ALLI 60 MG 120 CAPSULES (ORLISTAT)

Alli 60 Mg 120 Capsules (ORLISTAT)

ACTION AND MECHANISM

- [PANCREATIC LIPASE INHIBITOR], [INHIBITOR OF ORAL LIPID ABSORPTION]. Orlistat is a potent and specific inhibitor of gastric and pancreatic lipases, enzymes responsible for the hydrolysis of triglycerides. It acts in the light of the digestive tract, slowly joining serine residues from the active center of the enzyme, through a reversible covalent union. By inhibiting the enzyme, it prevents the formation of fatty acids and monoglycerides, and the absorption of them. Orlistat can reduce the absorption of up to 30% of the lipids contained in food, which can lead to a reduction in energy intake of 200-300 kilocalories a day. In addition to acting on lipids, orlistat also prevents the absorption of fat-soluble vitamins A, D, E and K.

PHARMACOKINETICS

Orally:
- Absorption: Oral absorption of orlistat is minimal. After oral administration of 360 mg, the plasma concentrations reached were not detectable (<5 ng / ml). In animals it has been found that the oral bioavailability of orlistat is less than 2%.
- Distribution: In in vitro studies, the small amount of orlistat absorbed circulates in plasma bound to plasma proteins (99%), especially to albumin and lipoproteins. Minimal amounts may appear in erythrocytes.
- Metabolism: It is possible that orlistat is metabolized primarily in the intestinal wall. In studies with obese patients, two main metabolites have been isolated in blood, M1, obtained by hydrolysis of the lactone ring in position 4, and M3, which is formed by eliminating an N-formyl leucine from M1. These metabolites represent 42% of the total plasma concentration. They lack pharmacological activity.
- Elimination: Orlistat is eliminated mainly by faeces (97%), with 83% unaltered. The fraction of orlistat absorbed is eliminated by renal excretion and by bile. The elimination half-life is 1-2 hours, and the time necessary to eliminate all orlistat, 3-5 days.
Pharmacokinetics in special situations:
- Renal insufficiency: No studies have been performed in patients with renal insufficiency.
- Hepatic insufficiency: No studies have been conducted in patients with hepatic insufficiency.

INDICATIONS

* EFP:
- [OVERWEIGHT]. Weight loss in adults (over 18 years of age) with overweight, with a BMI greater than or equal to 28 kg / m2, associated with low-calorie hypocaloric diet and exercise.

POSOLOGY

* MSP:
- Adults, oral: 1 tablet / 8 hours. If after 12 weeks of treatment, there is no loss of weight, it is recommended to consult the doctor and / or pharmacist, who will assess the need to suspend orlistat.
- Duration of treatment: The treatment should not be prolonged for periods longer than 6 months.
- Children and adolescents under 18 years of age, oral: The safety and efficacy of orlistat have not been evaluated.

RULES FOR THE CORRECT ADMINISTRATION

Take immediately before, during meals or at most, one hour after meals. If you do not take a meal or it has no fat, you should skip the dose of orlistat.

CONTRAINDICATIONS

- Hypersensitivity to any component of the medication.
- [MALABSORCION SYNDROME] chronic. Orlistat decreases the absorption of liposoluble lipids and vitamins, so that in these patients can cause malnutrition, and increase the phenomena of steatorrhea.
- [COLESTASIS]. Orlistat decreases postprandial concentrations of cholecystokinin by reducing the number of fatty acids present in the intestinal lumen. Although reductions in gallbladder contractility have not been proven, they can not be ruled out. Since orlistat may favor the formation of gallstones, it is not recommended to use it in patients with cholestasis.
- [ANOREXIA NERVIOSA] and [BULIMIA NERVIOSA]. Orlistat could be used abusively by patients with anorexia or bulimia nervosa. This medicine should not be used in these patients.
- Treatment with cyclosporine, oral anticoagulants (acenocoumarol, warfarin) or acarbose. Coadministration of any of these drugs with orlistat EFP is considered contraindicated. (See Interactions, Precautions).
- Pregnancy.

CONTRAINDICATIONS RELATIVE TO EXCIPIENTS

- This medicine contains starch. Patients with allergy to starch other than celiac disease should not take this medicine.

