Редуксин®

General characteristics. Structure:

Active ingredient: 10 mg or 15 mg of a sibutramin of a hydrochloride of monohydrate, 153,5 mg or 158,5 mg of cellulose microcrystallic in 1 capsule.

Excipients: calcium stearate.

Structure of the capsule: titanium dioxide, dye azoruby, dye diamond blue or blue patent, gelatin.

Pharmacological properties:

Pharmacodynamics. Редуксин® - the combined drug which effect is caused by the components which are its part. Sibutramin is pro-medicine and shows the action of in vivo at the expense of metabolites (primary and secondary amines) inhibiting the return capture of monoamines (serotonin, noradrenaline and dopamine). Increase in contents in synapses of neurotransmitters increases activity of the central 5HT-serotoninovy and adrenergic receptors that promotes increase in feeling of saturation and decrease in food requirement, and also increase in thermoproducts. Indirectly activating beta3-adrenoceptors, сибутрамин influences brown fatty tissue.

Decrease in body weight is followed by increase in concentration in a blood plasma of lipoproteins of the high density (LPVP) and reduction in the amount of triglycerides, the general cholesterol, lipoproteins of the low density (LPNP) and uric acid. Sibutramin and his metabolites do not influence release of monoamines, do not inhibit a monoaminooxidase (MAO); have low affinity to a large number of neuromediator receptors, including serotoninovy (5-HT1, 5-Nt1a, 5-HT1B, 5-HT2C), adrenergic (beta1, beta2, beta3, alfa1, alfa2), dopamine (D1, D2), muskarinovy, histamine (H1), benzodiazepine and glutamate (NMDA) receptors. Cellulose microcrystallic is enterosorbents, has sorption properties and nonspecific disintoxication action.

Connects and brings out of an organism various microorganisms, products of their life activity, toxins of the exogenous and endogenous nature, allergens, xenobiotics, and also surplus of some metabolic products and metabolites responsible for development of endogenous toxicosis.

Pharmacokinetics. After intake it is quickly soaked up from the digestive tract (DT) not less than for 77%. At "primary passing" through a liver is exposed to biotransformation under the influence of CYP3A4 isoenzyme with formation of two active metabolites (монодесметилсибутрамин (M1) and дидесметилсибутрамин (Sq.m)). After reception of a single dose of 15 mg the maximum concentration in a blood plasma (Cmax) M1 makes 4 ng/ml (3,2-4,8 ng/ml), Sq.m — 6,4 ng/ml (5,6-7,2 ng/ml). Cmax is reached in 1,2 h (сибутрамин), 3-4 h (M1 and Sq.m). The concomitant use of food lowers Cmax of metabolites for 30% and increases time of its achievement for 3 h, without changing the area under a curve "concentration time" (AUC).

It is quickly distributed on fabrics. Communication with proteins makes 97% (сибутрамин) and 94% (M1 and Sq.m). Equilibrium concentration of active metabolites in a blood plasma is reached within 4 days after the beginning of use and turns concentration in a blood plasma approximately twice after reception of a single dose. An elimination half-life of a sibutramin - 1,1 h, M1 - 14 h, Sq.m - 16 h. Active metabolites are exposed to a hydroxylation and conjugation with formation of inactive metabolites which are removed preferential by kidneys.

The limited data which are available now do not indicate existence of clinically significant distinctions in pharmacokinetics at men and women.

The pharmacokinetics at elderly healthy faces (average age of 70 years) is similar that at young people.

Renal failure. The renal failure has no effect on AUC of active metabolites M1 and Sq.m, except the Sq.m metabolite at the patients with an end-stage of a renal failure who are on dialysis.

Liver failure. Patients with a moderate liver failure after a single dose have a sibutramina of AUC of active metabolites of M1 and Sq.m 24% higher, than at healthy faces.

Indications to use:

Редуксин® it is shown for decrease in body weight at the following states:
• alimentary obesity with the body weight index (BWI) of 30 kg/sq.m and more;
• alimentary obesity with an index of the body weight of 27 kg/sq.m and more in combination with a diabetes mellitus 2 types and a dislipidemiya.

Route of administration and doses:

Редуксин® is accepted in 1 times a day. The dose is established individually, depending on portability and clinical performance.

