Reduxin - instructions for use, dose, side effects, contraindications

Active substanceSibutramine + Microcrystalline celluloseSibutramine + Microcrystalline cellulose

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Reduxin®

capsules inwards

Promomed Rus, Open Company Russia

Dosage form: & nbspCapsules.

Composition:

Composition per 1 capsule for dosage of 10 mg +158.5 mg:

Active substances:

Sibutramine hydrochloride monohydrate - 10 mg; cellulose microcrystalline - 158.5 mg

Excipients:

Calcium stearate - 1.5 mg

Capsule composition: titanium dioxide - 2.0000%, dye azorubin - 0.0041 %, the dye is brilliant blue - 0.0441%, gelatin - up to 100%.

Composition per 1 capsule for dosage of 15 mg + 153.5 mg:

Active substances:

Sibutramine hydrochloride monohydrate - 15 mg; cellulose microcrystalline - 153.5 mg

Excipients:

Calcium stearate - 1.5 mg

Capsule composition: titanium dioxide - 2.0000 %, dye blue patented - 0.2737%, gelatin - up to 100%.

Description:Capsules number 2 of blue color for a dosage of 10 mg + 158.5 mg or blue for a dosage of 15 mg + 153.5 mg. The contents of the capsules are white or white powder with a slightly yellowish hue.

Pharmacotherapeutic group:Means for treating obesity

ATX: & nbsp

A.08.A.A Preparations for the treatment of centralized obesity

Pharmacodynamics:Reduxin® is a combined preparation, the effect of which is due to its constituent components. Sibutramine is a prodrug and exerts its effect through metabolites (primary and secondary amines) inhibiting the reuptake of monoamines (serotonin, norepinephrine and dopamine).An increase in the content of neurotransmitters in the synapses increases the activity of central 5HT-serotonin and adrenergic receptors, which contributes to an increase in satiety and a decrease in the need for food, as well as an increase in thermal production. By indirectly activating beta3-adrenergic receptors, sibutramine affects the brown adipose tissue. The decrease in body weight is accompanied by an increase in plasma concentrations of high-density lipoprotein (HDL) and a decrease in triglycerides, total cholesterol, low-density lipoprotein (LDL), and uric acid. Sibutramine and its metabolites do not affect the release of monoamines, do not inhibit monoamine oxidase (MAO); have low affinity for a large number of neurotransmitter receptors, including serotonin (5-HT₁, 5HT_1A, 5-H_1B, 5-HT_2C), adrenergic (beta₁, beta₂, beta₃, alpha₁, alpha₂), dopamine (D₁, D₂), muscarinic, histamine (H₁), benzodiazepine and glutamate (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:

After oral administration, it is rapidly absorbed from the gastrointestinal tract (GIT) by at least 77%. At the "primary passage" through the liver is subjected to biotransformation under the influence of isoenzyme CYP3A4 with the formation of two active metabolites (monodesmethylsibutramine (M1) and didesmethylsibutramine (M2)). After taking a single dose of 15 mg, the maximum concentration in the blood plasma (C_max) M1 is 4 ng / ml (3.2-4.8 ng / ml), M2 - 6.4 ng / ml (5.6-7.2 ng / ml). FROM_max achieved after 1.2 hours (sibutramine), 3-4 hours (M1 and M2). Simultaneous food intake lowers C_maxmetabolites by 30% and increases the time of its achievement by 3 hours, without changing the area under the curve "concentration-time" (AUC). Quickly distributed to tissues. The connection with proteins is 97% (sibutramine) and 94 % (M1 and M2). The equilibrium concentration of active metabolites in blood plasma is reached within 4 days after the beginning of application and approximately 2 times higher than the concentration in the blood plasma after taking a single dose. The half-life of sibutramine is 1.1 hours, M1 - 14 hours, M2 -16 hours.Active metabolites undergo hydroxylation and conjugation with the formation of inactive metabolites, which are excreted mainly by the kidneys.

Currently available limited data do not indicate the existence of clinically significant differences in pharmacokinetics in men and women.

