Composition, form of production and packaging
Capsules number 2 in blue; the contents of the capsules are white or white powder with a slightly yellowish tint of color.
1 caps.
sibutramine hydrochloride monohydrate 10 mg
cellulose microcrystalline 158.5 mg
[PRING] calcium stearate.
The composition of the shell of the capsule: dye titanium dioxide, dye azorubin, dye patented blue, gelatin.
10 pieces. - Cellular outline packaging (aluminum / PVC) (3) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (6) - cardboard packs.
Capsules number 2 in blue; the contents of the capsules are white or white powder with a slightly yellowish tint of color.
1 caps.
sibutramine hydrochloride monohydrate 15 mg
cellulose microcrystalline 153.5 mg
[PRING] calcium stearate.
The composition of the capsule shell: titanium dioxide dye, the dye patented blue, gelatin.
10 pieces. - Cellular outline packaging (aluminum / PVC) (3) - cardboard packs.
10 pieces. - Cellular outline packaging (aluminum / PVC) (6) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
PHARMACHOLOGIC EFFECT
Combination drug for the treatment of obesity, the effect of which is due to its constituent components. Sibutramine is a prodrug and shows its effect in vivo due to metabolites (primary and secondary amines) inhibiting the reuptake of monoamines (mainly serotonin and norepinephrine). An increase in the content of neurotransmitters in the synapses increases the activity of central serotonin 5-HT receptors and adrenoreceptors, which increases the feeling of satiety and reduced food requirements, as well as an increase in thermal production. Indirectly activating? 3- adrenoreceptors, sibutramine affects the brown adipose tissue. The decrease in body weight is accompanied by an increase in the concentration in the blood serum of HDL and the decrease in the amount of triglycerides, total cholesterol, LDL, uric acid.
Sibutramine and its metabolites do not affect the release of monoamines, do not inhibit MAO; have no affinity for a large number of neurotransmitter receptors, including serotonin (5-HT 1 , 5-HT 1A , 5-HT 1B , 5-HT 2A , 5-HT 2C ), adrenoreceptors (? 1 ,? 2 ,? 3 ,? 1 ,? 2 ), dopamine (D 1 , D 2 ), muscarinic, histamine (H 1 ), benzodiazepine and NMDA receptors.
Microcrystalline cellulose is an enterosorbent, it possesses sorption properties and nonspecific detoxification action. Binds and removes from the body various microorganisms, the products of their vital functions, toxins of exogenous and endogenous nature, allergens, xenobiotics, as well as an excess of certain metabolic products and metabolites responsible for the development of endogenous toxicosis.
PHARMACOKINETICS
Absorption, distribution, metabolism
After taking the drug inside, sibutramine is rapidly absorbed from the digestive tract, no less than 77%. It is subjected to the effect of the "first passage" through the liver and biotransformed with the participation of the cytochrome P450 3A4 isoenzyme with the formation of two active metabolites (mono- and didesmethylsibutramine). After taking a single dose of 15 mg C max monodesmethylsibutramine is 4 ng / ml (3.2-4.8 ng / ml), didlesmethylsibutramine - 6.4 ng / ml (5.6-7.2 ng / ml). C max sibutramine is achieved after 1.2 hours, active metabolites - after 3-4 hours. Reception simultaneously with food reduces C max metabolites by 30% and increases the time it reaches by 3 h without changing the AUC. Quickly distributed into tissues. The binding of sibutramine to plasma proteins is 97%, and mono- and didesmethylsibutramine 94%. C ss of active metabolites in the blood is reached within 4 days after the start of treatment and approximately 2 times higher than the plasma level after taking a single dose.
Excretion
T 1/2 sibutramine 1.1 h, monodesmethylsibutramine 14 h, didles methyl sibutramine 16 h. Active metabolites undergo hydroxylation and conjugation to form inactive metabolites, which are excreted mainly by the kidneys.
INDICATIONS
To reduce body weight with the following conditions:
- alimentary obesity with a body mass index (BMI) of 30 kg / m 2 and more;
- nutritional obesity with a BMI of 27 kg / m 2 or more in combination with other risk factors due to overweight (type 2 diabetes / non-insulin-independent / or dyslipoproteinemia).
DOSING MODE
Reduxin В® is prescribed by mouth 1 time / day. The dose is set individually, depending on the tolerability and clinical effectiveness. The recommended initial dose is 10 mg, with poor tolerability, a dose of 5 mg is possible. Capsules should be taken in the morning without chewing and drinking with a sufficient amount of liquid. The drug can be taken either on an empty stomach or combined with a meal.
If within 4 weeks from the beginning of treatment there is no reduction in body weight by 5% or more, then the dose is increased to 15 mg / day. The duration of therapy with Reduxin should not exceed 3 months in patients who do not respond well enough to therapy (ie, they can not reduce the weight by 5% of the initial body weight during the 3 months of treatment). Treatment should not be continued if, in further therapy (after the achieved weight loss), the patient again adds 3 kg or more in the body mass.
The total duration of therapy should not exceed 2 years, since there is no data on efficacy and safety for a longer period of sibutramine intake.
Therapy Reduxin should be conducted by a doctor who has a practical experience in the treatment of obesity. The intake of the drug should be combined with diet and exercise.
SIDE EFFECT
Side effects, depending on the effect on organs and organ systems, are presented in the following order (often -> 10%, sometimes - 1-10%, rarely - <1%).
From the side of the central nervous system and peripheral nervous system: often - dry mouth, insomnia; sometimes - headache, dizziness, anxiety, paresthesia, as well as changes in taste; in isolated cases - back pain, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, convulsions.
In one patient with schizoaffective disorder, which presumably existed before treatment, acute psychosis developed after treatment.
From the cardiovascular system: sometimes - tachycardia, palpitations, increased blood pressure, vasodilation. There is a moderate rise in blood pressure at rest by 1-3 mm Hg. and a moderate increase in heart rate at 3-7 beats per minute. In some cases, more pronounced increases in blood pressure and heart rate are not excluded.Clinically significant changes in blood pressure and pulse level are registered mainly at the beginning of treatment (in the first 4-8 weeks).
From the digestive system: often - loss of appetite, constipation; sometimes - nausea, exacerbation of hemorrhoids. With a tendency to constipation in the first days, control over the evacuation function of the intestine is necessary. If there is constipation, stop taking and take a laxative. In isolated cases, pain in the abdomen, a paradoxical increase in appetite, a transient increase in the activity of liver enzymes.
Dermatological reactions: sometimes - sweating; in isolated cases - skin itch, purple Shenlaine-Genocha (hemorrhages in the skin).
From the whole organism: in single cases the following undesirable clinically significant phenomena are described: dysmenorrhea, edema, flu-like syndrome, thirst, rhinitis, acute interstitial nephritis, bleeding, thrombocytopenia.
Reactions to cancellation, such as headache or increased appetite, are rare. There is no evidence that after treatment abstinence syndrome, withdrawal or mood disorder occurs.
Most often, side effects occur at the beginning of treatment (in the first 4 weeks). Their severity and frequency diminish over time. Side effects are generally light and reversible.
CONTRAINDICATIONS
- the presence of organic causes of obesity (eg, hypothyroidism);
- Serious eating disorders (anorexia nervosa or bulimia nervosa);
- mental illness;
- Gilles de la Tourette's syndrome (generalized tics);
- simultaneous administration of MAO inhibitors (eg, phentermine, fenfluramine, dexfenfluramine, ethylamphetamine, ephedrine) or their use for 2 weeks before the administration of ReduxinВ®; the use of other drugs acting on the central nervous system (eg, antidepressants, neuroleptics); drugs prescribed for sleep disorders containing tryptophan, as well as other drugs of central action to reduce body weight;
- IHD, decompensated chronic heart failure, congenital heart defects, occlusive diseases of peripheral arteries, tachycardia, arrhythmias, cerebrovascular diseases (stroke, transient disorders of cerebral circulation);
- uncontrolled arterial hypertension (blood pressure above 145/90 mm Hg);
- thyrotoxicosis;
severe hepatic impairment;
- severe renal dysfunction;
benign prostatic hyperplasia;
- pheochromocytoma;
- an angle-closure glaucoma;
- established drug, drug or alcohol dependence;
- Pregnancy;
- lactation (breastfeeding);
- children and adolescence under 18;
- The elderly are older than 65;
- established hypersensitivity to sibutramine or to other components of the drug.
Caution should be given to the drug in the following conditions: history of arrhythmia, chronic circulatory failure, coronary artery disease (including history), cholelithiasis, hypertension (controlled and in history), neurological disorders, including mental retardation and convulsions (including in anamnesis), violations of the liver and / or kidneys of mild and moderate severity, motor and verbal tics in the anamnesis.
PREGNANCY AND LACTATION
The drug should not be used during pregnancy because of the lack of a sufficiently convincing number of studies of the safety of the effects of sibutramine on the fetus.
Women of childbearing age during the use of Reduxin should use contraceptives.
Reduxin В® should not be used during breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe violations of kidney function. With caution should prescribe the drug for violations of kidneys of light and moderate severity.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe violations of liver function. With caution should be prescribed drug violations of liver function of mild and moderate severity.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
Contraindicated in the elderly over 65 years.
SPECIAL INSTRUCTIONS
Reduxin В® should be used only in those cases when all non-medicamentous measures to reduce body weight are ineffective - if the weight loss within 3 months was less than 5 kg.
Treatment Reduxin should be carried out as part of a comprehensive therapy to reduce body weight under the supervision of a doctor who has practical experience in treating obesity.
Complex therapy of obesity includes both changing diet and lifestyle, and increasing physical activity. An important component of therapy is the creation of prerequisites for a permanent change in eating habits and lifestyle that are necessary to maintain the achieved weight loss and after the abolition of drug therapy.Patients need to change their lifestyle and habits in the context of therapy with the Reduxin В® so that after the treatment is completed, the achieved weight loss is maintained. Patients should clearly realize that failure to comply with these requirements will lead to a second increase in body weight and repeated calls to the treating physician.
In patients taking Reduxin В® , it is necessary to measure blood pressure and heart rate. In the first 2 months of treatment, these parameters should be monitored every 2 weeks, and then monthly. In patients with hypertension (who have a blood pressure level above 145/90 mm Hg on the background of antihypertensive therapy), this control should be carried out especially carefully and, if necessary, at shorter intervals. In patients in whom blood pressure twice exceeded the level of 145/90 mm Hg on repeated measurement. treatment with Reduxin В® should be suspended.
Special attention should be paid to the simultaneous administration of drugs that increase the QT interval. These drugs include blockers of histamine H 1 -receptors (astemizole, terfenadine); antiarrhythmic drugs that increase the QT interval (amiodarone, quinidine, flecainide, mexiletine, propafenone, sotalol); GI motility stimulants (cisapride, pimozide, sertindole and tricyclic antidepressants). Caution should be observed when using the drug against a background of conditions that are risk factors for increasing the QT interval (hypokalemia, hypomagnesemia).
The interval between taking MAO inhibitors and Reduxin should be at least 2 weeks.
The connection between the use of Reduction and the development of primary pulmonary hypertension has not been established, but considering the generally known risk of this group of drugs, with regular medical supervision, special attention should be paid to symptoms such as progressive dyspnea (breathing disorder), chest pain and swelling of the legs.
Impact on the ability to drive vehicles and manage mechanisms
The use of Reduxin В® may limit the patient's ability to drive and manage machinery.
OVERDOSE
There are extremely limited data on the overdose of sibutramine. In case of an overdose, the patient should consult a doctor.
Symptoms: may increase the severity of side effects. Specific signs of overdose are unknown.
Treatment: reception of activated carbon, gastric lavage, symptomatic therapy, with increased blood pressure and tachycardia - the appointment of beta-blockers.There is no special treatment and no specific antidotes. It is necessary to carry out general measures: to ensure free breathing, to observe the state of the cardiovascular system, and also, if necessary, to carry out maintenance symptomatic therapy. The effectiveness of forced diuresis or hemodialysis is not established.
DRUG INTERACTION
Inhibitors of microsomal oxidation, incl. inhibitors of the 3A4 cytochrome P450 isoenzyme (including ketoconazole, erythromycin, cyclosporine) increase the plasma concentrations of sibutramine metabolites with increased heart rate and clinically insignificant increase in the QT interval. Rifampicin, macrolide antibiotics, phenytoin, carbamazepine, phenobarbital and dexamethasone can accelerate the metabolism of sibutramine. The simultaneous use of several drugs that increase serotonin levels in the blood can lead to the development of serious interaction. The so-called serotonin syndrome can develop in rare cases with the simultaneous use of Reduxin with selective serotonin reuptake inhibitors (drugs for the treatment of depression), with some drugs for the treatment of migraine (sumatriptan, dihydroergotamine), with potent analgesics (pentazocine, pethidine, fentanyl) or antitussive drugs (dextromethorphan). Sibutramine does not affect the effect of oral contraceptives.
With the simultaneous administration of sibutramine and ethanol, no increase in the negative effect of ethanol was observed. However, the use of alcohol is absolutely not compatible with the recommended dietary measures when taking sibutramine.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry place inaccessible to children at a temperature of no higher than 25 В° C. Shelf life - 3 years.
Sibutramine belongs to the list of potent substances approved by the Decree of the Government of the Russian Federation of 29.12.2007. No. 964.