The initial dose of 10 mg/days is recommended, at bad portability reception of 5 mg/days is possible. Capsules should be accepted in the morning, without chewing and washing down with enough liquid (a glass of water). Drug can be accepted as on an empty stomach, and to combine with meal. If within 4 weeks from an initiation of treatment decrease in body weight less than 2 kg is not reached, then the dose increases to 15 mg/days.

Treatment by the drug Reduksin® should not continue more than 3 months at patients who insufficiently well react to therapy i.e. which within 3 months of treatment do not manage to reach decrease in body weight by 5% of an initial indicator.

Treatment should not be continued if at further therapy, after the reached decrease in body weight, the patient adds in the body weight of 3 kg and more again. Duration of treatment should not exceed 1 years as concerning more long period of reception of a sibutramin data on efficiency and safety are absent.

Treatment by the drug Reduksin® has to be performed in a complex with a diet and physical exercises under control of the doctor having practical experience of treatment of obesity.

Features of use:

Use during pregnancy and breastfeeding. As so far there is no rather large number of researches concerning safety of impact of a sibutramin on a fruit, this drug is contraindicated during pregnancy. The women who are in reproductive age during administration of drug of Reduksin® have to use contraceptive means. It is contraindicated to accept Reduksin® during breastfeeding.

Редуксин® it is necessary to apply only when all non-drug actions for decrease in body weight are ineffective - if decrease in body weight within 3 months made less than 5 kg.

Treatment by the drug Reduksin® has to be performed within complex therapy on decrease in body weight under control of the doctor having practical experience of treatment of obesity. Complex therapy includes both change of a diet and a way of life, and increase in physical activity. An important component of therapy is creation of premises to permanent change of a feeding behavior and a way of life which are necessary for preservation of the reached decrease in body weight and after cancellation of medicamentous therapy. Patients need to change within therapy by the drug Reduksin® the way of life and habits so that after completion of treatment to provide preservation of the reached body degrowth.

Patients have to have a clear view that non-compliance with these requirements will lead to repeated increase in body weight and repeated addresses to the attending physician. At the patients accepting Reduksin® it is necessary to measure the arterial pressure and heart rate regularly. In the first 3 months of treatment it is necessary to control these parameters each 2 weeks, and then monthly. If during two visits increase in heart rate at rest of ≥10 beats per minute or the systolic/diastolic pressure of ≥10 mm hg in a row comes to light, it is necessary to stop treatment.

At patients with arterial hypertension at whom against the background of hypotensive therapy arterial pressure is higher than 145/90 mm hg this control has to be carried out especially carefully and, if necessary, through shorter intervals. At patients at whom arterial pressure twice at repeated measurement exceeded the level of 145/90 mm hg treatment by the drug Reduksin® has to be cancelled (See the section "Side effect").

At patients with an apnoea syndrome in a dream it is necessary to control arterial pressure especially carefully.

The special attention is required by co-administration of the drugs increasing QT interval. Treat these drugs H1-gistaminoblokatory (астемизол, терфенадин); the antiarrhytmic drugs increasing QT interval (Amiodaronum, quinidine, флекаинид, мексилетин, пропафенон, соталол); stimulator of motility of a gastrofinal path цизаприд; Pimozidum, сертиндол and tricyclic antidepressants. It concerns also states which are capable to lead to increase in an interval of QT, such as, a hypopotassemia and a hypomagnesiemia. (See also section "Interaction with Other Medicines").

The interval between reception of MAO inhibitors (including furasolidone, Procarbazinum, a selegilin) and the drug Reduksin® has to make not less than 2 weeks.

Though connection between administration of drug of Reduksin® and development of primary pulmonary hypertensia is not established, however, considering well-known risk of drugs of this group, at regular medical control it is necessary to pay special attention to such symptoms as progressing диспноэ (breath disturbance), thorax pain and hypostases standing.

At the admission of a dose of the drug Reduksin® it is not necessary to accept a double dose of drug in the following reception, it is recommended to continue further administration of drug according to the ordered scheme.

Duration of administration of drug of Reduksin® should not exceed 1 years.

At joint reception of a sibutramin and other inhibitors of the return serotonin reuptake there is an increased risk of development of bleedings. At the patients predisposed to bleedings, and also accepting the drugs influencing a hemostasis or function of thrombocytes сибутрамин it is necessary to apply with care.

