Active ingredients: Orlistat
Alli 60 mg hard capsules
Alli package inserts are available for pack sizes:- Alli 60 mg hard capsules
- Alli 27 mg chewable tablets
Why is Alli used? What is it for?
alli is used for weight loss in adults aged 18 and over who are overweight, with a body mass index (BMI) of 28 or greater. alli should be used in conjunction with a reduced calorie diet and reduced fat content.
BMI is a way to gauge if your weight is right or if you are overweight for your height. The table below will help you find out if you are overweight and if alli is right for you.
Look for its height in the table. If your weight is less than indicated for your height, do not take alli.
Reskins associated with being overweight
Being overweight increases the risk of developing several serious health problems, such as diabetes and cardiovascular disease. These conditions may not cause you any obvious discomfort, so you should see your doctor for a general check of your health.
How does alli
The active ingredient in alli (orlistat) has been studied to act on fats in the digestive system. This substance blocks the absorption of about a quarter of the fats present in meals. These fats are then eliminated from the body in the stool. You may experience diet-related treatment effects. It is therefore important to commit to a reduced-fat diet to control these effects. In doing so, the effect of the capsules will support your commitment, helping you to lose more weight than dieting alone. For every 2kg you lose from dieting alone, alli can help you lose 1kg more.
Contraindications When Alli should not be used
Do not take alli
- If you are allergic to orlistat or any of the other ingredients of this medicine
- If you are pregnant or breastfeeding.
- If you are taking cyclosporine, a medicine used after organ transplants, for severe rheumatoid arthritis and some severe skin conditions.
- If you are taking warfarin or other medicines used to thin the blood.
- If you have cholestasis (a condition in which the flow of bile from the liver is blocked).
- If you have food absorption problems (chronic malabsorption syndrome) diagnosed by a doctor.
Precautions for use What you need to know before taking Alli
Talk to your doctor or pharmacist before taking alli
If you have diabetes, please tell your doctor that you may need to adjust the dose of your anti-diabetic medicine.
If you have kidney disease. Consult your doctor before taking alli if you have kidney problems. The use of orlistat may be associated with the formation of kidney stones in patients suffering from chronic kidney disease.
Children and adolescents
This medicine should not be taken by children and adolescents under the age of 18.
Interactions Which drugs or foods can change the effect of Alli
alli may affect some medicines you need to take.
Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines. Do not take alli with these medicines
- Ciclosporin: Ciclosporin is used after organ transplants, for severe forms of rheumatoid arthritis and in some severe skin conditions.
- Warfarin or other medicines to thin the blood.
The oral contraceptive pill and alli
- The oral contraceptive pill may be less effective in case of severe diarrhea. Use an additional method of contraception if you develop severe diarrhea.
Multivitamin preparations and alli
- It is recommended to take a multivitamin preparation every day. alli can reduce the levels of some vitamins absorbed by the body. The multivitamin preparation must contain vitamins A, D, E and K. The multivitamin preparation must be taken before bedtime, at a time other than when taking alli, to promote the absorption of vitamins.
Tell your doctor before taking alli if you are taking
- amiodarone, used for heart rhythm problems.
- acarbose (an anti-diabetic medicine used to treat type 2 diabetes mellitus). alli is not recommended in people taking acarbose.
- a thyroid medicine (levothyroxine), as your dose may need to be adjusted and you may need to take the two medicines at different times of the day. - a medicine for epilepsy, as any changes in the frequency and intensity of seizures should be discussed with your doctor.
- medicines to treat HIV. It is important to consult your doctor before taking alli, if you are taking medicines for HIV.
Tell your doctor or pharmacist when you take alli
- if you are taking a medicine for high blood pressure, as your dose may need to be adjusted.
- if you are taking a high cholesterol medicine, as your dose may need to be adjusted.
alli with food and drink
alli should be taken in conjunction with a reduced calorie and reduced fat diet. Try starting the diet before starting treatment. For information on how to set your calorie and fat goals, read the Other Useful Information section
alli can be taken just before, during or within one hour after a meal. The capsule should be swallowed with water. This generally means one capsule with breakfast, lunch and dinner. If you miss a meal or eat a meal that does not contain fat , do not take the capsule. alli will not work if the meal does not contain at least some fat.
