Return to top Side effects of Xenical are more common during the first year of treatment. If any develop or change in intensity, inform your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Xenical. More common side effects may include: Abdominal discomfort or pain, anxiety, arthritis, back pain, diarrhea, dizziness, earache, fatigue, fatty or oily stools, fecal urgency or incontinence, flu, gas with fecal discharge, gum problems, headache, increased defecation, menstrual problems, muscle pain, nausea, oily discharge, rectal discomfort or pain, respiratory tract infections, skin rash, sleep problems, tooth problems, urinary tract infections, vaginal inflammation, vomiting Less common side effects may include: Dry skin, ear/nose/throat problems, joint disorders Side effects that usually occur after the first year of treatment with Xenical include: depression, leg pain, swollen feet, and tendonitis. -------------------------------------------------------------------------------- Why should this drug not be prescribed? Return to top Do not take Xenical if you suffer from "chronic malabsorption syndrome"--a condition that prevents nutrients from passing from your stomach into your bloodstream--or from cholestasis, a blockage in the supply of bile needed for digestion. You'll also need to avoid Xenical if it gives you an allergic reaction. -------------------------------------------------------------------------------- Special warnings about this medication Return to top Weight loss begins within 2 weeks and continues for 6 to 12 months. The effect of using Xenical for more than 2 years is still unknown. Side effects such as diarrhea and abdominal pain may be worse if you continue eating a high fat diet or even take a high-fat meal. Limit your fat intake. Your doctor will test your thyroid function before starting you on Xenical to make sure that your weight problem is not due to an underactive thyroid gland (hypothyroidism). Xenical is not an appropriate remedy for this problem. Xenical increases the likelihood of kidney stones. Use it with caution if you have a history of this problem. If you have diabetes, weight-loss is likely to reduce your blood sugar levels. If you're taking an oral diabetes medication or insulin, your dose may have to be reduced. Note that the safety and efficacy of this drug in children have not been established. -------------------------------------------------------------------------------- Possible food and drug interactions when taking this medication Return to top If Xenical is taken with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Xenical with the following: Cyclosporine (Neoral and Sandimmune) Warfarin (Coumadin) -------------------------------------------------------------------------------- Special information if you are pregnant or breastfeeding Return to top The effects of Xenical during pregnancy have not been adequately studied and the drug is not recommended for pregnant women. If you are pregnant or plan to become pregnant, inform your doctor immediately. It is not known whether Xenical appears in breast milk. Do not take it while breastfeeding. -------------------------------------------------------------------------------- Recommended dosage Return to top ADULTS -------------------------------------------------------------------------------- The recommended dose is one 120-milligram capsule 3 times daily with each main meal containing fat. -------------------------------------------------------------------------------- Overdosage Return to top The results of a massive overdose of Xenical are unknown, although the drug seems relatively harmless. However, any medication taken in excess can have serious consequences. If you suspect an overdose, seek medical attention. PDR Drug information for Xenical Capsules Manufacturer: Roche Laboratories DESCRIPTION XENICAL (orlistat) is a lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats. Orlistat is (S)-2-formylamino-4-methyl-pentanoic acid (S)-1-[[(2S, 3S)-3-hexyl-4-oxo-2-oxetanyl] methyl]-dodecyl ester. Its empirical formula is C 29 H 53 NO 5 , and its molecular weight is 495.7. It is a single diastereomeric molecule that contains four chiral centers, with a negative optical rotation in ethanol at 529 nm. Orlistat is a white to off-white crystalline powder. Orlistat is practically insoluble in water, freely soluble in chloroform, and very soluble in methanol and ethanol. Orlistat has no p K a within the physiological pH range. XENICAL is available for oral administration in dark-blue, hard-gelatin capsules, with light-blue imprinting. Each capsule contains 120 mg of the active ingredient, orlistat. The capsules also contain the inactive ingredients microcrystalline cellulose, sodium starch glycolate, sodium lauryl sulfate, povidone, and talc. Each capsule shell contains gelatin, titanium dioxide, and FD&C Blue No.1, with printing of pharmaceutical glaze NF, titanium dioxide, and FD&C Blue No.1 aluminum lake. CLINICAL PHARMACOLOGY Mechanism of Action Orlistat is a reversible inhibitor of lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine residue site of gastric and pancreatic lipases. The inactivated enzymes are thus unavailable to hydrolyze dietary fat in the form of triglycerides into absorbable free fatty acids and monoglycerides. As undigested triglycerides are not absorbed, the resulting caloric deficit may have a positive effect on weight control. Systemic absorption of the drug is therefore not needed for activity. At the recommended therapeutic dose of 120 mg three times a day, orlistat inhibits dietary fat absorption by approximately 30%. Pharmacokinetics Absorption Systemic exposure to orlistat is minimal. Following oral dosing with 360 mg 14 C-orlistat, plasma radioactivity peaked at approximately 8 hours; plasma concentrations of intact orlistat were near the limits of detection (<5 ng/mL). In therapeutic studies involving monitoring of plasma samples, detection of intact orlistat in plasma was sporadic and concentrations were low (<10 ng/mL or 0.02 [micro ]M), without evidence of accumulation, and consistent with minimal absorption. The average absolute bioavailability of intact orlistat was assessed in studies with male rats at oral doses of 150 and 1000 mg/kg/day and in male dogs at oral doses of 100 and 1000 mg/kg/day and found to be 0.12%, 0.59% in rats and 0.7%, 1.9% in dogs, respectively. Distribution In vitro orlistat was >99% bound to plasma proteins (lipoproteins and albumin were major binding proteins). Orlistat minimally partitioned into erythrocytes. Metabolism Based on animal data, it is likely that the metabolism of orlistat occurs mainly within the gastrointestinal wall. Based on an oral 14 C-orlistat mass balance study in obese patients, two metabolites, M1 (4-member lactone ring hydrolyzed) and M3 (M1 with N-formyl leucine moiety cleaved), accounted for approximately 42% of total radioactivity in plasma. M1 and M3 have an open (beta)-lactone ring and extremely weak lipase inhibitory activity (1000- and 2500-fold less than orlistat, respectively). In view of this low inhibitory activity and the low plasma levels at the therapeutic dose (average of 26 ng/mL and 108 ng/mL for M1 and M3, respectively, 2 to 4 hours after a dose), these metabolites are considered pharmacologically inconsequential. The primary metabolite M1 had a short half-life (approximately 3 hours) whereas the secondary metabolite M3 disappeared at a slower rate (half-life approximately 13.5 hours). In obese patients, steady-state plasma levels of M1, but not M3, increased in proportion to orlistat doses. Elimination Following a single oral dose of 360 mg 14 C-orlistat in both normal weight and obese subjects, fecal excretion of the unabsorbed drug was found to be the major route of elimination. Orlistat and its M1 and M3 metabolites were also subject to biliary excretion. Approximately 97% of the administered radioactivity was excreted in feces; 83% of that was found to be unchanged orlistat. The cumulative renal excretion of total radioactivity was <2% of the given dose of 360 mg 14 C-orlistat. The time to reach complete excretion (fecal plus urinary) was 3 to 5 days. The disposition of orlistat appeared to be similar between normal weight and obese subjects. Based on limited data, the half-life of the absorbed orlistat is in the range of 1 to 2 hours. Special Populations Because the drug is minimally absorbed, studies in special populations (geriatric, different races, patients with renal and hepatic insufficiency) were not conducted. Pediatrics Plasma concentrations of orlistat and its metabolites M1 and M3 were similar to those found in adults at the same dose level. Daily fecal fat excretions were 27% and 7% of dietary intake in orlistat and placebo treatment groups, respectively. Drug-Drug Interactions Drug-drug interaction studies indicate that XENICAL had no effect on pharmacokinetics and/or pharmacodynamics of alcohol, digoxin, glyburide, nifedipine (extended-release tablets), oral contraceptives, phenytoin, pravastatin, or warfarin. Alcohol did not affect the pharmacodynamics of orlistat. Other Short-term Studies Adults In several studies of up to 6-weeks duration, the effects of therapeutic doses of XENICAL on gastrointestinal and systemic physiological processes were assessed in normal-weight and obese subjects. Postprandial cholecystokinin plasma concentrations were lowered after multiple doses of XENICAL in two studies but not significantly different from placebo in two other experiments. There were no clinically significant changes observed in gallbladder motility, bile composition or lithogenicity, or colonic cell proliferation rate, and no clinically significant reduction of gastric emptying time or gastric acidity. In addition, no effects on plasma triglyceride levels or systemic lipases were observed with the administration of XENICAL in these studies. In a 3-week study of 28 healthy male volunteers, XENICAL (120 mg three times a day) did not significantly affect the balance of calcium, magnesium, phosphorus, zinc, copper, and iron. Pediatrics In a 3-week study of 32 obese adolescents aged 12 to 16 years, XENICAL (120 mg three times a day) did not significantly affect the balance of calcium, magnesium, phosphorus, zinc, or copper. The iron balance was decreased by 64.7 [micro ]mole/24 hours and 40.4 [micro ]mole/24 hours in orlistat and placebo treatment groups, respectively. Dose-response Relationship A simple maximum effect (E max ) model was used to define the dose-response curve of the relationship between XENICAL daily dose and fecal fat excretion as representative of gastrointestinal lipase inhibition. The dose-response curve demonstrated a steep portion for doses up to approximately 400 mg daily, followed by a plateau for higher doses. At doses greater than 120 mg three times a day, the percentage increase in effect was minimal. CLINICAL STUDIES Observational epidemiologic studies have established a relationship between obesity and visceral fat and the risks for cardiovascular disease, type 2 diabetes, certain forms of cancer, gallstones, certain respiratory disorders, and an increase in overall mortality. These studies suggest that weight loss, if maintained, may produce health benefits for obese patients who have or are at risk of developing weight-related comorbidities. The long-term effects of orlistat on morbidity and mortality associated with obesity have not been established. 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 seven long-term (1- to 2-years duration) multicenter, double-blind, placebo-controlled clinical trials. During the first year of therapy, the studies of 2-year duration assessed weight loss and weight maintenance. During the second year of therapy, some studies assessed continued weight loss and weight maintenance and others assessed the effect of orlistat on weight regain. These studies included over 2800 patients treated with XENICAL and 1400 patients treated with placebo. The majority of these patients had obesity-related risk factors and comorbidities. In the XENDOS study, which included 3304 patients, the time to onset of type 2 diabetes was assessed in addition to weight management. In all these studies, treatment with XENICAL and placebo designates treatment with XENICAL plus diet and placebo plus diet, respectively. During the weight loss and weight maintenance period, a well-balanced, reduced-calorie diet that was intended to result in an approximate 20% decrease in caloric intake and provide 30% of calories from fat was recommended to all patients. In addition, all patients were offered nutritional counseling. One-year Results: Weight Loss, Weight Maintenance, and Risk Factors Weight loss was observed within 2 weeks of initiation of therapy and continued for 6 to 12 months. Pooled data from five clinical trials indicated that the overall mean weight loss from randomization to the end of 6 months and 1 year of treatment in the intent-to-treat population were 12.4 lbs and 13.4 lbs in the patients treated with XENICAL and 6.2 lbs and 5.8 lbs in the placebo-treated patients, respectively. During the 4-week placebo lead-in period of the studies, an additional 5 to 6 lb weight loss was also observed in the same patients. Of the patients who completed 1 year of treatment, 57% of the patients treated with XENICAL (120 mg three times a day) and 31% of the placebo-treated patients lost at least 5% of their baseline body weight. The percentages of patients achieving >/=5% and >/=10% weight loss after 1 year in five large multicenter studies for the intent-to-treat populations are presented in Table 1. The changes from randomization following 1-year treatment in the population with abnormal lipid levels (LDL >/=130 mg/dL, LDL/HDL >/=3.5, HDL <35 mg/dL) were greater for XENICAL compared to placebo with respect to LDL-cholesterol (-7.83% vs +1.14%) and the LDL/HDL ratio (-0.64 vs -0.46). HDL increased in the placebo group by 20.1% and in the XENICAL group by 18.8%. In the population with abnormal blood pressure at baseline (systolic BP >/=140 mm Hg), the change in SBP from randomization to 1 year was greater for XENICAL (-10.89 mm Hg) than placebo (-5.07 mm Hg). For patients with a diastolic blood pressure >/=90 mm Hg, XENICAL patients decreased by -7.9 mm Hg while the placebo patients decreased by -5.5 mm Hg. Fasting insulin decreased more for XENICAL than placebo (-39 vs -16 pmol/L) from randomization to 1 year in the population with abnormal baseline values (>/=120 pmol/L). A greater reduction in waist circumference for XENICAL vs placebo (-7.29 vs -4.53 cm) was observed in the population with abnormal baseline values (>/=100 cm). Effect on Weight Regain Three studies were designed to evaluate the effects of XENICAL compared to placebo in reducing weight regain after a previous weight loss achieved following either diet alone (one study, 14302) or prior treatment with XENICAL (two studies, 14119C and 14185). The diet utilized during the 1-year weight regain portion of the studies was a weight-maintenance diet, rather than a weight-loss diet, and patients received less nutritional counseling than patients in weight-loss studies. For studies 14119C and 14185, patients' previous weight loss was due to 1 year of treatment with XENICAL in conjunction with a mildly hypocaloric diet. Study 14302 was conducted to evaluate the effects of 1 year of treatment with XENICAL on weight regain in patients who had lost 8% or more of their body weight in the previous 6 months on diet alone. In 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<0.001). In 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<0.001). In 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<0.001). 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 previously discussed (see Table 1). At the end of year 1, the patients' diets were reviewed and changed where necessary. The diet prescribed in the second year was designed to maintain patient's current weight. XENICAL was shown to be more effective than placebo in long-term weight control in four large, multicenter, 2-year double-blind, placebo-controlled studies. Pooled data from four clinical studies indicate that 40% of all patients treated with 120 mg three times a day of XENICAL and 24% of patients treated with placebo who completed 2 years of the same therapy had >/=5% loss of body weight from randomization. Pooled data from four clinical studies indicate that the relative weight loss advantage between XENICAL 120 mg three times a day and placebo treatment groups was the same after 2 years as for 1 year, indicating that the pharmacologic advantage of XENICAL was maintained over 2 years. In the same studies cited in the One-year Results (see Table 1), the percentages of patients achieving a >/=5% and >/=10% weight loss after 2 years are shown in Table 3. addition, XENICAL (n=162) compared to placebo (n=159) was associated with significant lowering for total cholesterol (-1.0% vs +9.0%, p0.05. Systolic blood pressure increased by +0.61 mm Hg on XENICAL and increased by +4.33 mm Hg on placebo, p>0.05. Diastolic blood pressure decreased by -0.47 mm Hg for XENICAL and by -0.5 mm Hg for placebo, p>0.05. Glucose Tolerance in Obese Patients Two-year studies that included oral glucose tolerance tests were conducted in obese patients not previously diagnosed or treated for type 2 diabetes and whose baseline oral glucose tolerance test (OGTT) status at randomization was either normal, impaired, or diabetic. The progression from a normal OGTT at randomization to a diabetic or impaired OGTT following 2 years of treatment with XENICAL (n=251) or placebo (n=207) were compared. Following treatment with XENICAL, 0.0% and 7.2% of the patients progressed from normal to diabetic and normal to impaired, respectively, compared to 1.9% and 12.6% of the placebo treatment group, respectively. In patients found to have an impaired OGTT at randomization, the percent of patients improving to normal or deteriorating to diabetic status following 1 and 2 years of treatment with XENICAL compared to placebo are presented. After 1 year of treatment, 45.8% of the placebo patients and 73% of the XENICAL patients had a normal oral glucose tolerance test while 10.4% of the placebo patients and 2.6% of the XENICAL patients became diabetic. After 2 years of treatment, 50% of the placebo patients and 71.7% of the XENICAL patients had a normal oral glucose tolerance test while 7.5% of placebo patients were found to be diabetic and 1.7% of XENICAL patients were found to be diabetic after treatment. Onset of Type 2 Diabetes in Obese Patients In the XENDOS trial, in the overall population, orlistat delayed the onset of type 2 diabetes such that at the end of four years of treatment the cumulative incidence rate of diabetes was 8.3% for the placebo group compared to 5.5% for the orlistat group, p=0.01 (see Table 6). This finding was driven by a statistically-significant reduction in the incidence of developing type 2 diabetes in those patients who had impaired glucose tolerance at baseline (Table 6 and Figure 2). Orlistat did not reduce the risk for the development of diabetes in patients with normal glucose tolerance at baseline. The effect of XENICAL to delay the onset of type 2 diabetes in obese patients with IGT is presumably due to weight loss, and not to any independent effects of the drug on glucose or insulin metabolism. The effect of orlistat on weight loss is adjunctive to diet and exercise. 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 (357 receiving XENICAL 120 mg three times a day, 182 receiving placebo), aged 12 to 16 years. All study participants had a baseline BMI that was 2 units greater than the US weighted mean for the 95 th percentile based on age and gender. Body mass index was the primary efficacy parameter because it takes into account changes in height and body weight, which occur in growing children. During the study, all patients were instructed to take a multivitamin containing fat-soluble vitamins at least 2 hours before or after ingestion of XENICAL. Patients were also maintained on a well-balanced, reduced-calorie diet that was intended to provide 30% of calories from fat. In addition, all patients were placed on a behavior modification program and offered exercise counseling. Approximately 65% of patients in each treatment group completed the study. Following one year of treatment, BMI decreased by an average of 0.55 kg/m 2 in the XENICAL-treated patients and increased by an average of 0.31 kg/m 2 in the placebo-treated patients (p=0.001). The percentages of patients achieving >/=5% and >/=10% reduction in BMI and body weight after 52 weeks of treatment for the intent-to-treat population are Xenical This page contains drug information on Xenical. The information provided includes the following: what is Xenical the possible side effects of Xenical what happens if you miss a dose of Xenical what happens if you overdose with Xenical the most important information about Xenical how to use Xenical other drugs that may affect Xenical what to avoid while using Xenical Generic Name: orlistat (OR lih stat) Brand Names: Xenical What is the most important information I should know about orlistat? • Orlistat may decrease your body's absorption of some fat-soluble vitamins. To ensure adequate nutrition, your doctor may recommend taking a multivitamin that contains vitamins D, E, K, and beta-carotene. Take your vitamin supplement once a day, at least 2 hours before or after a dose of orlistat. • Do not take more of this medication than has been prescribed for you. Doses greater than 120 mg three times a day have not been shown to provide any additional weight-loss benefit. What is orlistat? • Orlistat blocks some of the fat that you eat from being absorbed by your body. • Orlistat is used in the management of obesity including weight loss and weight maintenance when used with a reduced-calorie diet. • Orlistat may also be used for purposes other than those listed in this medication guide. What should I discuss with my healthcare provider before taking orlistat? • Do not take orlistat without first talking to your doctor if you have · chronic malabsorption syndrome (an inability to absorb food and nutrients properly), or · gallbladder problems. • You may not be able to take orlistat if you have any of the conditions listed above. • Before taking orlistat, talk to your doctor if you · have a history of kidney stones, · have diabetes, · have anorexia or bulimia, · take any other weight-loss medicine, or · take cyclosporine (Sandimmune, Neoral). • You may not be able to take orlistat, or you may require a dosage adjustment or special monitoring during your treatment if you have any of the conditions listed above. • Orlistat is in the FDA pregnancy category B. This means that it is not expected to harm an unborn baby. Do not take orlistat without first talking to your doctor if you are pregnant. • It is not known whether orlistat passes into breast milk. Do not take orlistat without first talking to your doctor if you are breast-feeding a baby. How should I take orlistat? • Take orlistat exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you. • Take each dose with a full glass of water. • Orlistat is usually taken with each main meal that contains fat. Orlistat can be taken during meals or up to one hour after a meal. • Each time you take orlistat, your meal should contain no more than about 30% of calories from fat. Evenly divide your daily intake of fat, carbohydrates, and protein over three main meals a day. Talk to your doctor about following a healthy eating plan. • If you miss a meal, or if you have a meal without fat, you can skip your dose of orlistat for that meal also. • If orlistat is taken with any one meal that is very high in fat, there is an increased chance of digestive side effects. • Do not take more of this medication than has been prescribed for you. Doses greater than 120 mg three times a day have not been shown to provide an additional weight-loss benefit. • Orlistat may decrease your body's absorption of some fat-soluble vitamins. To ensure adequate nutrition, your doctor may recommend taking a multivitamin that contains vitamins D, E, K, and beta-carotene. Take your vitamin supplement once a day, at least 2 hours before or after a dose of orlistat. • Store orlistat at room temperature away from moisture and heat. What happens if I miss a dose? • Take the missed dose up to one hour after a meal. If more than one hour has passed since your last meal, skip the dose you missed and take only your next regularly scheduled dose as directed. Do not take a double dose of this medication. • If you miss a meal, or if you have a meal without fat, you can skip your dose of orlistat for that meal also. What happens if I overdose? • Seek emergency medical attention. • Symptoms of an orlistat overdose are not known. What should I avoid while taking orlistat? • Each time you take orlistat, your meal should contain no more than about 30% of calories from fat. Evenly divide your daily intake of fat, carbohydrates, and protein over three main meals a day. Talk to your doctor about following a healthy eating plan. What are the possible side effects of orlistat? • Stop taking orlistat and seek emergency medical attention if you experience a rare allergic reaction including shortness of breath; closing of your throat; swelling of your lips, tongue, or face; or hives. • Other, less serious side effects are more likely to occur. Continue to take orlistat and talk to your doctor if you experience · oily spotting; · oily or fatty stools; · orange or brown colored oil in your stool; · gas with discharge, an oily discharge; · an urgent need to go to the bathroom; · an inability to control bowel movements, or; · an increased number of bowel movements. • The bowel changes listed above are a natural effect of blocking fat and indicate that orlistat is working. They generally occur early in treatment, particularly after meals containing higher amounts of fat than are recommended. These symptoms are usually temporary and lessen or disappear as you continue treatment and keep to your recommended diet of meals containing 30% fat. • Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. What other drugs will affect orlistat? • Do not take orlistat without first talking to your doctor if you are taking any of the following medicines: · cyclosporine (Neoral, Sandimmune), or · warfarin (Coumadin). • You may not be able to take orlistat, or you may require a dosage adjustment or special monitoring during your treatment if you are taking any of the medicines listed above. • Orlistat may decrease your body's absorption of some fat-soluble vitamins. To ensure adequate nutrition, your doctor may recommend taking a multivitamin that contains vitamins D, E, K, and beta-carotene. Take your vitamin supplement once a day, at least 2 hours before or after a dose of orlistat. • Drugs other than those listed here may also interact with orlistat. Talk to your doctor and pharmacist before taking or using any other prescription or over-the-counter medicines including vitamins, minerals, and herbal products. Where can I get more information? • Your pharmacist has more information about orlistat written for health professionals that you may read. XENICAL is contraindicated in patients with chronic malabsorption syndrome or cholestasis, and in patients with known hypersensitivity to XENICAL or to any component of this product. WARNINGS Miscellaneous Organic causes of obesity (eg, hypothyroidism) should be excluded before prescribing XENICAL. Preliminary 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 coadministered. To reduce the chance of a drug-drug interaction, cyclosporine should be taken at least 2 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. PRECAUTIONS General Patients should be advised to adhere to dietary guidelines (see DOSAGE AND ADMINISTRATION ). Gastrointestinal events (see ADVERSE REACTIONS ) 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. 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 ). 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. Table 9 illustrates the percentage of adult patients on XENICAL and placebo who developed a low vitamin level on two or more consecutive visits during 1 and 2 years of therapy in studies in which patients were not previously receiving vitamin supplementation. Some patients may develop increased levels of urinary oxalate following treatment with XENICAL. Caution should be exercised when prescribing XENICAL to patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis. Weight-loss induction by XENICAL may be accompanied by improved metabolic control in diabetics, which might require a reduction in dose of oral hypoglycemic medication (eg, sulfonylureas, metformin) or insulin (see CLINICAL STUDIES ). Misuse Potential 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 INDICATIONS AND USAGE for recommended prescribing guidelines. Information for Patients Patients should read the Patient Information before starting treatment with XENICAL and each time their prescription is renewed. Drug Interactions Alcohol In a multiple-dose study in 30 normal-weight subjects, coadministration of XENICAL and 40 grams of alcohol (eg, approximately 3 glasses of wine) did not result in alteration of alcohol pharmacokinetics, orlistat pharmacodynamics (fecal fat excretion), or systemic exposure to orlistat. Cyclosporine Preliminary data from a XENICAL and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when XENICAL was coadministered with cyclosporine (see WARNINGS ). Digoxin In 12 normal-weight subjects receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not alter the pharmacokinetics of a single dose of digoxin. Fat-soluble Vitamin Supplements and Analogues A pharmacokinetic interaction study showed a 30% reduction in beta-carotene supplement absorption when concomitantly administered with XENICAL. XENICAL inhibited absorption of a vitamin E acetate supplement by approximately 60%. The effect of orlistat on the absorption of supplemental vitamin D, vitamin A, and nutritionally-derived vitamin K is not known at this time. Glyburide In 12 normal-weight subjects receiving orlistat 80 mg three times a day for 5 days, orlistat did not alter the pharmacokinetics or pharmacodynamics (blood glucose-lowering) of glyburide. Nifedipine (extended-release tablets) In 17 normal-weight subjects receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not alter the bioavailability of nifedipine (extended-release tablets). Oral Contraceptives In 20 normal-weight female subjects, the treatment of XENICAL 120 mg three times a day for 23 days resulted in no changes in the ovulation-suppressing action of oral contraceptives. Phenytoin In 12 normal-weight subjects receiving XENICAL 120 mg three times a day for 7 days, XENICAL did not alter the pharmacokinetics of a single 300-mg dose of phenytoin. Pravastatin In a 2-way crossover study of 24 normal-weight, mildly hypercholesterolemic patients receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not affect the pharmacokinetics of pravastatin. Warfarin In 12 normal-weight subjects, administration of XENICAL 120 mg three times a day for 16 days did not result in any change in either warfarin pharmacokinetics (both R- and S-enantiomers) or pharmacodynamics (prothrombin time and serum Factor VII). Although undercarboxylated osteocalcin, a marker of vitamin K nutritional status, was unaltered with XENICAL administration, vitamin K levels tended to decline in subjects taking XENICAL. Therefore, as vitamin K absorption may be decreased with XENICAL, patients on chronic stable doses of warfarin who are prescribed XENICAL should be monitored closely for changes in coagulation parameters. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies in rats and mice did not show a carcinogenic potential for orlistat at doses up to 1000 mg/kg/day and 1500 mg/kg/day, respectively. For mice and rats, these doses are 38 and 46 times the daily human dose calculated on an area under concentration vs time curve basis of total drug-related material. Orlistat had no detectable mutagenic or genotoxic activity as determined by the Ames test, a mammalian forward mutation assay (V79/HPRT), an in vitro clastogenesis assay in peripheral human lymphocytes, an unscheduled DNA synthesis assay (UDS) in rat hepatocytes in culture, and an in vivo mouse micronucleus test. When given to rats at a dose of 400 mg/kg/day in a fertility and reproduction study, orlistat had no observable adverse effects. This dose is 12 times the daily human dose calculated on a body surface area (mg/m 2 ) basis. Pregnancy Teratogenic Effects: Pregnancy Category B. Teratogenicity studies were conducted in rats and rabbits at doses up to 800 mg/kg/day. Neither study showed embryotoxicity or teratogenicity. This dose is 23 and 47 times the daily human dose calculated on a body surface area (mg/m 2 ) basis for rats and rabbits, respectively. The incidence of dilated cerebral ventricles was increased in the mid- and high-dose groups of the rat teratology study. These doses were 6 and 23 times the daily human dose calculated on a body surface area (mg/m 2 ) basis for the mid- and high-dose levels, respectively. This finding was not reproduced in two additional rat teratology studies at similar doses. There are no adequate and well-controlled studies of XENICAL in pregnant women. Because 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 orlistat is secreted in human milk. Therefore, XENICAL should not be taken by nursing women. Pediatric Use The safety and efficacy of XENICAL have been evaluated in obese adolescent patients aged 12 to 16 years. Use of XENICAL in this age group is supported by evidence from adequate and well-controlled studies of XENICAL in adults with additional data from a 54-week efficacy and safety study and a 21-day mineral balance study in obese adolescent patients aged 12 to 16 years. Patients treated with XENICAL had a mean reduction in BMI of 0.55 kg/m 2 compared with an average increase of 0.31 kg/m 2 in placebo-treated patients (p=0.001). In both adolescent studies, adverse effects were generally similar to those described in adults and included fatty/oily stool, oily spotting, and oily evacuation. In a subgroup of 152 orlistat and 77 placebo patients from the 54-week study, changes in body composition measured by DEXA were similar in both treatment groups with the exception of fat mass, which was significantly reduced in patients treated with XENICAL compared to patients treated with placebo (-2.5 kg vs -0.6 kg, p=0.033). Because XENICAL can interfere with the absorption of fat-soluble vitamins, all patients should take a daily multivitamin that contains vitamins A, D, E, K, and beta-carotene. The supplement should be taken at least 2 hours before or after XENICAL (see CLINICAL PHARMACOLOGY : Other Short-term Studies ; CLINICAL STUDIES : Pediatric Clinical Studies ; ADVERSE REACTIONS : Pediatric Patients ). XENICAL has not been studied in pediatric patients below the age of 12 years. Geriatric Use 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. ADVERSE REACTIONS Commonly Observed (based on first year and second year data - XENICAL 120 mg three times a day versus placebo): Gastrointestinal (GI) symptoms were the most commonly observed treatment-emergent adverse events associated with the use of XENICAL in the seven double-blind, placebo-controlled clinical trials and are primarily a manifestation of the mechanism of action. (Commonly observed is defined as an incidence of >/=5% and an incidence in the XENICAL 120 mg group that is at least twice that of placebo.)

Orlistat (marketed as Xenical® by Roche) is a drug designed to treat obesity. Its primary function is to prevent the absorption of dietary fats, thereby reducing caloric intake. It is intended for use in conjunction with a physician-supervised reduced calorie diet. Contents [hide] 1 Pharmacology 2 Efficacy 3 Side effects 4 Contraindications 5 Availability 6 References 7 External links [edit] Pharmacology Orlistat works by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. Without this enzyme, triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested. Only trace amounts of orlistat are absorbed systemically, the primary effect is local lipase inhibition within the GI tract after an oral dose. The primary route of elimination is through the feces. At the standard prescription dose of 120 mg three times daily before meals, orlistat prevents approximately 30% of dietary fat from being absorbed.[1] [edit] Efficacy The amount of weight loss achieved with orlistat is variable. In 1 year clinical trials, between 35.5% and 54.8% of subjects achieved a 5% or greater decrease in body mass. Between 16.4% and 24.8% achieved at least a 10% decrease in body mass. A significant amount of subjects regained the weight after they stopped using orlistat. Despite this cosmetically small effect, there was a 37% reduction in the incidence of Type 2 diabetes,[2] a significant difference. [edit] Side effects The primary side effects of the drug are GI-related. Side effects were most severe within the first year of therapy. Because its main effect is to prevent dietary fat from being absorbed, the fat is excreted unchanged in the feces and so the stool may become oily or loose. Increased flatulence is also common. Bowel movements may become frequent or urgent. Rare occurrence of fecal incontinence have been seen in clinical trials. To minimize these effects, foods with high fat content should be avoided. The absorption of fat-soluble vitamins are inhibited by the use of orlistat. A multivitamin tablet containing these vitamins (D, E, A and beta-carotene) should be taken once a day, at least 2 hours before or after taking the drug. Concern was raised by the FDA regarding a possible link between Orlistat and breast cancer after reviewing a clinical trial in which 1016 women were given orlistat, with ten of these patients later going on to develop breast cancer. Only one woman from the placebo group, containing 579 patients, suffered this complication. Roughly a four to seven fold increase in the probability of developing breast cancer as a result of orlistat use has been suggested.[citation needed] A recent animal study addressed a connection orlistat shares with aberrant crypt foci (ACF) in the colon, which is believed to be one of the earliest precursors of colon cancer.[3] [edit] Contraindications Xenical is contraindicated in: Malabsorption Reduced gallbladder function (e.g. after cholecystectomy) Pregnancy and breastfeeding Certain kidney problems [edit] Availability In most areas orlistat is available by prescription only. In 2004, a lower-dose version of the drug (60 mg compared to 120 mg for the prescription version) was released over the counter in Australia and New Zealand; the United States is expected to follow in the near future. On January 23, 2006, a US Food and Drug Administration advisory panel voted 11 to 3 to recommend the approval of an OTC formulation of orlistat (planned to be marketed under the name "Alli" by GlaxoSmithKline).[4] The proposed product will consist of 60 mg dosage units, similar to the OTC products available elsewhere. [edit] References ^ (2006) 2006 Physicians' Desk Reference (PDR). Thomson PDR. ISBN 1563635275. ^ Torgerson J, Hauptman J, Boldrin M, Sjostrom L (2004). "XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.". Diabetes Care 27 (1): 155-61. PMID 14693982. ^ Garcia S, da Costa Barros L, Turatti A, Martinello F, Modiano P, Ribeiro-Silva A, de Oliveira Vespucio M, Uyemura S (2006). "The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen.". Cancer Lett 240 (2): 221-4. PMID 16377080. ^ "Panel Supports Offering Diet Pill Orlistat Over the Counter", Washington Post, January 24, 2006, pp. A02. Retrieved on 2006-08-10. [edit] External links Xenical This page contains drug information on Xenical. The information provided includes the following: what is Xenical the possible side effects of Xenical what happens if you miss a dose of Xenical what happens if you overdose with Xenical the most important information about Xenical how to use Xenical other drugs that may affect Xenical what to avoid while using Xenical Generic Name: orlistat (OR lih stat) Brand Names: Xenical What is the most important information I should know about orlistat? • Orlistat may decrease your body's absorption of some fat-soluble vitamins. To ensure adequate nutrition, your doctor may recommend taking a multivitamin that contains vitamins D, E, K, and beta-carotene. Take your vitamin supplement once a day, at least 2 hours before or after a dose of orlistat. • Do not take more of this medication than has been prescribed for you. Doses greater than 120 mg three times a day have not been shown to provide any additional weight-loss benefit. What is orlistat? • Orlistat blocks some of the fat that you eat from being absorbed by your body. • Orlistat is used in the management of obesity including weight loss and weight maintenance when used with a reduced-calorie diet. • Orlistat may also be used for purposes other than those listed in this medication guide. What should I discuss with my healthcare provider before taking orlistat? • Do not take orlistat without first talking to your doctor if you have · chronic malabsorption syndrome (an inability to absorb food and nutrients properly), or · gallbladder problems. • You may not be able to take orlistat if you have any of the conditions listed above. • Before taking orlistat, talk to your doctor if you · have a history of kidney stones, · have diabetes, · have anorexia or bulimia, · take any other weight-loss medicine, or · take cyclosporine (Sandimmune, Neoral). • You may not be able to take orlistat, or you may require a dosage adjustment or special monitoring during your treatment if you have any of the conditions listed above. • Orlistat is in the FDA pregnancy category B. This means that it is not expected to harm an unborn baby. Do not take orlistat without first talking to your doctor if you are pregnant. • It is not known whether orlistat passes into breast milk. Do not take orlistat without first talking to your doctor if you are breast-feeding a baby. How should I take orlistat? • Take orlistat exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you. • Take each dose with a full glass of water. • Orlistat is usually taken with each main meal that contains fat. Orlistat can be taken during meals or up to one hour after a meal. • Each time you take orlistat, your meal should contain no more than about 30% of calories from fat. Evenly divide your daily intake of fat, carbohydrates, and protein over three main meals a day. Talk to your doctor about following a healthy eating plan. • If you miss a meal, or if you have a meal without fat, you can skip your dose of orlistat for that meal also. • If orlistat is taken with any one meal that is very high in fat, there is an increased chance of digestive side effects. • Do not take more of this medication than has been prescribed for you. Doses greater than 120 mg three times a day have not been shown to provide an additional weight-loss benefit. • Orlistat may decrease your body's absorption of some fat-soluble vitamins. To ensure adequate nutrition, your doctor may recommend taking a multivitamin that contains vitamins D, E, K, and beta-carotene. Take your vitamin supplement once a day, at least 2 hours before or after a dose of orlistat. • Store orlistat at room temperature away from moisture and heat. What happens if I miss a dose? • Take the missed dose up to one hour after a meal. If more than one hour has passed since your last meal, skip the dose you missed and take only your next regularly scheduled dose as directed. Do not take a double dose of this medication. • If you miss a meal, or if you have a meal without fat, you can skip your dose of orlistat for that meal also. What happens if I overdose? • Seek emergency medical attention. • Symptoms of an orlistat overdose are not known. What should I avoid while taking orlistat? • Each time you take orlistat, your meal should contain no more than about 30% of calories from fat. Evenly divide your daily intake of fat, carbohydrates, and protein over three main meals a day. Talk to your doctor about following a healthy eating plan. What are the possible side effects of orlistat? • Stop taking orlistat and seek emergency medical attention if you experience a rare allergic reaction including shortness of breath; closing of your throat; swelling of your lips, tongue, or face; or hives. • Other, less serious side effects are more likely to occur. Continue to take orlistat and talk to your doctor if you experience · oily spotting; · oily or fatty stools; · orange or brown colored oil in your stool; · gas with discharge, an oily discharge; · an urgent need to go to the bathroom; · an inability to control bowel movements, or; · an increased number of bowel movements. • The bowel changes listed above are a natural effect of blocking fat and indicate that orlistat is working. They generally occur early in treatment, particularly after meals containing higher amounts of fat than are recommended. These symptoms are usually temporary and lessen or disappear as you continue treatment and keep to your recommended diet of meals containing 30% fat. • Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. What other drugs will affect orlistat? • Do not take orlistat without first talking to your doctor if you are taking any of the following medicines: · cyclosporine (Neoral, Sandimmune), or · warfarin (Coumadin). • You may not be able to take orlistat, or you may require a dosage adjustment or special monitoring during your treatment if you are taking any of the medicines listed above. • Orlistat may decrease your body's absorption of some fat-soluble vitamins. To ensure adequate nutrition, your doctor may recommend taking a multivitamin that contains vitamins D, E, K, and beta-carotene. Take your vitamin supplement once a day, at least 2 hours before or after a dose of orlistat. • Drugs other than those listed here may also interact with orlistat. Talk to your doctor and pharmacist before taking or using any other prescription or over-the-counter medicines including vitamins, minerals, and herbal products. Xenical Capsules Manufacturer: Roche Laboratories DESCRIPTION XENICAL (orlistat) is a lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats. Orlistat is (S)-2-formylamino-4-methyl-pentanoic acid (S)-1-[[(2S, 3S)-3-hexyl-4-oxo-2-oxetanyl] methyl]-dodecyl ester. Its empirical formula is C 29 H 53 NO 5 , and its molecular weight is 495.7. It is a single diastereomeric molecule that contains four chiral centers, with a negative optical rotation in ethanol at 529 nm. Orlistat is a white to off-white crystalline powder. Orlistat is practically insoluble in water, freely soluble in chloroform, and very soluble in methanol and ethanol. Orlistat has no p K a within the physiological pH range. XENICAL is available for oral administration in dark-blue, hard-gelatin capsules, with light-blue imprinting. Each capsule contains 120 mg of the active ingredient, orlistat. The capsules also contain the inactive ingredients microcrystalline cellulose, sodium starch glycolate, sodium lauryl sulfate, povidone, and talc. Each capsule shell contains gelatin, titanium dioxide, and FD&C Blue No.1, with printing of pharmaceutical glaze NF, titanium dioxide, and FD&C Blue No.1 aluminum lake. CLINICAL PHARMACOLOGY Mechanism of Action Orlistat is a reversible inhibitor of lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine residue site of gastric and pancreatic lipases. The inactivated enzymes are thus unavailable to hydrolyze dietary fat in the form of triglycerides into absorbable free fatty acids and monoglycerides. As undigested triglycerides are not absorbed, the resulting caloric deficit may have a positive effect on weight control. Systemic absorption of the drug is therefore not needed for activity. At the recommended therapeutic dose of 120 mg three times a day, orlistat inhibits dietary fat absorption by approximately 30%. Pharmacokinetics Absorption Systemic exposure to orlistat is minimal. Following oral dosing with 360 mg 14 C-orlistat, plasma radioactivity peaked at approximately 8 hours; plasma concentrations of intact orlistat were near the limits of detection (<5 ng/mL). In therapeutic studies involving monitoring of plasma samples, detection of intact orlistat in plasma was sporadic and concentrations were low (<10 ng/mL or 0.02 [micro ]M), without evidence of accumulation, and consistent with minimal absorption. The average absolute bioavailability of intact orlistat was assessed in studies with male rats at oral doses of 150 and 1000 mg/kg/day and in male dogs at oral doses of 100 and 1000 mg/kg/day and found to be 0.12%, 0.59% in rats and 0.7%, 1.9% in dogs, respectively. Distribution In vitro orlistat was >99% bound to plasma proteins (lipoproteins and albumin were major binding proteins). Orlistat minimally partitioned into erythrocytes. Metabolism Based on animal data, it is likely that the metabolism of orlistat occurs mainly within the gastrointestinal wall. Based on an oral 14 C-orlistat mass balance study in obese patients, two metabolites, M1 (4-member lactone ring hydrolyzed) and M3 (M1 with N-formyl leucine moiety cleaved), accounted for approximately 42% of total radioactivity in plasma. M1 and M3 have an open (beta)-lactone ring and extremely weak lipase inhibitory activity (1000- and 2500-fold less than orlistat, respectively). In view of this low inhibitory activity and the low plasma levels at the therapeutic dose (average of 26 ng/mL and 108 ng/mL for M1 and M3, respectively, 2 to 4 hours after a dose), these metabolites are considered pharmacologically inconsequential. The primary metabolite M1 had a short half-life (approximately 3 hours) whereas the secondary metabolite M3 disappeared at a slower rate (half-life approximately 13.5 hours). In obese patients, steady-state plasma levels of M1, but not M3, increased in proportion to orlistat doses. Elimination Following a single oral dose of 360 mg 14 C-orlistat in both normal weight and obese subjects, fecal excretion of the unabsorbed drug was found to be the major route of elimination. Orlistat and its M1 and M3 metabolites were also subject to biliary excretion. Approximately 97% of the administered radioactivity was excreted in feces; 83% of that was found to be unchanged orlistat. The cumulative renal excretion of total radioactivity was <2% of the given dose of 360 mg 14 C-orlistat. The time to reach complete excretion (fecal plus urinary) was 3 to 5 days. The disposition of orlistat appeared to be similar between normal weight and obese subjects. Based on limited data, the half-life of the absorbed orlistat is in the range of 1 to 2 hours. Special Populations Because the drug is minimally absorbed, studies in special populations (geriatric, different races, patients with renal and hepatic insufficiency) were not conducted. Pediatrics Plasma concentrations of orlistat and its metabolites M1 and M3 were similar to those found in adults at the same dose level. Daily fecal fat excretions were 27% and 7% of dietary intake in orlistat and placebo treatment groups, respectively. Drug-Drug Interactions Drug-drug interaction studies indicate that XENICAL had no effect on pharmacokinetics and/or pharmacodynamics of alcohol, digoxin, glyburide, nifedipine (extended-release tablets), oral contraceptives, phenytoin, pravastatin, or warfarin. Alcohol did not affect the pharmacodynamics of orlistat. Other Short-term Studies Adults In several studies of up to 6-weeks duration, the effects of therapeutic doses of XENICAL on gastrointestinal and systemic physiological processes were assessed in normal-weight and obese subjects. Postprandial cholecystokinin plasma concentrations were lowered after multiple doses of XENICAL in two studies but not significantly different from placebo in two other experiments. There were no clinically significant changes observed in gallbladder motility, bile composition or lithogenicity, or colonic cell proliferation rate, and no clinically significant reduction of gastric emptying time or gastric acidity. In addition, no effects on plasma triglyceride levels or systemic lipases were observed with the administration of XENICAL in these studies. In a 3-week study of 28 healthy male volunteers, XENICAL (120 mg three times a day) did not significantly affect the balance of calcium, magnesium, phosphorus, zinc, copper, and iron. Pediatrics In a 3-week study of 32 obese adolescents aged 12 to 16 years, XENICAL (120 mg three times a day) did not significantly affect the balance of calcium, magnesium, phosphorus, zinc, or copper. The iron balance was decreased by 64.7 [micro ]mole/24 hours and 40.4 [micro ]mole/24 hours in orlistat and placebo treatment groups, respectively. Dose-response Relationship A simple maximum effect (E max ) model was used to define the dose-response curve of the relationship between XENICAL daily dose and fecal fat excretion as representative of gastrointestinal lipase inhibition. The dose-response curve demonstrated a steep portion for doses up to approximately 400 mg daily, followed by a plateau for higher doses. At doses greater than 120 mg three times a day, the percentage increase in effect was minimal. CLINICAL STUDIES Observational epidemiologic studies have established a relationship between obesity and visceral fat and the risks for cardiovascular disease, type 2 diabetes, certain forms of cancer, gallstones, certain respiratory disorders, and an increase in overall mortality. These studies suggest that weight loss, if maintained, may produce health benefits for obese patients who have or are at risk of developing weight-related comorbidities. The long-term effects of orlistat on morbidity and mortality associated with obesity have not been established. 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 seven long-term (1- to 2-years duration) multicenter, double-blind, placebo-controlled clinical trials. During the first year of therapy, the studies of 2-year duration assessed weight loss and weight maintenance. During the second year of therapy, some studies assessed continued weight loss and weight maintenance and others assessed the effect of orlistat on weight regain. These studies included over 2800 patients treated with XENICAL and 1400 patients treated with placebo. The majority of these patients had obesity-related risk factors and comorbidities. In the XENDOS study, which included 3304 patients, the time to onset of type 2 diabetes was assessed in addition to weight management. In all these studies, treatment with XENICAL and placebo designates treatment with XENICAL plus diet and placebo plus diet, respectively. During the weight loss and weight maintenance period, a well-balanced, reduced-calorie diet that was intended to result in an approximate 20% decrease in caloric intake and provide 30% of calories from fat was recommended to all patients. In addition, all patients were offered nutritional counseling. One-year Results: Weight Loss, Weight Maintenance, and Risk Factors Weight loss was observed within 2 weeks of initiation of therapy and continued for 6 to 12 months. Pooled data from five clinical trials indicated that the overall mean weight loss from randomization to the end of 6 months and 1 year of treatment in the intent-to-treat population were 12.4 lbs and 13.4 lbs in the patients treated with XENICAL and 6.2 lbs and 5.8 lbs in the placebo-treated patients, respectively. During the 4-week placebo lead-in period of the studies, an additional 5 to 6 lb weight loss was also observed in the same patients. Of the patients who completed 1 year of treatment, 57% of the patients treated with XENICAL (120 mg three times a day) and 31% of the placebo-treated patients lost at least 5% of their baseline body weight. The percentages of patients achieving >/=5% and >/=10% weight loss after 1 year in five large multicenter studies for the intent-to-treat populations are presented in Table 1. Table 1 Percentage of Patients Losing >/=5% and >/=10% of Body Weight From Randomization After 1-Year Treatment * Intent-to-Treat Population **/* >/=5% Weight Loss >/=10% Weight Loss Study No. XENICAL n Placebo n p-value XENICAL n Placebo n p-value 14119B 35.5% 110 21.3% 108 0.021 16.4% 110 6.5% 108 0.022 14119C 54.8% 343 27.4% 340 <0.001 24.8% 343 8.2% 340 <0.001 14149 50.6% 241 26.3% 236 <0.001 22.8% 241 11.9% 236 0.02 14161 **/** 37.1% 210 16.0% 212 <0.001 19.5% 210 3.8% 212 <0.001 14185 42.6% 657 22.4% 223 <0.001 17.7% 657 9.9% 223 0.006 The diet utilized during year 1 was a reduced-calorie diet. * Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet **/* Last observation carried forward **/** All studies, with the exception of 14161, were conducted at centers specialized in treating obesity and complications of obesity. Study 14161 was conducted with primary care physicians. The relative changes in risk factors associated with obesity following 1 year of therapy with XENICAL and placebo are presented for the population as a whole and for the population with abnormal values at randomization. Population as a Whole The changes in metabolic, cardiovascular and anthropometric risk factors associated with obesity based on pooled data for five clinical studies, regardless of the patient's risk factor status at randomization, are presented in Table 2. One year of therapy with XENICAL resulted in relative improvement in several risk factors. Table 2 Mean Change in Risk Factors From Randomization Following 1-Year Treatment * Population as a Whole Risk Factor XENICAL 120 mg **/* Placebo **/* Metabolic: Total Cholesterol -2.0% +5.0% LDL-Cholesterol -4.0% +5.0% HDL-Cholesterol +9.3% +12.8% LDL/HDL -0.3 -0.20 Triglycerides +1.34% +2.9% Fasting Glucose, mmol/L -0.04 +0.0 Fasting Insulin, pmol/L -6.7 +5.2 Cardiovascular: Systolic Blood Pressure, mm Hg -1.01 +0.58 Diastolic Blood Pressure, mm Hg -1.19 +0.46 Anthropometric: Waist Circumference, cm -6.45 -4.04 Hip Circumference, cm -5.31 -2.96 * Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet **/* Intent-to-treat population at week 52, observed data based on pooled data from 5 studies Population With Abnormal Risk Factors at Randomization The changes from randomization following 1-year treatment in the population with abnormal lipid levels (LDL >/=130 mg/dL, LDL/HDL >/=3.5, HDL <35 mg/dL) were greater for XENICAL compared to placebo with respect to LDL-cholesterol (-7.83% vs +1.14%) and the LDL/HDL ratio (-0.64 vs -0.46). HDL increased in the placebo group by 20.1% and in the XENICAL group by 18.8%. In the population with abnormal blood pressure at baseline (systolic BP >/=140 mm Hg), the change in SBP from randomization to 1 year was greater for XENICAL (-10.89 mm Hg) than placebo (-5.07 mm Hg). For patients with a diastolic blood pressure >/=90 mm Hg, XENICAL patients decreased by -7.9 mm Hg while the placebo patients decreased by -5.5 mm Hg. Fasting insulin decreased more for XENICAL than placebo (-39 vs -16 pmol/L) from randomization to 1 year in the population with abnormal baseline values (>/=120 pmol/L). A greater reduction in waist circumference for XENICAL vs placebo (-7.29 vs -4.53 cm) was observed in the population with abnormal baseline values (>/=100 cm). Effect on Weight Regain Three studies were designed to evaluate the effects of XENICAL compared to placebo in reducing weight regain after a previous weight loss achieved following either diet alone (one study, 14302) or prior treatment with XENICAL (two studies, 14119C and 14185). The diet utilized during the 1-year weight regain portion of the studies was a weight-maintenance diet, rather than a weight-loss diet, and patients received less nutritional counseling than patients in weight-loss studies. For studies 14119C and 14185, patients' previous weight loss was due to 1 year of treatment with XENICAL in conjunction with a mildly hypocaloric diet. Study 14302 was conducted to evaluate the effects of 1 year of treatment with XENICAL on weight regain in patients who had lost 8% or more of their body weight in the previous 6 months on diet alone. In 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<0.001). In 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<0.001). In 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<0.001). 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 previously discussed (see Table 1). At the end of year 1, the patients' diets were reviewed and changed where necessary. The diet prescribed in the second year was designed to maintain patient's current weight. XENICAL was shown to be more effective than placebo in long-term weight control in four large, multicenter, 2-year double-blind, placebo-controlled studies. Pooled data from four clinical studies indicate that 40% of all patients treated with 120 mg three times a day of XENICAL and 24% of patients treated with placebo who completed 2 years of the same therapy had >/=5% loss of body weight from randomization. Pooled data from four clinical studies indicate that the relative weight loss advantage between XENICAL 120 mg three times a day and placebo treatment groups was the same after 2 years as for 1 year, indicating that the pharmacologic advantage of XENICAL was maintained over 2 years. In the same studies cited in the One-year Results (see Table 1), the percentages of patients achieving a >/=5% and >/=10% weight loss after 2 years are shown in Table 3. Table 3 Percentage of Patients Losing >/=5% and >/=10% of Body Weight From Randomization After 2-Year Treatment * Intent-to-Treat Population **/* >/=5% Weight Loss >/=10% Weight Loss Study No. XENICAL n Placebo n p-value XENICAL n Placebo n p-value 14119C 45.1% 133 23.6% 123 <0.001 24.8% 133 6.5% 123 <0.001 14149 43.3% 178 27.2% 158 0.002 18.0% 178 9.5% 158 0.025 14161 **/** 25.0% 148 15.0% 113 0.049 16.9% 148 3.5% 113 0.001 14185 34.0% 147 27.9% 122 0.279 17.7% 147 11.5% 122 0.154 The diet utilized during year 2 was designed for weight maintenance and not weight loss. * Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet **/* Last observation carried forward **/** All studies, with the exception of 14161 were conducted at centers specializing in treating obesity or complications of obesity. Study 14161 was conducted with primary care physicians. The relative changes in risk factors associated with obesity following 2 years of therapy were also assessed in the population as a whole and the population with abnormal risk factors at randomization. Population as a Whole 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 one results. Population With Abnormal Risk Factors at Randomization The relative differences in risk factors between treatment with XENICAL and placebo were similar to the results following 1 year of therapy for LDL- and HDL-cholesterol, triglycerides, fasting insulin, diastolic blood pressure, and waist circumference. The relative differences between treatment groups for LDL/HDL ratio and isolated systolic blood pressure were less than that observed in the year one results. Four-Year Results: Long-term Weight Control and Risk Factors In the 4-year double-blind, placebo-controlled XENDOS study, the effects of orlistat in delaying the onset of type 2 diabetes and on body weight were compared to placebo in 3304 obese patients who had either normal or impaired glucose tolerance at baseline. Thirty-four percent of the 1655 patients who were randomized to the placebo group and 52% of the 1649 patients who were randomized to the orlistat group completed the 4-year study. At the end of the study, the mean percent weight loss in the placebo group was -2.75% compared with -5.17% in the orlistat group (p<0.001) (see Figure 1). Forty-five percent of the placebo patients and 73% of the orlistat patients lost >/=5% of their baseline body weight, and 21% of the placebo patients and 41% of the orlistat patients lost >/=10% of their baseline body weight following the first year of treatment. Following 4 years of treatment, 28% of the placebo patients and 45% of the orlistat patients lost >/=5% of their baseline body weight and 10% of the placebo patients and 21% of the orlistat patients lost >/=10% of their baseline body weight. The relative changes from baseline in risk factors associated with obesity following 4 years of therapy were assessed in the XENDOS study population (see Table 4). Table 4 Mean Change in Risk Factors From Randomization Following 4-Years Treatment * Risk Factor XENICAL 120 mg **/* Placebo **/* Metabolic: Total Cholesterol -7.02% -2.03% LDL-Cholesterol -11.66% -3.85% HDL-Cholesterol +5.92% +7.01% LDL/HDL -0.53 -0.33 Triglycerides +3.64% +1.30 Fasting Glucose, mmol/L +0.12 +0.23 Fasting Insulin, pmol/L -24.93 -15.71 Cardiovascular: Systolic Blood Pressure, mm Hg -4.12 -2.60 Diastolic Blood Pressure, mm Hg -1.93 -0.87 Anthropometric: Waist Circumference, cm -5.78 -3.99 *Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet **/* Intent-to-treat population Study of Patients With Type 2 Diabetes 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 to 13% of the placebo-treated patients (p<0.001). Table 5 describes the changes over 1 year of treatment with XENICAL compared to placebo, in sulfonylurea usage and dose reduction as well as in hemoglobin HbA1c, fasting glucose, and insulin. Mean Changes in Body Weight and Glycemic Control From Randomization Following 1-Year Treatment in Patients With Type 2 Diabetes XENICAL 120 mg * (n=162) Placebo * (n=159) Statistical Significance % patients who discontinued dose of oral sulfonylurea 11.7% 7.5% **/* % patients who decreased dose of oral sulfonylurea 31.5% 21.4% Average reduction in sulfonylurea medication dose -22.8% -9.1% **/* Body weight change (lbs) -8.9 -4.2 **/* HbA1c -0.18% +0.28% **/* Fasting glucose, mmol/L -0.02 +0.54 **/* Fasting insulin, pmol/L -19.68 -18.02 ns Statistical significance based on intent-to-treat population, last observation carried forward. * Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet **/* Statistically significant (p 0.05 In addition, XENICAL (n=162) compared to placebo (n=159) was associated with significant lowering for total cholesterol (-1.0% vs +9.0%, p0.05. Systolic blood pressure increased by +0.61 mm Hg on XENICAL and increased by +4.33 mm Hg on placebo, p>0.05. Diastolic blood pressure decreased by -0.47 mm Hg for XENICAL and by -0.5 mm Hg for placebo, p>0.05. Glucose Tolerance in Obese Patients Two-year studies that included oral glucose tolerance tests were conducted in obese patients not previously diagnosed or treated for type 2 diabetes and whose baseline oral glucose tolerance test (OGTT) status at randomization was either normal, impaired, or diabetic. The progression from a normal OGTT at randomiza