Though clinical data on accustoming to a sibutramin are absent, it is necessary to find out whether was in the anamnesis of the patient of cases of medicinal dependence and to pay attention to possible signs of abuse of medicines.

Influence on ability to control of vehicles and mechanisms. Administration of drug of Reduksin® can limit ability to control of vehicles and mechanisms. During use of the drug Reduksin® it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Most often side effects arise in an initiation of treatment (in the first 4 weeks). Their expressiveness and frequency weaken eventually. Side effects carry, in general, not difficult and reversible difficult character. Side effects, depending on impact on bodies and systems of bodies, are presented in the following order: very often (> 10%), it is frequent (≥ 1%, but ≤ 10%).

From the central nervous system very frequent side effects are dryness in a mouth and sleeplessness, the headache, dizziness, concern, paresthesias, and also taste change are often noted.

From cardiovascular system tachycardia, a heart consciousness, increase in arterial pressure, a vazodilatation often meet.

From system of digestive organs loss of appetite and a lock, often nausea and an exacerbation of hemorrhoids are very often observed. At tendency to locks in the first days control of evakuatorny function of intestines is necessary. At emergence of a lock reception is stopped and accept laxative.

From integuments the increased sweating is often noted. In isolated cases at treatment sibutraminy the following undesirable clinically significant phenomena are described: a dysmenorrhea, hypostases, a grippopodobny syndrome, a skin itch, a dorsodynia, an abdominal pain, paradoxical increase in appetite, thirst, rhinitis, a depression, drowsiness, emotional lability, uneasiness, irritability, nervousness, acute intersticial nephrite, bleedings, Shenleyn-Genokh's purpura (hemorrhages in skin), spasms, thrombocytopenia, tranzitorny increase in activity of "hepatic" enzymes in blood.

Changes of cardiovascular system. Moderate rise in arterial pressure at rest upon 1 - 3 mm hg and moderate increase in pulse by 3 - 7 beats per minute is observed. In some cases more expressed increases in arterial pressure and heart rate are not excluded. Clinically significant changes of arterial pressure and pulse are registered preferential in an initiation of treatment (in the first 4 - 8 weeks).

Use of the drug Reduksin® for patients with the increased arterial pressure: watch the section "Contraindications" and "Special Instructions". During the post-market researches the additional side reactions which are listed below on systems of bodies were described:

From cardiovascular system: ciliary arrhythmia.

From immune system: hypersensitivity reactions (from a moderate enanthesis and a small tortoiseshell to a Quincke's disease (Quincke's edema) and an anaphylaxis).

Mental disorders: psychosis, states suitsidalno the directed thinking, a suicide and a mania. At emergence of similar states drug needs to be cancelled.

From a nervous system: spasms, short-term disturbances of memory.

From an organ of sight: sight misting ("veil before eyes").

From system of digestive organs: diarrhea, vomiting.

From skin and hypodermic cellulose: alopecia.

From kidneys and urinary tract: ischuria.

From reproductive system: disturbances of an ejaculation/orgasm, impotence, disturbance of a menstrual cycle, uterine bleedings.

Interaction with other medicines:

Inhibitors of a microsomal oxidation, including CYP3A4 isoenzyme inhibitors (кетоконазол, erythromycin, cyclosporine, etc.) raise in a blood plasma of concentration of metabolites of a sibutramin with increase in heart rate and clinically insignificant increase in an interval of QT. Rifampicin, antibiotics from group of macroleads, Phenytoinum, carbamazepine, phenobarbital and dexamethasone can accelerate metabolism of a sibutramin.

Simultaneous use of several drugs increasing the content of serotonin in a blood plasma can lead to development of serious interaction. The so-called serotoninovy syndrome can develop in rare instances at simultaneous use of the drug Reduksin® with selective serotonin reuptake inhibitors (drugs for treatment of a depression), with some drugs for treatment of migraine (суматриптан, dihydroergotamine), with strong analgetics (pentazocine, pethidine, fentanyl), or antibechic drugs (dextromethorphan).

Sibutramin does not influence action of peroral contraceptive means.