If you have a high-fat meal, do not take more than the recommended dose. Taking the capsule with a meal containing too much fat may increase the chances of developing diet-related treatment effects. Make every effort to avoid any meal containing a lot of fat while taking alli.
Warnings It is important to know that:
Pregnancy and breastfeeding
Do not take alli if you are pregnant or breastfeeding.
Driving and using machines
Alli is unlikely to affect your ability to drive or use machines.
Dose, Method and Time of Administration How to use Alli: Posology
Prepare to lose weight
1. Choose a start date
Choose the date you will start taking the capsules in advance. Before you start taking the capsules, start the reduced calorie and fat diet and give your body a few days to get used to your new eating habits. Record what you eat in a food diary. These journals are effective because they make her aware of what she eats and how much she eats, giving her the basis for making changes.
2. Decide on your weight loss goal
Think about how many pounds you want to lose and then set a weight goal. A realistic goal is to lose between 5% and 10% of your starting weight. The amount of weight you can lose can vary from week to week. You must aim to lose weight at a gradual and steady rate of about 0.5 kg per week.
3. Set your calorie and fat goals
To help you reach your weight goal, you need to set two daily goals, one for calories and one for fat. For more advice, read the section Other useful information
Taking alli
Adults aged 18 and over
- Take one capsule, three times a day.
- Take alli immediately before, during or within one "hour of meals. This generally means one capsule for breakfast, one for lunch and one for dinner. Make sure your three main meals are well balanced, and low in calories and fat."
- If you miss a meal, or if you eat a meal that does not contain fat, do not take the capsule. alli does not work if the meal does not contain at least some fat.
- Swallow the capsule whole with some water.
- Do not take more than 3 capsules per day.
- You can keep your daily dose of alli in the blue portable case (shuttle) contained in this pack.
- Eat reduced-fat meals to decrease your chances of developing diet-related treatment effects
- Try to be more physically active before starting treatment with the capsules. Physical activity is an important part of a weight loss program. If you have never done any physical activity, remember to check with your doctor first.
- Keep exercising while taking alli and even after you stop taking it.
How long should you take alli
- alli should not be taken for more than six months.
- If you do not lose weight after taking alli for 12 weeks, ask your doctor or pharmacist for advice. You may need to suspend alli.
- Effective weight loss is not only achieved by eating differently for a short period of time and then returning to old eating habits. People who lose weight and maintain the weight change their lifestyles by changing what they eat and how level of physical activity.
Overdose What to do if you have taken too much Alli
If you take more alli than you should
Do not take more than 3 capsules per day.
- If you have taken too many capsules, contact your doctor immediately.
If you forget to take alli
If you have forgotten to take a capsule:
- If it has been less than an "hour since" your last meal, take the forgotten capsule.
- If it has been more than one "hour since" your last meal, do not take the forgotten capsule. Wait and take the next capsule around your next meal as usual
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Alli
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most of the side effects of alli (for example, gas with or without oily discharge, sudden or more frequent bowel movements, and soft stools) are caused by the way it works. these diet-associated treatment effects.
Serious side effects
It is not known how often these side effects occur.
Severe allergic reactions
- Signs of a severe allergic reaction include: severe breathing difficulties, sweating, erythema, itching, swelling of the face, rapid heartbeat, collapse.
- Stop taking the capsules. Get medical attention immediately.
Other serious side effects
- Anal bleeding.
- Diverticulitis (inflammation of the large intestine). Symptoms may include abdominal pain, especially on the left, possibly accompanied by fever and constipation.
- Pancreatitis (inflammation of the pancreas). Symptoms may include severe abdominal pain sometimes radiating to the back, possibly accompanied by fever, nausea and vomiting.
- Blisters on the skin (including blisters that burst).
- Severe abdominal pain caused by gallstones.
- Hepatitis (inflammation of the liver). Symptoms may include yellowing of the skin and eyes, itching, dark colored urine, abdominal pain and aching liver (indicated by pain under the front of the rib cage on the right side), sometimes with loss of appetite.
- Oxalate nephropathy (accumulation of calcium oxalate which can lead to the formation of kidney stones). See section warnings and precautions.