PRECAUTIONS

- [RENAL INSUFFICIENCY], [KIDNEY CALCULATIONS]. In some patients, orlistat may lead to increased urinary oxalate excretion (hyperoxaluria) and oxalate nephropathy. The doctor should be consulted before starting orlistat EFP administration.
- [DIABETES MELLITUS TYPE 2]. Weight loss in obese patients with non-insulin-dependent diabetes was lower than in obese patients without diabetes. On the other hand, when a weight loss occurs, diabetic patients can see their resistance to the action of insulin diminished, so it is necessary to monitor blood glucose more closely and consider the need to readjust the dosage (See Interactions) .
- [RECTORRAGIA]: Cases of rectal bleeding have been reported. In cases of severe and / or persistent symptoms, comprehensive clinical monitoring is advised.
- [HIPOTIROIDISM]. There have been rare cases of hypothyroidism and / or alterations of control in hypothyroid patients, possibly due to a decrease in the absorption of iodine salts and / or levothyroxine. Monitor thyroid function in patients with hypothyroidism and consider the need to adjust the dose of levothyroxine. The doctor should be consulted before initiating co-administration if orlistat EFP is used. (See Interactions).
- [NEFROPATIA], [HIPOVOLEMIA]. The use of orlistat may be associated with increased levels of oxalate in urine. Hyperoxaluria and oxalate nephropathy have been described in patients with underlying chronic nephropathy and / or hypovolaemia. Administer with caution to patients with a history of [HIPEROXALURIA] or [RENAL CALCULATIONS] by calcium oxalate.
- [ARTERIAL HYPERTENSION]. Weight loss may be accompanied by an improvement in blood pressure, so that patients on antihypertensive treatment may need to adjust the dose of drugs.
- [HIPERCOLESTEROLEMIA]. Weight loss may be accompanied by an improvement in cholesterol levels, so that in patients under lipid-lowering treatment it may be necessary to adjust the dose.
- Treatment with cyclosporine. Joint administration is not recommended; The doctor should be consulted before initiating co-administration if Orlistat EFP is used. (See Interactions, Contraindications).
- Treatment with oral anticoagulants. The coagulation parameters (INR) must be monitored. The doctor should be consulted before initiating co-administration if orlistat EFP is used. (See Interactions, Contraindications).
- Treatment with acarbose. The use of orlistat EFP is not recommended due to the absence of studies on pharmacokinetic interactions (See Interactions).
- Treatment with antiepileptics. Seizures have been reported in patients who used both treatments. The doctor should be consulted before initiating co-administration if orlistat EFP is used. (See Interactions).
- Treatment with amiodarone, or oral hormonal contraceptives. The possible interactions of orlistat with these medications could have considerable consequences, so caution is necessary. (See Interactions).
- Fat-soluble vitamins. Orlistat may interfere with the intestinal absorption of vitamins A, D, E and K. It is advisable to follow a diet rich in fruits and vegetables, and consider the need to provide vitamin supplements. If necessary, the doses of orlistat and these supplements should be separated (See Interactions).

PRECAUTIONS RELATIVE TO EXCIPIENTS

- This medicine contains starch with gluten, which should be taken into account in patients with [CELIAC DISEASE].

PATIENT TIPS

- A nutritionally balanced, moderately hypocaloric diet should be followed, with approximately 30% of the calories coming from fats. It is recommended that the diet be rich in fruits and vegetables. The daily intake of fat, carbohydrates and proteins should be distributed among the three main meals. It is advisable to continue with the diet after the end of the treatment.
- It is advisable to do regular physical exercise during and after the treatment is finished.
- The prescribed doses should not be increased.
- The consumption of alcohol should be avoided, due to the large amount of calories it provides.
- Inform the doctor or pharmacist if you are being treated with anticoagulants, cyclosporine, acarbose, levothyroxine, antiepileptic drugs, oral contraceptives or amiodarone.
- In cases of severe diarrhea, patients using oral contraceptives should use an additional contraceptive method.
- In cases of steatorrhoea, antidiarrheals that reduce intestinal transit (loperamide) should not be used.
- If fat is not swallowed in a meal, or if the patient skips a meal, the capsule corresponding to that meal will not be taken.
- The doctor or pharmacist should be informed if symptoms such as weakness, fatigue, fever, jaundice or dark urine appear. They could indicate liver damage.


- In the case of orlistat EFP it is not recommended to take 2 tablets of 27 mg instead of 1 capsule of 60 mg. The systemic absorption of the 27 mg tablets appears to be superior to that of the 60 mg capsules.