At a concomitant use of a sibutramin and alcohol strengthening of negative effect of alcohol was not noted. However alcohol is not combined with the dietary actions recommended at reception of a sibutramin at all.

At simultaneous use with sibutraminy other drugs influencing a hemostasis or function of thrombocytes the risk of development of bleedings increases.

Medicinal interaction at simultaneous use of a sibutramin with the drugs increasing the arterial pressure and heart rate is insufficiently fully studied now. This group of drugs includes decongestants, antibechic, anti-cold and antiallergic drugs which part ephedrine or pseudoephedrine are. Therefore in cases of a concomitant use of these drugs with sibutraminy it is necessary to be careful.

Combined use of a sibutramin with the drugs for decrease in body weight operating on the central nervous system or drugs for treatment of mental disorders contraindicated.

Contraindications:

- the established hypersensitivity to a sibutramin or to other components of drug;
- existence of the organic reasons of obesity (for example, hypothyroidism);
- serious violations of food — nervous anorexia or nervous bulimia;
- mental diseases;
- syndrome Gilles de la Turetta (generalized tics);
- a concomitant use of MAO inhibitors (for example, phentermine, a fenfluramin, a deksfenfluramin, ethylamphetamine, ephedrine) or use within 2 weeks before administration of drug of Reduksin® and 2 weeks after the end of its reception of other drugs operating on the central nervous system, inhibiting the return serotonin reuptake (for example, antidepressants, neuroleptics); the somnolent drugs containing tryptophane and also other drugs of the central action for decrease in body weight or for treatment of mental disorders;
- cardiovascular diseases (in the anamnesis and now): coronary heart disease (myocardial infarction (MI), stenocardia); chronic heart failure in decompensation stages, okklyuziruyushchy diseases of peripheral arteries, tachycardia, arrhythmia, cerebrovascular diseases (a stroke, tranzitorny disturbances of cerebral circulation);
- uncontrollable arterial hypertension (the arterial pressure (AP) is higher than 145/90 mm hg) (see also section "Special Instructions");
- thyrotoxicosis;
- heavy abnormal liver functions and/or kidneys;
- benign hyperplasia of a prostate;
- pheochromocytoma;
- closed-angle glaucoma;
- the established pharmacological, drug or alcohol addiction;
- pregnancy and period of breastfeeding;
- the age up to 18 years is also more senior than 65 years.

With care it is necessary to appoint drug at the following states: arrhythmias in the anamnesis, chronic insufficiency blood circulation, diseases of coronary arteries (including in the anamnesis), except coronary heart disease (to THEM, stenocardia); to glaucoma, except closed-angle glaucoma, a cholelithiasis, arterial hypertension (controlled and in the anamnesis), neurologic disturbances, including a delay of intellectual development and a spasm (including in the anamnesis), epilepsy, an abnormal liver function and/or kidneys easy and moderate severity, motor and verbal tics in the anamnesis, tendency to bleeding, disturbance of coagulability of blood, the administration of drugs influencing a hemostasis or function of thrombocytes.

Overdose:

There are extremely limited data on an occasion of overdose of a sibutramin. The most often found adverse reactions connected with overdose: tachycardia, increase in arterial pressure, headache, dizziness. It is necessary to inform the attending physician in case of alleged overdose.

Special treatment and specific antidotes does not exist. It is necessary to carry out the general actions: to provide free breath, to watch a condition of cardiovascular system, and also, if necessary, to perform the supporting symptomatic therapy. Timely use of absorbent carbon, and also a gastric lavage can reduce receipt of a sibutramin in an organism.

Patients with the increased arterial pressure and tachycardia can appoint beta adrenoblockers. Efficiency of an artificial diuresis or hemodialysis is not established.

Storage conditions:

In the place protected from light at a temperature not above 25 °C. Drug should be stored in the places unavailable to children. Sibutramin treats the List of strong substances approved by the Resolution of the Government of the Russian Federation of 29.12.2007 No. 964. A period of validity - 3 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Firm gelatin capsules. On 7, 10, 14 or 15 capsules in a blister strip packaging from the film of PVC and printing aluminum foil varnished. 1, 2, 3, 4, 6, 8, 9,10, 12, 15, 16, 18 or 20 blister strip packagings together with the application instruction place in a pack from a cardboard.