Stop taking the capsules. If you experience any of these, please tell your doctor.
Very common side effects
They may affect more than 1 in 10 people who take alli
- Presence of intestinal gas, with or without oily losses
- Sudden intestinal discharges
- Fatty or oily stools
- Soft stools
Tell your doctor or pharmacist if any of these effects become serious or troubling.
Common side effects
They can affect up to 1 in 10 people who take alli
- Abdominal pain
- Faecal incontinence
- Liquid stools
- More frequent intestinal discharges
Anxiety
Tell your doctor or pharmacist if any of these effects become serious or troubling.
Effects seen in blood tests
It is not known how often these effects occur
- Increase in the levels of some liver enzymes.
- Effects on blood clotting in people treated with warfarin or other blood-thinning medicines (anticoagulants).
Tell your doctor that you are taking alli if you have blood tests.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Learn to manage the effects of treatment associated with diet
Most of the side effects are caused by the way the capsules work and result from the fact that some of the fats pass through the body and are excreted as such in the stool. These effects typically occur within the first few weeks of treatment, before getting used to limiting the amount of fat in the diet. These diet-associated treatment effects may be a sign that you have eaten more fat than you should have. You can learn how to minimize the impact of diet-related treatment effects by observing these rules:
- Start on a reduced fat diet for a few days, or even a week, before you start taking the capsules.
- Be more aware of how much fat your favorite foods contain and the portion sizes you eat. By becoming familiar with portions, you will be less likely to accidentally exceed your target amount of fat.
- Distribute your fat allowance evenly over the different meals of the day. You don't save fat and calories and indulge in a high-fat meal or dessert like you might with other weight loss programs.
- Most people who experienced these effects found them manageable and controllable by adjusting their diet.
Don't worry if you don't have any of these problems. This does not mean that the capsules do not work.
Expiry and Retention
- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the carton and bottle after "EXP". The expiry date refers to the last day of the month indicated.
- Do not store above 25 ° C.
- Keep the bottle tightly closed to protect the medicine from moisture.
- The bottle contains two sealed cylinders containing silica gel to keep the capsules dry. Keep the cylinders in the bottle. Do not ingest them.
- You can keep the daily dose of alli in the blue portable case (shuttle) contained in the package. Throw away the capsules stored for more than one month in the portable case.
- Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What does alli
The active ingredient is orlistat. Each hard capsule contains 60 mg of orlistat.
The other ingredients are:
- Capsule contents: microcrystalline cellulose (E460), sodium starch glycolate, povidone (E1201), sodium lauryl sulfate, talc.
- Capsule: gelatin, indigo carmine (E132), titanium dioxide (E171), sodium lauryl sulfate, sorbitan monolaurate, black ink (shellac, black iron oxide (E172), propylene glycol).
- Capsule band: gelatin, polysorbate 80, indigo carmine (E132).
Description of the appearance of alli and contents of the package
The alli capsules have a turquoise head and body, with a dark blue band in the center, embossed with "alli".
alli is available in packs of 42, 60, 84, 90 and 120 capsules. Not all packs may be available in all countries.
A blue portable pouch (shuttle) is contained in this pack to take your daily dose of alli with you.
OTHER USEFUL INFORMATION
Risks associated with being overweight
Being overweight affects your health and increases your risk of developing serious health problems such as:
- High pressure
- Diabetes
- Cardiovascular diseases
- Stroke
- Some forms of cancer
- Osteoarthritis
Talk to your doctor about your personal risks of developing such problems.
The importance of losing weight
Losing weight and maintaining weight loss, for example by improving diet and increasing physical activity, can help reduce the risk of major health problems and improve health.
Helpful advice on diet and calorie and fat goals while taking alli
alli should be used in conjunction with a reduced calorie and reduced fat diet. The capsules work by preventing the absorption of some of the fat ingested from the diet, but you can continue to eat foods of all the main food groups. Even if you need to focus on the calories and fats you eat, it is important to follow a diet. It makes sense to choose meals that contain a variety of different nutrients and learn how to eat properly over the long term.
Understand the importance of fat and calorie goals
Calories are a measure of the energy required by the body. Sometimes they are called kilocalories or kcal. Energy can also be measured in kilojoules, which can also be found on food labels.
