Normofit 60 Mg 84 Capsules (Orlistat 60Mg)

Normofit (60 Mg 84Capsules) Orlistat 60Mg

NORMOFIT ACTION AND MECHANISM

- [INHIBITOR OF LIPASE PANCREATICA], [INHIBITOR OF ORAL ABSORPTION OF LIPIDS]. The Orlistat is a potent and specific inhibitor of gastric lipases and pancreatic enzymes responsible for the hydrolysis of triglycerides. It acts in the lumen of the digestive tract, slowly binding to serine residues of the enzyme's active center, through a reversible covalent bond. By inhibiting the enzyme, it prevents the formation of fatty acids and monoglycerides, and their absorption. the orlistatIt 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 per 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 achieved were not detectable (<5 ng / ml). In animals, the oral bioavailability of orlistat has been found to be less than 2%.

- Distribution: In in vitro studies, the small amount of absorbed orlistat circulates in plasma bound to plasma proteins (99%), especially to albumin and lipoproteins. Minimal amounts may appear on erythrocytes.

- Metabolism: It is possible that orlistat is metabolized mainly in the intestinal wall. In studies with obese patients, two main metabolites, M1, obtained by hydrolysis of the lactone ring in position 4, and M3, which is formed when an N-formyl leucine is removed from M1, have been isolated from the blood. These metabolites represent 42% of the total plasma concentration. They lack pharmacological activity.

- Elimination: Orlistat is eliminated mainly through faeces (97%), with 83% unchanged. The fraction of orlistat absorbed is eliminated by renal excretion and by bile. The elimination half-life is 1-2 hours, and the time required to eliminate all orlistat is 3-5 days.

Pharmacokinetics in special situations:

- Renal impairment: No studies have been performed in patients with renal impairment.

- Hepatic impairment: No studies have been performed in patients with hepatic impairment.

FOR WHOM IS NORMOFIT SUITABLE?

"PRESENTATIONS 27 and 60 mg":

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

NORMOFIT DOSAGE

"PRESENTATIONS 27 and 60 mg":

- Adults, oral: 1 tablet / 8 hours. If after 12 weeks of treatment, no weight loss is appreciated, it is recommended to consult a doctor and / or pharmacist, who will assess the need to suspend orlistat.

- Duration of treatment: Treatment should not be prolonged for periods exceeding 6 months.

- Children and adolescents under 18 years of age, oral: The safety and efficacy of orlistat have not been evaluated.

RULES FOR CORRECT ADMINISTRATION

Take immediately before, during meals or at most one hour after them. If a meal is missed or is fat-free, the orlistat dose should be skipped.

NORMOFIT CONTRAINDICATIONS

- Hypersensitivity to any component of the drug.

- [INTESTINAL MALABSORPTION] chronic. Orlistat reduces the absorption of lipids and fat-soluble vitamins, so that in these patients it can cause malnutrition, and increase the phenomena of steatorrhea.

- [CHOLESTASIS]. Orlistat decreases postprandial cholecystokinin concentrations by reducing the number of fatty acids present in the intestinal lumen. Although reductions in gallbladder contractility have not been found, they cannot be ruled out. Since orlistat may promote gallstones, it is not recommended for use in patients with cholestasis.

- [ANOREXIA NERVIOSA] and [BULIMIA]. Orlistat could be abused by patients with anorexia or bulimia nervosa. This medicine should not be used in these patients.

- Treatment with cyclosporine, with oral anticoagulants (acenocoumarol, warfarin) or with acarbose. Co-administration of any of these drugs with orlistat EFP is considered contraindicated. (See Interactions, Precautions).

- Pregnancy.

PRECAUTIONS WITH NORMOFIT

- [KIDNEY INSUFFICIENCY], [KIDNEY CALCULATIONS]. In some patients, orlistat may lead to increased excretion of oxalates in the urine (hyperoxaluria) and oxalate nephropathy. The doctor should be consulted before starting orlistat without a prescription.

- [DIABETES MELLITUS TYPE 2]. Weight loss in obese patients with non-insulin dependent diabetes was less than in obese patients without diabetes. On the other hand, when a weight loss occurs, diabetic patients may see their resistance to the action of insulin decreased, so it is necessary to monitor blood glucose more closely and consider the need to readjust the dosage (See Interactions) .

- [RECTAL HEMORRHAGE]: Cases of rectal bleeding have been reported. In cases of severe and / or persistent symptoms, close clinical monitoring is advised.

- [HYPOTHYROIDISM]. There have been rare cases of hypothyroidism and / or disturbances 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 starting co-administration if orlistat is used without a prescription. (See Interactions).