Pharmacokinetics in elderly healthy individuals (mean age 70 years) is similar to that in young adults.

Renal insufficiency

Renal failure does not affect AUC active metabolites M1 and M2, in addition to the M2 metabolite in patients with terminal stage of renal failure who are on dialysis.

Liver failure

In patients with moderate hepatic insufficiency after a single intake of sibutramine AUC active metabolites M1 and M2 is 24% higher than in healthy individuals.

Indications:

Reduxin® is indicated for weight loss under the following conditions:

alimentary obesity with body mass index (BMI) of 30 kg / m² and more;
alimentary obesity with a body mass index of 27 kg / m² and more in combination with type 2 diabetes and dyslipidemia.

Contraindications:

- established hypersensitivity to sibutramine or to other components of the drug;

- the presence of organic causes of obesity (eg, hypothyroidism);

- severe eating disorders - anorexia nervosa or bulimia nervosa;

- mental illness;

- Gilles de la Tourette syndrome (generalized tics);

- simultaneous administration of MAO inhibitors (eg, phentermine, fenfluramine, dexfenfluramine, ethylamphetamine, ephedrine) or 2 weeks prior to taking Reduxin® and 2 weeks after the end of its intake of other drugs acting on the central nervous system that inhibit serotonin reuptake (for example , antidepressants, neuroleptics); hypnotics containing tryptophan, as well as other drugs of central action for weight loss or for the treatment of mental disorders;

- cardiovascular diseases (in the anamnesis and now): ischemic heart disease (myocardial infarction (MI), angina pectoris); chronic heart failure in the stage of decompensation, occlusive diseases of peripheral arteries, tachycardia, arrhythmia, cerebrovascular diseases (stroke, transient disorders of cerebral circulation);

- uncontrolled arterial hypertension (blood pressure (BP) above 145/90 mmHg)See also "Special instructions");

- thyrotoxicosis;

- severe dysfunction of the liver and / or kidney;

- benign prostatic hyperplasia;

- pheochromocytoma;

- angle-closure glaucoma;

- established pharmacological, narcotic or alcohol dependence;

- pregnancy and the period of breastfeeding;

- age is 18 years and over 65 years.

Carefully:

Carefully should prescribe the drug in the following conditions: arrhythmia in history, chronic circulatory failure, coronary artery disease (including history), in addition to coronary heart disease (myocardial infarction, angina pectoris); glaucoma, except for closed-angle glaucoma, cholelithiasis, arterial hypertension (controlled and in anamnesis), neurological disorders, including mental retardation and convulsions (including in history), epilepsy, impaired liver function and / or kidneys of mild and moderate severity, motor and verbal tics in the anamnesis, a tendency to bleeding, a violation of blood clotting, the intake of drugs that affect hemostasis or platelet function.

Pregnancy and lactation:

Since there is not a sufficiently large amount of research to date regarding the safety of sibutramine exposure to fetus, this drug is contraindicated during pregnancy. Women who are of reproductive age should use contraceptives while taking Reduxin®.

It is contraindicated to take Reduxin® during breastfeeding.

Dosing and Administration:

Reduxin® is taken orally once a day. The dose is set individually, depending on the tolerability and clinical effectiveness.

An initial dose of 10 mg / day is recommended, with a poor tolerance of 5 mg / day. Capsules should be taken in the morning without chewing and drinking with a sufficient amount of liquid (a glass of water). The drug can be taken as an empty stomach or combined with a meal. If within 4 weeks from the beginning of treatment there is no reduction in body weight less than 2 kg, the dose increases to 15 mg / day. Treatment with Reduxin® should not last more than 3 months in patients who do not respond well enough to therapy, i.e.who during the 3 months of treatment can not achieve a reduction in body weight by 5% of the baseline. Treatment should not be continued if, in further therapy, after the body weight reduction is achieved, the patient again adds 3 kg or more in the body mass. Duration of treatment should not exceed 1 year, since there is no data on efficacy and safety for a longer period of sibutramine intake. Treatment with Reduxin® should be carried out in combination with diet and exercise under the supervision of a doctor who has practical experience in the treatment of obesity.