- Your calorie goal is the maximum number of calories you can take in a day. See the table later in this section.
- The gram of fat goal is the maximum number of grams of fat you can eat at each meal. The fat table is shown after the information below on setting a calorie goal.
- Keeping your fat goal under control is key, considering how the capsules work. By taking alli, your body will eliminate more fat, and therefore may find it difficult to manage it if you eat the same amount of fat as before. Therefore, by respecting the predefined fat goal, you will be able to obtain the maximum results in terms of weight loss, minimizing the risk of undesirable effects of the treatment associated with the diet.
- He will have to try to lose weight gradually and steadily. The ideal is to lose about 0.5 kg per week.
How to set the calorie goal
The table below has been designed to give you a lower calorie goal of around 500 calories per day than your body requires to maintain your current weight. In total, this is 3500 calories less per week, which is the amount of calories contained in 0.5 kg of fat.
Only by meeting the calorie goal, you should be able to lose weight at a gradual and steady rate of about 0.5 kg per week, without feeling frustrated or dissatisfied.
It is not recommended to consume less than 1200 calories per day.
To set your calorie goal, you need to know your activity level.
The more active you are, the higher your calorie goal will be.
- A low level of activity means practicing little or no activities such as walking, climbing stairs, gardening, or other daily physical activities.
- A moderate level of activity means you burn about 150 calories a day in physical activity, for example, walking three kilometers, gardening for 30-45 minutes, or running two kilometers in 15 minutes. Choose the activity level that best suits your daily habits. If you are unsure of your level, choose a low activity level.
Women
Men
How to set the goal in terms of fat
The table below shows you how to set your fat goal based on the amount of daily calories you can allow. He will have to plan on consuming 3 meals a day. For example, if you set a calorie goal of 1400 calories per day, the maximum amount of fat allowed for each meal will be 15g. To respect the allowed amount of daily fat, snacks should not contain more than 3 g of fat.
Memories
- Set a realistic calorie and fat goal, as this is a good way to maintain your weight goals over the long term.
- Write down what you eat in a food diary, including calorie and fat content.
- Try to increase your level of physical activity before you start taking the capsules. Physical activity is an important part of a weight loss program. If you have never exercised before, remember to consult your doctor.
- You continue to stay active while taking alli and after stopping treatment.
The alli weight loss program combines the capsules with a diet plan and a wide range of resources to help you understand how to follow a reduced calorie and fat diet, as well as guidelines for becoming more active.
The alli website (refer to your country specific website included in the list of local representatives above) provides you with a range of interactive tools, reduced fat recipes, exercise tips and other useful information. to help you lead a healthy life and to support you in pursuing your weight reduction goals, as well as details of a tailor-made weight loss program.
Visit www.alli.it
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ALLI 60 MG HARD CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each hard capsule contains 60 mg of orlistat.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsule
The capsule has a central dark blue band, and a turquoise colored head and body marked with "alli".
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
alli is indicated for weight loss in overweight adults (body mass index, BMI, ≥ 28 kg / m2) and should be taken in conjunction with a moderately low-calorie, reduced-fat diet.
04.2 Posology and method of administration
Dosage
Adults
The recommended dosage of alli is one 60 mg capsule to be taken three times a day. No more than three 60 mg capsules should be taken in any 24 hours.
Diet and exercise are important components of a weight loss program. It is recommended that you start a diet and exercise program before starting treatment with alli.
During treatment with orlistat, the patient should follow a nutritionally balanced and moderately low-calorie diet, which contains approximately 30% of calories from fat (e.g. in a 2,000 kcal per day diet, this is equivalent to a quantitative carbohydrates and proteins must be distributed over the three main meals.
The diet and exercise program should continue even when alli treatment is stopped.
Treatment should not exceed 6 months.
Patients who are unable to lose weight after 12 weeks of treatment with alli should consult their doctor or pharmacist. Treatment may need to be stopped.
Special populations
Elderly (> 65 years)
Only limited data are available on the use of orlistat in the elderly. However, since orlistat is only minimally absorbed, no dose adjustment is required in the elderly.
