Composition, structure and packing
Hard gelatin capsules, with a yellow body and blue cap, surcharged "10", the contents of capsules - white or almost white, easy-flowing powder. 1 capsule. sibutramine hydrochloride monohydrate 10 mg. Excipients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, indigodin (E132), titanium dioxide (E171), sodium lauryl sulfate, black (gray), quinoline yellow.
Hard gelatin capsules with a white body and blue cap, surcharged "15", the contents of capsules - white or almost white, easy-flowing powder. 1 capsule. sibutramine hydrochloride monohydrate 15 mg. Excipients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, indigotine (E132), titanium dioxide (E171), gelatin, sodium lauryl sulfate, black (gray), quinoline yellow.
Clinico-pharmacological group: Drug for treatment of obesity central action.
Pharmacological action
Drug to treat obesity. Sibutramine is a prodrug and exerts its effect in vivo by metabolites (primary and secondary amines), which inhibit reuptake of monoamines (especially serotonin and norepinephrine). Increased content of neurotransmitters in synapses increases the activity of central 5-HT-serotonin and adrenergic receptors, thus increasing feelings of satiety and reduce the need for food, as well as an increase termoproduktsii. Indirectly activating the β3-adrenergic receptors, sibutramine acts on the brown adipose tissue. Sibutramine and its metabolites have no effect on the release of monoamines, not inhibit MAO, have no affinity to the large number of neurotransmitter receptors, including serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C), adrenergic (β1 , β2, β3, α1, α2), dopamine (D1, D2), muscarinic, histamine (H1), benzodiazepine and NMDA-receptors.
Pharmacokinetics
Absorption, distribution, metabolism
After taking the drug inside sibutramine is rapidly absorbed from the gastrointestinal tract. Time to reach Cmax was 1.2 hours sibutramine Sibutramine almost completely metabolized in the liver with the involvement of CYP 3A4 isoenzyme with the formation of mono-(dismetilsibutramin) and di-dismetil (di-dismetilsibutramin) forms active metabolites (M1 and M2), and by hydroxylation and conjugation with the formation of inactive metabolites. After a single dose of the drug orally at a dose of 15 mg Cmax of M1 and M2 is 4 ng / ml (3.2-4.8 ng / ml) and 6.4 ng / ml (5.6-7.2 ng / ml), respectively. Reception with food increases the time to reach and reduces the value of Cmax dismetil metabolites at 3 h and 30% respectively, no influence on the AUC dismetil metabolites. Fast and well distributed in tissues.
Protein binding sibutramine - 97%, M1 and M2 - 94%.
Withdrawal
T1 / 2 sibutramine - 1.1 h, M1 - 14 h, M2 - 16 hours is derived mainly kidneys as inactive metabolites.
Pharmacokinetics in special clinical situations
In renal insufficiency, the main pharmacokinetic parameters (Cmax, T1 / 2 and AUC) did not significantly change.
Statement
alimentary obesity with a body mass index (BMI) 30 kg/m2 or more;
alimentary obesity with a BMI of 27 kg/m2 or more in combination with diabetes mellitus type 2 (insulin-dependent) or dyslipoproteinemia.
Dosage regimen
Dose was set individually, depending on tolerability and clinical effectiveness. The initial dose is 10 mg. In case of insufficient efficacy (weight loss less than 2 kg in 4 weeks), but only if well tolerated daily dose may be increased to 15 mg. If, after increasing dose efficacy remains insufficient (weight loss less than 2 kg for 4 weeks), the treatments are not appropriate. Capsules Meridia should be taken in the morning, without chewing, and drinking plenty of fluids (water glass).
The drug can be taken on an empty stomach and combine with the meal. We should not continue treatment for more than 3 months to patients who during this time (3 months) failed to achieve weight loss by 5% from baseline. Treatment should not continue if the therapy Meridia after weight-loss achieved patients gain body weight of 3 kg or more. The duration of treatment Meridia should not exceed 2 years as against a longer period of drug administration data on the effectiveness and safety of missing.
Side effect
The most common side effects occur at the beginning of treatment (in the first 4 weeks). Their severity and frequency over time, weaken. Side effects are usually slight and reversible. Side effects, depending on the impact on the organs and systems, presented in the following order: often -> 10%, sometimes - 1-10%, rare - <1%.
From the central nervous system and peripheral nervous system: often - insomnia, sometimes - headache, dizziness, anxiety, paresthesias, changes in taste.
Since the cardiovascular system: sometimes - tachycardia (increased heart rate by 3-7 bpm), a feeling the heartbeat, increased blood pressure (at rest by 1-3 mm Hg), vasodilatation.