Side effects:

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. Side effects, depending on the effect on organs and organ systems, are presented in the following order: very often (> 10%), often (≥ 1%, but ≤ 10 %).

From the side of the central nervous system, very frequent side effects are dry mouth and insomnia, headache, dizziness, anxiety, paresthesia, and taste change are often noted.

On the part of the cardiovascular system, tachycardia, palpitations, increased blood pressure, and vasodilatation are common.

On the part of the digestive system, loss of appetite and constipation are often observed, often nausea and 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.

From the side of the skin is often marked sweating.

In single cases, the following undesirable clinically significant events are described in the treatment of sibutramine: dysmenorrhea, edema, flu-like syndrome, skin itching, back pain, abdominal pain, paradoxical appetite increase, thirst, rhinitis, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, acute interstitial nephritis, bleeding, purpura Shenlen-Henoch (hemorrhages in the skin), convulsions, thrombocytopenia, transient increase in the activity of "hepatic" enzymes in the blood. Changes in the cardiovascular system. 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 are registered mainly at the beginning of treatment (in the first 4-8 weeks).

Application of the drug Reduxin® in patients with high blood pressure: see the section "Contraindications" and "Special instructions".

Post-marketing studies described additional side reactions listed below in organ systems:

From the cardiovascular system: atrial fibrillation.

From the immune system: hypersensitivity reactions (from moderate rashes on the skin and urticaria to angioedema (Quincke's edema) and anaphylaxis).

Mental disorders: psychosis, the state of suicidal thinking, suicide and mania. If such conditions occur, the drug should be discarded.

From the nervous system: cramps, short-term memory impairment.

From the side of the organ of vision: blurring of vision ("veil before the eyes").

On the part of the digestive system: diarrhea, vomiting.

From the skin and subcutaneous tissue: alopecia.

From the side of the kidneys and urinary tract: retention of urine.

On the part of the reproductive system: impaired ejaculation / orgasm, impotence, menstrual irregularity, uterine bleeding.

Overdose:There are extremely limited data on the overdose of sibutramine. The most common adverse reactions associated with overdose: tachycardia, increased blood pressure, headache, dizziness. You should notify your doctor if there is an alleged overdose.

Special treatment and specific antidotes do not exist. 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 supporting symptomatic therapy. Timely application activated charcoal, as well as gastric lavage can reduce the intake of sibutramine in the body. Patients with high blood pressure and tachycardia can be assigned beta-blockers. The effectiveness of forced diuresis or hemodialysis is not established.

Interaction:

Inhibitors of microsomal oxidation, including inhibitors of the isoenzyme CYP3 A4 (ketoconazole, erythromycin, ciclosporin , etc.) increase the plasma concentrations of sibutramine metabolites with an increase in the heart rate and clinically insignificant increase in the QT interval. Rifampicin, antibiotics from the macrolide group, phenytoin, carbamazepine, phenobarbital and dexamethasone can accelerate the metabolism of sibutramine. The simultaneous use of several drugs that increase serotonin levels in blood plasma can lead to the development of serious interaction. The so-called serotonin syndrome can develop in rare cases with simultaneous application of the Reduxin® preparation with selective serotonin reuptake inhibitors (drugs for the treatment of depression), with some medications 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 alcohol, there was no increase in the negative effect of alcohol.However, alcohol is absolutely not compatible with the recommended dietary measures when taking sibutramine.

With the simultaneous use with sibutramine other drugs that affect hemostasis or platelet function, the risk of bleeding increases. The drug interaction with the simultaneous use of sibutramine with drugs that increase blood pressure and heart rate, is currently not fully understood. This group of drugs includes decongestants, antitussives, anti-catarrhal and antiallergic drugs, which include ephedrine or pseudoephedrine. Therefore, in cases of simultaneous administration of these drugs with sibutramine, care should be taken. Joint use of sibutramine with medications to reduce body weight, acting on the central nervous system, or drugs for the treatment of mental disorders is contraindicated.

Special instructions:

Reduxin® should be used only in cases when all non-medicamentous measures to reduce body weight are ineffective - if the reduction in body weight within 3 months was less than 5 kg.Treatment with the drug Reduxin® should be carried out within the framework of complex therapy for weight loss under the supervision of a doctor who has practical experience in the treatment of obesity. Complex therapy includes both changing diet and lifestyle, and increasing physical activity. An important component of therapy is the creation of the prerequisites for a persistent change in eating behavior 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 within the framework of therapy with the Reduxin® preparation in such a way that after the completion of treatment it is ensured that the achieved reduction in body weight 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®, it is necessary to regularly check blood pressure and heart rate. In the first 3 months of treatment, these parameters should be monitored every 2 weeks, and then monthly. If, during two visits in a row, there is an increase in the heart rate at rest ≥ 10 beats per minute or systolic / diastolic pressure ≥ 10 mm Hg, it is necessary to stop treatment. In patients with hypertension who have arterial blood pressure above 145/90 mm Hg on the background of antihypertensive therapy, this control should be carried out particularly carefully and, if necessary, at shorter intervals. In patients who have twice the arterial blood pressure at a repeated measurement of 145/90 mm Hg, the treatment with Reduxin® should be reversed (see the "Side effect" section).

Patients with sleep apnea syndrome need to carefully monitor blood pressure.

Special attention should be paid to the simultaneous administration of drugs that increase the QT interval. These drugs include H1-histamin blockers (astemizole, terfenadine); antiarrhythmic drugs that increase the QT interval (amiodarone, quinidine, flecainide, mexiletine, propafenone, sotalol); stimulator of gastrointestinal motility of cisapride; pimozide, sertindole and tricyclic antidepressants. This also applies to conditions that can lead to an increase in the QT interval, such as hypokalemia and hypomagnesemia (see Fig.(see also the section "Interaction with other drugs").

The interval between the intake of MAO inhibitors (including furazolidone, procarbazine, selegiline) and the Reduxin® preparation should be at least 2 weeks.

Although the relationship between taking Reduxin® and the development of primary pulmonary hypertension has not been established, however, given the generally known risk of this group of drugs, with regular medical supervision, special attention should be paid to symptoms such as progressive dyspnea, chest pain and swelling on foot.

If you miss a dose of Reduxin®, you should not take a double dose of the drug in the next dose, it is recommended that you continue taking the drug again according to the prescribed schedule.

The duration of taking Reduxin® should not exceed 1 year.

With the joint administration of sibutramine and other serotonin reuptake inhibitors, there is an increased risk of bleeding. In patients who are prone to bleeding, as well as taking drugs that affect hemostasis or platelet function, sibutramine should be used with caution.

Although clinical data on addiction to sibutramine are not available, it should be ascertained whether there has been a history of drug dependence in the patient's history and pay attention to possible signs of drug abuse.

Effect on the ability to drive transp. cf. and fur:

The use of Reduxin® may limit the ability to drive vehicles and mechanisms. During the period of use of the Reduxin® preparation, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:Capsules 10 mg + 158.5 mg; capsules 15 mg + 153.5 mg.

Packaging:By 7, 10, 14 or 15 capsules in a contour mesh box made of PVC film and foil of aluminum printed lacquered.
When manufacturing at OOO OZON:
By 7, 10, 14, 15, 28, 30, 60, 90, 120, 150, 160 or 180 capsules per container polymer for medicinal purposes means. One container or 1, 2, 3, 4, 6, 8, 9, 10, 12, 15, 16, 18 or 20 contour cell packs together with instructions for use put in a pack of cardboard.
When manufacturing at FSUE "Moscow Endocrine Plant":
1, 2, 3, 4, 6, 8, 9,10, 12, 15, 16, 18 or 20 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:In a dry place at a temperature of not more than + 25 ° C.
Keep out of the reach of children.

Shelf life:3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-002110

Date of registration:18.02.2013

The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp05.10.2015

Illustrated instructions

Instructions

Reduxin® (Reduxin® )