Hepatic and renal insufficiency
The effects of orlistat in subjects with hepatic and / or renal insufficiency have not been studied.
However, as orlistat is only minimally absorbed, no dose adjustment is required in subjects with hepatic and / or renal insufficiency.
Pediatric population
The safety and efficacy of alli in children aged below 18 years have not been established. No data are available.
Method of administration
The capsule should be taken immediately before, during or within one hour after the main meals. If a meal is skipped or if it does not contain fat, the orlistat dose should be omitted.
04.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients
• Concomitant treatment with cyclosporine (see section 4.5)
• Chronic malabsorption syndrome
• Cholestasis
• Pregnancy (see section 4.6)
• Breastfeeding (see section 4.6)
• Concomitant treatment with warfarin or other oral anticoagulants (see sections 4.5 and 4.8)
04.4 Special warnings and appropriate precautions for use
Patients should be advised to adhere to received dietary recommendations (see section 4.2). The possibility of developing gastrointestinal symptoms (see section 4.8) may be increased if orlistat is taken with a single meal or a high-fat diet.
Treatment with orlistat may impair the absorption of fat-soluble vitamins (A, D, E and K) (see section 4.5). For this reason, a multivitamin supplement should be taken before bedtime.
Because weight loss may be associated with improved metabolic control of diabetes, patients taking a diabetes medicine should consult with their doctor before starting treatment with alli, should it become necessary to adjust the dose of the antidiabetic drug.
Weight loss can be associated with an improvement in blood pressure and cholesterol levels. Patients taking a medicine for hypertension or hypercholesterolaemia should consult their doctor or pharmacist during treatment with alli if it becomes necessary to adjust the dose of these medicines.
Patients taking amiodarone should consult their physician before starting treatment with alli (see section 4.5).
There have been reports of rectal bleeding in patients taking orlistat. Should this occur, the patient should consult a physician.
The use of an additional contraceptive method is recommended to prevent the possible failure of oral contraceptives which could occur in case of severe diarrhea (see section 4.5).
Patients with nephropathy should consult their physician before starting treatment with alli, as the use of orlistat may rarely be associated with hyperoxaluria and oxalate nephropathy.
Hypothyroidism and / or reduced control of hypothyroidism may occur when orlistat and levothyroxine are taken at the same time (see section 4.5). Patients taking levothyroxine should consult their physician before starting treatment with alli, as orlistat may need to be taken and levothyroxine at different times and adjust the levothyroxine dose.
Patients taking an anti-epileptic drug should consult their physician before starting treatment with alli, as such individuals should be monitored for any changes in the frequency and intensity of seizures. If this occurs, consideration should be given to the possibility of administering orlistat and anti-epileptic drugs at different times (see section 4.5).
04.5 Interactions with other medicinal products and other forms of interaction
Cyclosporine
A decrease in plasma levels of cyclosporine was observed in a drug interaction study and was also reported in many cases of concomitant administration with orlistat. This could lead to a decrease in the immunosuppressive efficacy of cyclosporine. Concomitant use of alli and cyclosporine is therefore contraindicated (see section 4.3).
Oral anticoagulants
Administration of warfarin or other oral anticoagulants concomitantly with orlistat may affect the international normalized ratio values (International Normalized Ratio INR) (see section 4.8). Concomitant use of alli and warfarin or other oral anticoagulants is therefore contraindicated (see section 4.3).
Oral contraceptives
The absence of an interaction between oral contraceptives and orlistat has been demonstrated in specific drug interaction studies. However, orlistat may indirectly reduce the availability of oral contraceptives and lead, in some individual cases, to unwanted pregnancy. additional contraceptive method in case of severe diarrhea (see section 4.4).
Levothyroxine
Hypothyroidism and / or reduced control of hypothyroidism may occur when orlistat and levothyroxine are taken simultaneously (see section 4.4). These effects may be due to reduced absorption of iodine salts and / or levothyroxine.
Anti-epileptic drugs
Cases of seizures have been reported in patients treated concomitantly with orlistat and anti-epileptic drugs, such as e.g. valproate, lamotrigine; for such cases a causal relationship due to an interaction cannot be excluded. Orlistat may decrease the absorption of anti-epileptic drugs, leading to convulsions.