In some cases, does not exclude a more pronounced increase in blood pressure and heart rate. Clinically significant changes in the level of blood pressure and heart rate are recorded mainly in the beginning of treatment (in the first 4-8 weeks).
On the part of the digestive system: often - dry mouth, loss of appetite, constipation, and sometimes - nausea, aggravation of hemorrhoids. Other: sometimes - increased sweating. In individual cases, describes the following clinically significant side effects: dysmenorrhea, edema, influenza-like syndrome, skin itching, backache, abdominal pain, a paradoxical increase in appetite, thirst, rhinitis, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, acute interstitial nephritis, bleeding, purpura Henoch's, seizures, thrombocytopenia, transient increase in liver enzymes in blood plasma.
One patient with schizoaffective disorder which supposedly existed before treatment, after treatment, developed acute psychosis.
Contraindications
presence of organic causes of obesity (eg, hypothyroidism);
serious eating disorders (anorexia nervosa or bulimia nervosa);
mental illness;
Syndrome Gilles de la Tourette (chronic generalized tick);
simultaneous reception of MAO inhibitors (eg, phentermine, fenfluramina, deksfenfluramina, etilamfetamina, ephedrine), or using them for 2 weeks prior to the appointment Meridia; serotonin reuptake inhibitors, sleeping pills, medicines that contain tryptophan, other drugs of central action to reduce body weight;
CHD, chronic heart failure in the stage of decompensation, congenital heart disease, occlusive peripheral arterial disease, tachycardia, arrhythmia, cerebrovascular disease (stroke, transient ischemic attacks);
uncontrolled hypertension (blood pressure above 145/90 mm Hg);
thyrotoxicosis;
severe disorders of liver function and / or kidneys;
benign prostate hyperplasia;
pheochromocytoma;
angle-closure glaucoma;
established drug, drug or alcohol addiction;
Pregnancy
Lactation (breastfeeding);
childhood and adolescence to 18 years;
age 65;
Hypersensitivity to sibutramine or to other components of the drug.
Precautions should be prescribed the drug for arrhythmia in history, chronic heart failure, coronary artery disease (including a history), cholelithiasis, hypertension (controlled and a history), neurological disorders (including delayed mental development, and seizures (in m . hours in history), abnormal liver function and / or kidney mild to moderate severity, motor and verbal ticks in history.
Pregnancy and lactation
Do not take the drug Meridia during pregnancy and lactation (breastfeeding), because so far there is not enough research on the safety of Meridia impact on the fetus. Women of childbearing age who take the drug Meridia should use methods of contraception.
Application for violations of liver function
With caution is prescribed for violations of the liver function mild to moderate severity. In severe liver problems drug contraindications
Application for violations of renal function
With caution is prescribed for violations of renal function with mild and moderate severity. In severe renal dysfunction drug is contraindicated in
Cautions
The drug Meridia should be used only in cases where non-drug interventions to reduce body weight (diet and physical activity) are ineffective (loss of body weight within 3 months was less than 5 kg). Treatment Meridia should be carried out within the framework of comprehensive therapy for weight loss under medical supervision, which has practical experience in the treatment of obesity. Comprehensive therapy includes a change in dietary habits and lifestyles, and increasing physical activity.
Patients need to change your lifestyle and habits so that after completion of treatment to ensure that the achieved reduction of body weight. Patients should be made clear that failure to comply with these requirements would lead to repeated weight gain and the need for retreatment. During the administration of the drug Meridia is necessary to control the level of blood pressure and heart rate: in the first 2 months - every 2 weeks and then monthly.
In patients with hypertension control should be implemented very carefully and at shorter intervals. If a control measure blood pressure twice higher than the level of 145/90 mm Hg, reception Meridia should be suspended.
Precautions should be prescribed Meridia in conjunction with drugs, extending the interval QT, including blockers of histamine H1-receptor (astemizol, terfenadin), antiarrhythmics (amiodarone, quinidine, flekainid, meksiletin, propafenone, sotalol), tsizapridom, pimozidom, sertindolom and tricyclic antidepressants. This applies to states, which may result in lengthening the interval QT (eg, gipomagniemiya). The interval between administration of MAO inhibitors (including furazolidone, procarbazine, selegiline) and Meridia should not be less than 2 weeks. Although not a relation between the intake of sibutramine and the development of primary pulmonary hypertension, but the application of the drug Meridia is necessary to pay attention to the emergence of progressive respiratory failure, chest pain and swelling in the legs.
When there are missing doses of Meridia should not be taken in the following method double dose of the drug, further encouraged to continue taking the drug scheme. Reactions to the abolition of the drug (headache, increased appetite) are rare. There is no evidence that after the withdrawal of the drug observed withdrawal syndrome, withdrawal, or mood disorder.
During the drug should not take alcoholic drinks, because intake of alcohol is absolutely not compatible with the recommended while taking Meridia dietary interventions.
Effects on ability to drive motor vehicles, and ypravleniyu mechanisms
Drugs affecting the CNS, may limit mental activity, memory and reaction speed. Although studies sibutramine did not affect these functions, yet taking the drug Meridia may limit the ability to drive motor vehicles and management mechanisms.
Overdose
There are very limited data about the overdose sibutramine. Specific signs of overdose are not known, however, should consider the possibility of a more pronounced manifestation of side effects. The patient must notify the attending physician in case of alleged overdose. Treatment: There is no specific antidote; should ensure free breathing, observe the state of the cardiovascular system, the need for a symptomatic therapy. Following the appointment of activated charcoal, gastric lavage, with an increase in blood pressure and tachycardia - beta-blockers. The effectiveness of forced diuresis or hemodialysis is not installed.
Drug Interactions
Simultaneous reception from Meridia isoenzyme CYP3A4 inhibitors (ketoconazole, erythromycin, troleandomitsin, cyclosporine) increases the concentration of metabolites of sibutramine with an increase in heart rate and clinically insignificant prolongation of the interval QT. Rifampicin, a macrolide antibiotics, phenytoin, carbamazepine, phenobarbital and dexamethasone may accelerate the metabolism of sibutramine.
With simultaneous use of Meridia with selective serotonin reuptake inhibitors (antidepressants), with preparations for the treatment of migraine (sumatriptan, dihydroergotamine), a potent analgesics (pentazocine, pethidine, fentanyl), with antitussive drugs (dextromethorphan) in rare cases may develop serotonin syndrome.
Drug Meridia Drug Interactions with drugs that increase blood pressure and heart rate, with antitussives, anti-allergic drugs are currently not fully understood. Meridia does not affect the validity of oral contraceptives. At the same time receiving sibutramine and ethanol, there has been a tightening of the latter.
Terms and Conditions of storage
List B. The drug should be kept dry and away from children at or above 25 ° C. Shelf life - 3 years.
Hard gelatin capsules, with a yellow body and blue cap, surcharged "10", the contents of capsules - white or almost white, easy-flowing powder. 1 capsule. sibutramine hydrochloride monohydrate 10 mg. Excipients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, indigodin (E132), titanium dioxide (E171), sodium lauryl sulfate, black (gray), quinoline yellow.
Hard gelatin capsules with a white body and blue cap, surcharged "15", the contents of capsules - white or almost white, easy-flowing powder. 1 capsule. sibutramine hydrochloride monohydrate 15 mg. Excipients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, indigotine (E132), titanium dioxide (E171), gelatin, sodium lauryl sulfate, black (gray), quinoline yellow.
Clinico-pharmacological group: Drug for treatment of obesity central action.
Pharmacological action
Drug to treat obesity. Sibutramine is a prodrug and exerts its effect in vivo by metabolites (primary and secondary amines), which inhibit reuptake of monoamines (especially serotonin and norepinephrine). Increased content of neurotransmitters in synapses increases the activity of central 5-HT-serotonin and adrenergic receptors, thus increasing feelings of satiety and reduce the need for food, as well as an increase termoproduktsii. Indirectly activating the β3-adrenergic receptors, sibutramine acts on the brown adipose tissue. Sibutramine and its metabolites have no effect on the release of monoamines, not inhibit MAO, have no affinity to the large number of neurotransmitter receptors, including serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C), adrenergic (β1 , β2, β3, α1, α2), dopamine (D1, D2), muscarinic, histamine (H1), benzodiazepine and NMDA-receptors.
Pharmacokinetics
Absorption, distribution, metabolism
After taking the drug inside sibutramine is rapidly absorbed from the gastrointestinal tract. Time to reach Cmax was 1.2 hours sibutramine Sibutramine almost completely metabolized in the liver with the involvement of CYP 3A4 isoenzyme with the formation of mono-(dismetilsibutramin) and di-dismetil (di-dismetilsibutramin) forms active metabolites (M1 and M2), and by hydroxylation and conjugation with the formation of inactive metabolites. After a single dose of the drug orally at a dose of 15 mg Cmax of M1 and M2 is 4 ng / ml (3.2-4.8 ng / ml) and 6.4 ng / ml (5.6-7.2 ng / ml), respectively. Reception with food increases the time to reach and reduces the value of Cmax dismetil metabolites at 3 h and 30% respectively, no influence on the AUC dismetil metabolites. Fast and well distributed in tissues.
Protein binding sibutramine - 97%, M1 and M2 - 94%.
Withdrawal
T1 / 2 sibutramine - 1.1 h, M1 - 14 h, M2 - 16 hours is derived mainly kidneys as inactive metabolites.
Pharmacokinetics in special clinical situations
In renal insufficiency, the main pharmacokinetic parameters (Cmax, T1 / 2 and AUC) did not significantly change.
Statement
alimentary obesity with a body mass index (BMI) 30 kg/m2 or more;
alimentary obesity with a BMI of 27 kg/m2 or more in combination with diabetes mellitus type 2 (insulin-dependent) or dyslipoproteinemia.
Dosage regimen
Dose was set individually, depending on tolerability and clinical effectiveness. The initial dose is 10 mg. In case of insufficient efficacy (weight loss less than 2 kg in 4 weeks), but only if well tolerated daily dose may be increased to 15 mg. If, after increasing dose efficacy remains insufficient (weight loss less than 2 kg for 4 weeks), the treatments are not appropriate. Capsules Meridia should be taken in the morning, without chewing, and drinking plenty of fluids (water glass).
The drug can be taken on an empty stomach and combine with the meal. We should not continue treatment for more than 3 months to patients who during this time (3 months) failed to achieve weight loss by 5% from baseline. Treatment should not continue if the therapy Meridia after weight-loss achieved patients gain body weight of 3 kg or more. The duration of treatment Meridia should not exceed 2 years as against a longer period of drug administration data on the effectiveness and safety of missing.
Side effect
The most common side effects occur at the beginning of treatment (in the first 4 weeks). Their severity and frequency over time, weaken. Side effects are usually slight and reversible. Side effects, depending on the impact on the organs and systems, presented in the following order: often -> 10%, sometimes - 1-10%, rare - <1%.
From the central nervous system and peripheral nervous system: often - insomnia, sometimes - headache, dizziness, anxiety, paresthesias, changes in taste.
Since the cardiovascular system: sometimes - tachycardia (increased heart rate by 3-7 bpm), a feeling the heartbeat, increased blood pressure (at rest by 1-3 mm Hg), vasodilatation.
In some cases, does not exclude a more pronounced increase in blood pressure and heart rate. Clinically significant changes in the level of blood pressure and heart rate are recorded mainly in the beginning of treatment (in the first 4-8 weeks).
On the part of the digestive system: often - dry mouth, loss of appetite, constipation, and sometimes - nausea, aggravation of hemorrhoids. Other: sometimes - increased sweating. In individual cases, describes the following clinically significant side effects: dysmenorrhea, edema, influenza-like syndrome, skin itching, backache, abdominal pain, a paradoxical increase in appetite, thirst, rhinitis, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, acute interstitial nephritis, bleeding, purpura Henoch's, seizures, thrombocytopenia, transient increase in liver enzymes in blood plasma.
One patient with schizoaffective disorder which supposedly existed before treatment, after treatment, developed acute psychosis.
Contraindications
presence of organic causes of obesity (eg, hypothyroidism);
serious eating disorders (anorexia nervosa or bulimia nervosa);
mental illness;
Syndrome Gilles de la Tourette (chronic generalized tick);
simultaneous reception of MAO inhibitors (eg, phentermine, fenfluramina, deksfenfluramina, etilamfetamina, ephedrine), or using them for 2 weeks prior to the appointment Meridia; serotonin reuptake inhibitors, sleeping pills, medicines that contain tryptophan, other drugs of central action to reduce body weight;
CHD, chronic heart failure in the stage of decompensation, congenital heart disease, occlusive peripheral arterial disease, tachycardia, arrhythmia, cerebrovascular disease (stroke, transient ischemic attacks);
uncontrolled hypertension (blood pressure above 145/90 mm Hg);
thyrotoxicosis;
severe disorders of liver function and / or kidneys;
benign prostate hyperplasia;
pheochromocytoma;
angle-closure glaucoma;
established drug, drug or alcohol addiction;
Pregnancy
Lactation (breastfeeding);
childhood and adolescence to 18 years;
age 65;
Hypersensitivity to sibutramine or to other components of the drug.
Precautions should be prescribed the drug for arrhythmia in history, chronic heart failure, coronary artery disease (including a history), cholelithiasis, hypertension (controlled and a history), neurological disorders (including delayed mental development, and seizures (in m . hours in history), abnormal liver function and / or kidney mild to moderate severity, motor and verbal ticks in history.
Pregnancy and lactation
Do not take the drug Meridia during pregnancy and lactation (breastfeeding), because so far there is not enough research on the safety of Meridia impact on the fetus. Women of childbearing age who take the drug Meridia should use methods of contraception.
Application for violations of liver function
With caution is prescribed for violations of the liver function mild to moderate severity. In severe liver problems drug contraindications
Application for violations of renal function
With caution is prescribed for violations of renal function with mild and moderate severity. In severe renal dysfunction drug is contraindicated in
Cautions
The drug Meridia should be used only in cases where non-drug interventions to reduce body weight (diet and physical activity) are ineffective (loss of body weight within 3 months was less than 5 kg). Treatment Meridia should be carried out within the framework of comprehensive therapy for weight loss under medical supervision, which has practical experience in the treatment of obesity. Comprehensive therapy includes a change in dietary habits and lifestyles, and increasing physical activity.
Patients need to change your lifestyle and habits so that after completion of treatment to ensure that the achieved reduction of body weight. Patients should be made clear that failure to comply with these requirements would lead to repeated weight gain and the need for retreatment. During the administration of the drug Meridia is necessary to control the level of blood pressure and heart rate: in the first 2 months - every 2 weeks and then monthly.
In patients with hypertension control should be implemented very carefully and at shorter intervals. If a control measure blood pressure twice higher than the level of 145/90 mm Hg, reception Meridia should be suspended.
Precautions should be prescribed Meridia in conjunction with drugs, extending the interval QT, including blockers of histamine H1-receptor (astemizol, terfenadin), antiarrhythmics (amiodarone, quinidine, flekainid, meksiletin, propafenone, sotalol), tsizapridom, pimozidom, sertindolom and tricyclic antidepressants. This applies to states, which may result in lengthening the interval QT (eg, gipomagniemiya). The interval between administration of MAO inhibitors (including furazolidone, procarbazine, selegiline) and Meridia should not be less than 2 weeks. Although not a relation between the intake of sibutramine and the development of primary pulmonary hypertension, but the application of the drug Meridia is necessary to pay attention to the emergence of progressive respiratory failure, chest pain and swelling in the legs.
When there are missing doses of Meridia should not be taken in the following method double dose of the drug, further encouraged to continue taking the drug scheme. Reactions to the abolition of the drug (headache, increased appetite) are rare. There is no evidence that after the withdrawal of the drug observed withdrawal syndrome, withdrawal, or mood disorder.
During the drug should not take alcoholic drinks, because intake of alcohol is absolutely not compatible with the recommended while taking Meridia dietary interventions.
Effects on ability to drive motor vehicles, and ypravleniyu mechanisms
Drugs affecting the CNS, may limit mental activity, memory and reaction speed. Although studies sibutramine did not affect these functions, yet taking the drug Meridia may limit the ability to drive motor vehicles and management mechanisms.
Overdose
There are very limited data about the overdose sibutramine. Specific signs of overdose are not known, however, should consider the possibility of a more pronounced manifestation of side effects. The patient must notify the attending physician in case of alleged overdose. Treatment: There is no specific antidote; should ensure free breathing, observe the state of the cardiovascular system, the need for a symptomatic therapy. Following the appointment of activated charcoal, gastric lavage, with an increase in blood pressure and tachycardia - beta-blockers. The effectiveness of forced diuresis or hemodialysis is not installed.
Drug Interactions
Simultaneous reception from Meridia isoenzyme CYP3A4 inhibitors (ketoconazole, erythromycin, troleandomitsin, cyclosporine) increases the concentration of metabolites of sibutramine with an increase in heart rate and clinically insignificant prolongation of the interval QT. Rifampicin, a macrolide antibiotics, phenytoin, carbamazepine, phenobarbital and dexamethasone may accelerate the metabolism of sibutramine.
With simultaneous use of Meridia with selective serotonin reuptake inhibitors (antidepressants), with preparations for the treatment of migraine (sumatriptan, dihydroergotamine), a potent analgesics (pentazocine, pethidine, fentanyl), with antitussive drugs (dextromethorphan) in rare cases may develop serotonin syndrome.
Drug Meridia Drug Interactions with drugs that increase blood pressure and heart rate, with antitussives, anti-allergic drugs are currently not fully understood. Meridia does not affect the validity of oral contraceptives. At the same time receiving sibutramine and ethanol, there has been a tightening of the latter.
Terms and Conditions of storage
List B. The drug should be kept dry and away from children at or above 25 ° C. Shelf life - 3 years.
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