SPECIAL WARNINGS

- The advertising medication is only authorized for adults 18 years of age or older who are overweight, a BMI of 28 kg / m2 or more. If there is a medical prescription, besides being authorized for overweight (BMI 28-30 kg / m2), it can also be used in obesity (BMI> 30 kg / m2).
- The BMI is calculated by dividing the body weight (in kg) by the square of the height (in meters).
- Pay special attention to possible eating disorders.
- Diet and exercise should be part of the weight loss program, and should preferably start before starting orlistat treatment, and continue once orlistat has finished.
- Before initiating a treatment with orlistat, any organic cause of obesity should be excluded, such as untreated hypothyroidism.
- In patients under treatment with anticoagulants, it is recommended to monitor the INR before, during and after treatment with orlistat. The doctor should be consulted before initiating co-administration if orlistat EFP is used. (See Interactions).
- Cyclosporin levels should be monitored in transplant patients, and if necessary increase its dose or use Neoral forms. The doctor should be consulted before initiating co-administration if orlistat EFP is used. (See Interactions).
- In patients receiving acarbose treatment, the use of orlistat EFP is not recommended due to the absence of studies on pharmacokinetic interactions (See Interactions).
- The treatment with levothyroxine or antiepileptic should be monitored, adjusting the doses. The doctor should be consulted before initiating co-administration if orlistat EFP is used. (See Interactions).
- Other treatments that must be taken with caution are oral contraceptives and amiodarone. (See Interactions).
- The possibility of suffering gastrointestinal adverse reactions (abdominal pain, steatorrhea, flatulence) may increase if orlistat is taken with a high-fat diet (for example, 2,000 kcal / day,> 30% of calories from fats is> 67g) of fat) or with a meal rich in fats. The daily intake of fat should be distributed among the three main meals.
- In addition to monitoring body weight, it may be advisable to measure blood lipids.
- Orlistat can interfere with the intestinal absorption of the fat-soluble vitamins A, D, E and K. If it is considered necessary to provide vitamin supplements, these should be administered at least 2 hours after the dose of orlistat or at bedtime. (See Interactions).
- It is possible, although rare, that there are increases in the excretion of oxalates in urine (hyperoxaluria) and oxalate nephropathy; therefore, the doctor should be consulted before starting treatment in patients with renal insufficiency.
- While the cases of severe hepatic adverse reactions continue to be evaluated, it is advisable to inform the patient that he should consult a doctor or pharmacist about possible symptoms that could be associated with the development of liver damage (weakness, fatigue, fever, jaundice and dark urine). Other possible symptoms are: abdominal pain, nausea, vomiting, light colored stools, itching and loss of appetite.

INTERACTIONS

- Acarbosa. In the absence of studies on pharmacokinetic interactions, the concomitant administration of orlistat with acarbose should be avoided.

- Amidarona. Possible decrease in plasma levels of amiodarone, being advisable to monitor the patient. Consider the need to adjust the dose of amiodarone.

- Oral contraceptives. Although studies indicate that there is no interaction between these drugs, orlistat could indirectly reduce the availability of oral contraceptives, since there have been some cases of unforeseen pregnancies. Therefore, the use of an additional contraceptive method is recommended in cases of severe diarrhea.

- Anticoagulants (acenocoumarol, warfarin). A case has been described in which the administration of orlistat produced a decrease in INR in patients on warfarin therapy. The effects could be due to a decrease in the absorption of vitamin K. It is suggested to administer with orlistat with caution in patients undergoing anticoagulant treatment, monitoring the INR levels, and a dosage readjustment of the anticoagulant may be necessary.

- Antidiabetics (including insulins). In obese patients with type 2 diabetes, a decrease in body weight caused by orlistat may be accompanied by a decrease in resistance to insulin action. Monitor glycemia more frequently than usual and consider whether it is necessary to reduce the doses of antidiabetics.

- Antiepileptics (valproate, lamotrigine). Seizures have been reported in patients who used both treatments concomitantly. It is recommended to monitor the possibility of changes in the frequency and / or severity of seizures. The patient should consult the doctor before starting treatment with orlistat EFP.

- Antihypertensive agents (amlodipine, atenolol, enalapril, hydrochlorothiazide or losartan). There are some cases in which increases in blood pressure have been described in patients who were controlled with these drugs when co-administering orlistat. Caution is recommended in the association of these drugs.

- Cyclosporine. It is possible that orlistat produces decreases in plasma concentrations of ciclosporin, with the consequent risk of loss of its immunosuppressive effect. The effect could be due to a possible interference of the absorption of cyclosporine, as a lipophilic substance that is. In principle, concomitant use is discouraged (especially if orlistat EFP is dispensed); If this combination is unavoidable, it is recommended to monitor ciclosporin levels at the start and end of a treatment with orlistat. This interaction seems to be less important when cyclosporin is administered in the form of a microemulsion (Neoral preparations) than when administered as an oil suspension.

- Hypolipidemic agents. Weight loss may be accompanied by an improvement in cholesterol levels, so that in patients under lipid-lowering treatment it may be necessary to adjust the dose of this.

- Levothyroxine. Risk of loss of therapeutic control in hypothyroid patients due to decreased levothyroxine activity. Orlistat seems to reduce its absorption. Space the administration at least 4 hours and monitor the thyroid function, adjusting the dose of levothyroxine. The patient should consult the doctor before starting treatment with orlistat EFP.

- Fat-soluble vitamins (vitamin A, D, E and K). Orlistat may interfere with the absorption of fat-soluble vitamins. Although there are usually no decreases in the deposits of these vitamins, it may sometimes be necessary to administer a supplement. It is recommended to distance the administration of these supplements and orlistat about 2 hours or administer the supplements before going to sleep.

- Antiretroviral: Possible decrease in the oral absorption of antiretroviral. Treatment with orlistat should only be started after a careful assessment of the possible impact on the efficacy of antiretroviral treatment.

PREGNANCY

Category X of the FDA. In animal studies no toxic effects have been observed for the mother or the offspring using doses even higher than the therapeutic ones.
The use of orlistat is contraindicated during pregnancy, because weight loss offers no benefit to the mother and can be harmful to the fetus. Pregnant women are recommended a slight weight gain (never a weight loss), produced as a result of the physiological process that occurs during pregnancy. This increase must occur even in overweight and obese women.
In case of pregnancy warn the mother of the negative consequences for the fetus can have the loss of weight.

LACTATION

It is not known if orlistat is excreted in breast milk and if this could have an effect on the infant. It is recommended not to use orlistat in women who are breastfeeding.
The use of orlistat EFP is considered contraindicated in women who are breastfeeding.

CHILDREN

The safety and efficacy of orlistat in children and adolescents under 18 years of age have not been evaluated, so its use is not recommended.

ELDERLY

The safety and efficacy of orlistat in patients older than 65 years have not been evaluated, so its use is not recommended.

ADVERSE REACTIONS

Adverse reactions are mainly gastrointestinal in nature, which are frequent but transient. They are related to the inhibitory effect on the absorption of fats. Therefore, the incidence of these adverse reactions is higher in diets rich in fat, so they can be reduced by decreasing the amount of fat in the diet.
The following are described in decreasing order of severity within each frequency interval, being considered very frequent (> 10%), frequent (1-10%), infrequent (0.1-1%), or of unknown frequency (no it can be estimated from the available data, since they are data of spontaneous post-marketing notifications).
- Gastrointestinal: Very common: [ABDOMINAL PAIN], [ESTERATORREA], fecal urgency, oily spots, [DIARRHEA], [FLATULENCE] and flatulence with fecal discharge, oily evacuation, soft stools. Common: pain in the rectum, [FECAL INCONTINENCE], increased defecation, tooth and gum disorders. Unknown frequency: [DIVERTICULITIS], [RECTAL HEMORRHAGE] mild, [PANCREATITIS].
- Neurological / psychological: Very common: [CEFALEA]. Common: [ANXIETY].
- Genitourinary: Frequent: [GENITOURINARY INFECTION], [DISORDERS OF THE MENSTRUAL CYCLE]. Unknown frequency: [NEPHROPATIA] by oxalate.
- Respiratory: Very common: [INFLUENZA], upper respiratory infections. Common: [RESPIRATORY INFECTION] low.
- General: Frequent: [ASTENIA].
- Allergic / dermatological: Frequency unknown: [HYPERSENSITIVITY REACTIONS], [PRURITE], [EXANTEMATIC ERUPTIONS], [URTICARIA], [ANGIOEDEMA], [BRONCHIAL SPASM], [ANAFILAXIA], bullous eruptions.
- Hepatobiliary: Frequency unknown: [HEPATITIS] that can be serious, [COLELITIASIS], [PANCREATITIS], [INCREASE TRANSAMINASES], [INCREASE OF ALKALINE PHOSPHATASE].
- Metabolic: Very frequent: [HIPOGLUCEMIA] (occurred with a frequency> 2% and with an incidence
> or = 1% on placebo in obese patients with type 2 diabetes).
- Hematological: Frequency unknown: [HIPOPROTROMBINEMIA] and increase in INR.

OVERDOSE

Symptoms: After the administration of single doses of 800 mg or multiple doses of up to 400 mg / 8 hours, there have been no significant adverse effects. According to studies with humans and animals, any systemic effect attributable to the ability of orlistat to inhibit lipases should be rapidly reversible.
Treatment: In case of significant orlistat overdose, patient monitoring is recommended for 24 hours. The possible treatment will be symptomatic.

See leaflet Alli 60 Mg 120 Capsules

See Technical Sheet Alli 60 Mg 120 Capsules