Fat-soluble vitamins
Orlistat therapy has the potential to reduce the absorption of fat-soluble vitamins (A, D, E and K).
In clinical studies, plasma levels of vitamins A, D, E and K, and beta-carotene were maintained within the normal range in a "large majority of subjects receiving orlistat therapy for up to 4 years. However, they should be invited. patients to take a multivitamin supplement at bedtime to help ensure adequate vitamin intake (see section 4.4).
Acarbose
In the absence of pharmacokinetic interaction studies, alli is not recommended in patients treated with acarbose.
Amiodarone
A decrease in plasma levels of amiodarone, given as a single dose, was observed in a limited number of healthy volunteers treated concomitantly with orlistat. The clinical relevance of this effect in patients receiving amiodarone is still unknown. Patients taking amiodarone should consult their doctor before starting treatment with alli. Amiodarone dose adjustment may be required during treatment with alli.
04.6 Pregnancy and lactation
Women of childbearing potential / Contraception in men and women
The use of an additional contraceptive method is recommended to prevent the possible ineffectiveness of oral contraception in case of severe diarrhea (see sections 4.4 and 4.5).
Pregnancy
For orlistat, no clinical data on exposed pregnancies are available.Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development (see section 5.3).
alli is contraindicated in pregnancy (see section 4.3).
Feeding time
Since it is not known whether orlistat is excreted in human milk, alli is contraindicated during lactation (see section 4.3).
Fertility
Animal studies show no harmful effects on fertility.
04.7 Effects on ability to drive and use machines
Orlistat has no or negligible influence on the ability to drive or use machines.
04.8 Undesirable effects
Adverse reactions to orlistat are predominantly affecting the gastrointestinal tract and are related to the pharmacological effect of the drug on inhibition of ingested fat absorption.
Gastrointestinal adverse reactions identified in clinical studies with orlistat 60 mg lasting 18 months to 2 years were generally mild and transient. They generally occurred in phase
treatment (within 3 months) and most patients experienced only one episode. Consumption of a low fat diet tends to decrease the likelihood of developing gastrointestinal adverse reactions (see section 4.4).
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100,
The frequencies of adverse reactions identified during the post-marketing phase of orlistat are unknown as these reactions were reported voluntarily from a population of undefined size.
Within each frequency class, adverse reactions are reported in order of decreasing severity.
? It is plausible that treatment with orlistat may induce anticipatory anxiety or secondary to gastrointestinal adverse reactions.
04.9 Overdose
Single doses of 800 mg of orlistat and multiple doses of up to 400 mg three times daily for 15 days in normal weight and obese subjects were studied with no significant clinical evidence. In addition, doses of 240 mg three times a day were administered to obese patients for 6 months. The majority of post-marketing orlistat overdose cases reported no adverse reactions or reported adverse reactions similar to those reported with the recommended dose.
In the event of an overdose, medical attention should be sought. Should a significant overdose of orlistat occur, it is recommended that the patient be observed for 24 hours. Based on clinical and animal studies, any systemic effects attributable to orlistat's lipase inhibiting properties are expected to be rapidly reversible.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-obesity drugs, excluding dietetic products, peripherally acting anti-obesity drugs, ATC code A08AB01.
Orlistat is a potent, specific and long-acting inhibitor of gastrointestinal lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active site of the serine of the gastric and pancreatic lipases. The inactivated enzyme is therefore not available to hydrolyze the fat consumed to absorbable free fatty acids and monoglycerides. with the diet in the form of triglycerides. On the basis of clinical studies it has been estimated that orlistat 60 mg taken three times a day blocks the absorption of approximately 25% of dietary fat. The effect of orlistat results in an increase in fecal fat by as early as 24 to 48 hours after administration. After discontinuation of treatment, the fat content in the stool generally returns to pre-treatment levels within 48-72 hours.
Two double-blind, randomized, placebo-controlled studies conducted in adults with BMI
≥ 28 kg / m2 support the efficacy of orlistat 60 mg taken three times daily in combination with a low-calorie, low-fat diet. The primary parameter, change in body weight from baseline (time of randomization), was evaluated. in terms of body weight over time (Table 1) and percentage of subjects who lost ≥ 5% or ≥ 10% of weight (Table 2). Although weight loss was assessed for 12 months of treatment in both studies, the greatest loss occurred in the first 6 months.