- [NEPHROPATIA], [HYPOVOLEMIA]. 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 kidney disease and / or hypovolemia. Administer with caution to patients with a history of [HYPEROXALURIA] or [KIDNEY CALCULATIONS] due to calcium oxalate.

- [ARTERIAL HYPERTENSION]. Weight loss can be accompanied by an improvement in blood pressure, so patients on antihypertensive treatment may need an adjustment in the dose of medications.

- [HYPERCHOLESTEROLEMIA]. Weight loss may be accompanied by an improvement in cholesterol levels, so that in patients on lipid-lowering treatment, a dose adjustment may be necessary.

- Treatment with cyclosporine. Joint administration is not recommended; the doctor should be consulted before starting co-administration if orlistat is used without a prescription. (See Interactions, Contraindications).

- Treatment with oral anticoagulants. Coagulation parameters (INR) should be monitored. The doctor should be consulted before starting co-administration if orlistat is used without a prescription. (See Interactions, Contraindications).

- Treatment with acarbose. The use of orlistat without a prescription is not recommended due to the absence of studies on pharmacokinetic interactions (See Interactions).

- Treatment with antiepileptic drugs. Seizures have been reported in patients using both treatments. The doctor should be consulted before starting co-administration if orlistat is used without a prescription. (See Interactions).

- Treatment with amiodarone, or oral hormonal contraceptives. The possible interactions of orlistat with these drugs could have considerable consequences, so caution is necessary. (See Interactions).

- Fat-soluble vitamins. Orlistat could 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 the need to provide vitamin supplements should be considered. If necessary, the doses of orlistat and these supplements should be separated (See Interactions).

PRECAUTIONS RELATING TO EXCIPIENTS

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

Patients with [STARCH ALLERGY] other than celiac disease should not take this medicine.

ADVICE TO THE PATIENT

- A nutritionally balanced diet should be followed, moderately hypocaloric, with approximately 30% of the calories coming from fat. 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 finishing the treatment.

- It is advisable to carry out regular physical exercise during and once the treatment is finished.

- The prescribed doses should not be increased.

- Alcohol consumption should be avoided, due to the large amount of calories it provides.

- You should inform your doctor or pharmacist if you are taking 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 steatorrhea should not be used antidiarrheals that reduce intestinal transit (loperamide).

- If no fat is ingested 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 drugs that do not need a prescription, 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 higher than that of the 60 mg capsules.

SPECIAL WARNINGS

- The drug that does not need a prescription is only authorized in overweight adults 18 years of age or older, with a BMI of 28 kg / m2 or higher. If there is a medical prescription, in addition to being authorized in overweight (BMI 28-30 kg / m2), it can also be used in obesity (BMI> 30 kg / m2).

- BMI is calculated by dividing body weight (in kg) by the square of 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 after it has ended.

- Before starting a treatment with orlistat, any organic cause of obesity, such as untreated hypothyroidism, should be excluded.

- In patients receiving anticoagulants, it is recommended to monitor the INR before, during and after treatment with orlistat. The doctor should be consulted before starting co-administration if orlistat is used without a prescription. (See Interactions).

- Cyclosporine levels should be monitored in transplant patients, and if necessary, increase its dose or use Neoral forms. The doctor should be consulted before starting co-administration if orlistat is used without a prescription. (See Interactions).

- In patients receiving acarbose, the use of orlistat without a prescription is not recommended due to the lack of studies on pharmacokinetic interactions (See Interactions).

- Treatment with levothyroxine or antiepileptics should be monitored, adjusting the doses. The doctor should be consulted before starting co-administration if orlistat is used without a prescription. (See Interactions).

- Other treatments to be careful with are oral contraceptives and amiodarone. (See Interactions).

- The possibility of 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 fat equals> 67g fat) or with a meal that is very high in fat. The daily fat intake 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 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, a doctor should be consulted before starting treatment in patients with renal failure.

- While the cases of serious hepatic adverse reactions are still being evaluated, it is advisable to inform the patient that they should consult the doctor or pharmacist of 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.

NORMOFIT INTERACTIONS

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

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

- 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 specific cases of unexpected pregnancies. Therefore, the use of an additional contraceptive method is recommended in cases of severe diarrhea.

- Anticoagulants (acenocoumarol, warfarin). Some cases have been described in which the administration of orlistat caused a decrease in INR in patients receiving warfarin. The effects could be due to a decrease in the absorption of vitamin K. It is suggested to administer orlistat with caution in patients undergoing anticoagulant treatment, monitoring INR levels, and a dosage adjustment of the anticoagulant may be necessary.

- Antidiabetic drugs (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 the action of insulin. Monitor blood glucose more frequently than usual and consider whether it is necessary to reduce the doses of antidiabetic drugs.

- Antiepileptics (valproate, lamotrigine). Seizures have been reported in patients using both treatments concomitantly. Monitoring is recommended for the possibility of changes in seizure frequency and / or severity. The patient should consult a doctor before starting treatment with orlistat EFP.

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

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

- Lipid-lowering drugs. Weight loss may be accompanied by an improvement in cholesterol levels, so that in patients on lipid-lowering treatment, it may be necessary to adjust its dose.

- Levothyroxine. Risk of loss of therapeutic control in hypothyroid patients due to decreased levothyroxine activity. Orlistat appears to reduce its absorption. Space the administration at least 4 hours and monitor thyroid function, adjusting the dose of levothyroxine. The patient should consult a 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 decreases in the stores of these vitamins are not usually observed, sometimes a supplement may be necessary. It is recommended to distance the administration of these supplements and orlistat about 2 hours or to administer the supplements before going to sleep.

- Antiretroviral: Possible decrease in oral absorption of antiretroviral. Orlistat treatment should only be initiated after careful assessment of the possible impact on the efficacy of antiretroviral therapy.

PREGNANCY

Safety in animals : in animal studies no toxic effects for the mother or the offspring have been observed using doses even higher than therapeutic ones.

Safety in humans : the use of orlistat is contraindicated during pregnancy, because weight loss offers no benefits for the mother and may be harmful to the fetus. Pregnant women are recommended a slight weight gain (never weight loss), produced as a consequence of the physiological process that occurs during pregnancy. This increase should occur even in overweight and obese women. In case of pregnancy, warn the mother of the negative consequences that weight loss may have for the fetus.

Effects on Fertility : Animal studies do not suggest harmful effects on fertility.

LACTATION

It is not known whether orlistat is excreted in human milk and if this could have an effect on the nursing infant. It is recommended not to use orlistat in lactating women.

The use of orlistat EFP is considered contraindicated in lactating women.

CHILDREN

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

SENIORS

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

ADVERSE REACTIONS OF NORMOFIT

Adverse reactions are primarily gastrointestinal in nature, which are usually 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 the case of high-fat diets, so they can be reduced by reducing the amount of fat in the diet.

Adverse reactions are described according to each frequency range, being considered very common (> 10%), common (1-10%), uncommon (0.1-1%), rare (0.01-0.1%) , very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data).

- Gastrointestinal: Very common: [ABDOMINAL PAIN], [STEATORRHEA], fecal urgency, oily spots, [DIARRHEA], [FLATULENCE] and flatulence with fecal discharge, oily stool, loose stools. Common: rectal pain, [FECAL INCONTINENCE], increased defecation, tooth and gum disorders. Unknown frequency: [INTESTINAL DIVERTICULITIS], [RECTAL HEMORRHAGE] mild, [PANCREATITIS].

- Neurological / psychological: Very common: [HEADACHE]. Common: [ANXIETY].

- Genitourinary: Common: [GENITOURINARY INFECTION], [DISORDERS OF THE MENSTRUAL CYCLE]. Unknown frequency: [NEFROPATIA] due to oxalate.

- Respiratory: Very common: [FLU], upper respiratory infections. Common: [RESPIRATORY INFECTION] low.

- General: Frequent: [ASTENIA].

- Allergic / dermatological: Unknown frequency: [HYPERSENSITIVITY REACTIONS], [PRURITO], [EXANTEMATIC ERUPTIONS], [URTICARIA], [ANGIOEDEMA], [BRONCHIAL SPASM], [ANAPHYLAXIA], bullous eruptions.

- Hepatobiliary: Unknown frequency: [HEPATITIS] which can be serious, [CHOLELITHIASIS], [PANCREATITIS], [INCREASE IN TRANSAMINASES], [INCREASE IN ALKALINE PHOSPHATASE].

- Metabolic: Very common: [HYPOGLYCAEMIA] (occurred with a frequency> 2% and with an

> or = 1% over placebo in obese patients with type 2 diabetes).

- Hematologic: Unknown frequency: [HYPOPROTHROMBINEMIA] and increased INR.

OVERDOSE

Symptoms: After the administration of single doses of 800 mg or multiple doses of up to 400 mg / 8 hours, no significant adverse effects have been evidenced. Based on human and animal studies, any systemic effects attributable to orlistat's ability to inhibit lipases should be rapidly reversible.

Treatment: In the event of a major orlistat overdose, 24-hour patient monitoring is recommended. Possible treatment will be symptomatic.

Normofit 60 Mg 84 Capsules Leaflet