The weight loss induced by orlistat 60 mg resulted in other important health benefits after 6 months of treatment, in addition to the weight loss itself. The mean relative change in total cholesterol levels was -2.4% for orlistat 60 mg (baseline 5.20 mmol / l) and +2.8% for placebo (baseline 5.26 mmol / l). ). The mean relative change in LDL cholesterol levels was -3.5% for orlistat 60 mg (baseline 3.30 mmol / l) and +3.8% for placebo (baseline 3.41 mmol / l). ). For waist circumference, the mean change was -4.5 cm for orlistat 60 mg (baseline 103.7 cm) and -3.6 cm for placebo (baseline 103.5 cm). All comparisons were statistically significant versus placebo.
05.2 Pharmacokinetic properties
Absorption
Studies in normal weight and obese volunteers have shown that absorption of orlistat is minimal. 8 hours after oral administration of 360 mg of orlistat, plasma concentrations of unchanged orlistat were not measurable (
In general, at therapeutic dosages, the finding of unchanged orlistat in plasma was occasional and in extremely low concentrations (
Distribution
The volume of distribution cannot be determined because the active substance is minimally absorbed and has no defined systemic pharmacokinetics. In vitro, orlistat is over 99% bound to plasma proteins (the major binding proteins are lipoproteins and albumin). Orlistat is insignificantly distributed in erythrocytes.
Biotransformation
Based on the results in the animal, it is likely that orlistat is metabolised predominantly within the gastrointestinal wall. In a study of obese patients, two main metabolites, M1 (hydrolyzed 4-atom lactone ring) and M3; (M1 devoid of the N-formyl leucine group), determine about 42% of the total plasma concentration, relative to the smallest fraction of the dose that is absorbed systemically.
M1 and M3; they have an open beta-lactone ring and extremely weak lipase inhibition activity (1,000 and 2,500 times lower than orlistat, respectively). In view of this reduced inhibitory capacity and reduced plasma levels at therapeutic doses (on average, 26 ng / ml and 108 ng / ml, respectively), these metabolites are considered to have no relevant pharmacological activity.
Elimination
Studies in normal weight and obese subjects have shown that excretion of the unabsorbed active substance in faeces is the major route of elimination. Approximately 97% of the administered dose was excreted in the faeces and 83% of it in the form of unchanged orlistat.
Cumulative renal excretion of all orlistat-related compounds was less than 2% of the administered dose. The time required to achieve complete excretion (faecal plus urinary) was 3-5 days. Elimination of orlistat appears similar in normal weight and obese volunteers. Orlistat, M1 and M & SUP3; are all subject to biliary excretion.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity on fertility, reproduction and development.
The medicinal use of orlistat is unlikely to pose a risk to the aquatic or terrestrial environment. However, any potential risks must be avoided (see section 6.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Capsule contents
Microcrystalline cellulose (E460)
Sodium starch glycolate
Povidone (E1201)
Sodium lauryl sulfate
Talc
Operculum
Jelly
Indigo carmine (E132)
Titanium dioxide (E171)
Sodium lauryl sulfate
Sorbitan monolaurate
Capsule printing ink
Shellac
Black iron oxide (E172)
Propylene glycol
Band
Jelly
Polysorbate 80
Indigo carmine (E132).
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years.
Discard the capsules stored for more than one month in the portable case.
06.4 Special precautions for storage
Do not store above 25 ° C.
Keep the bottle tightly closed to protect the medicine from moisture.
06.5 Nature of the immediate packaging and contents of the package
High density polyethylene (HDPE) bottle with child resistant closure containing 42, 60, 84, 90 or 120 hard capsules. The bottle also contains two sealed cylinders, which in turn contain silica gel as a desiccant.
A polystyrene / polyurethane resin case (Shuttle) that can hold 3 capsules is included in each package.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and waste from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
UB6 0NN
UK
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/07/401 / 007-011
038933053
038933014
038933026
038933038
038933040
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 23 July 2007
Date of the last renewal:
