REDUXIN 15mg+153.5 mg

Pharmacodynamics

Reduksin® is a combined preparation, the action of which is due to its constituent components.

Sibutramine is a prodrug and exerts its effect in vivo through metabolites (primary and secondary amines) that inhibit the reuptake of monoamines (serotonin, norepinephrine and dopamine). An increase in the content of neurotransmitters in synapses increases the activity of central 5HT-serotonin and adrenergic receptors, which contributes to an increase in the feeling of satiety and a decrease in the need for food, as well as an increase in thermal production. By indirectly activating beta3-adrenergic receptors, sibutramine acts on brown adipose tissue. The decrease in body weight is accompanied by an increase in the concentration of HDL in the blood plasma and a decrease in the amount of triglycerides, total cholesterol, LDL and uric acid. Sibutramine and its metabolites do not affect the release of monoamines, do not inhibit MAO; possess low affinity for a large number of neurotransmitter receptors, including serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2C), adrenergic (beta1-, beta2-, beta3-, alpha1-, alpha2-), dopamine (D1 , D2), muscarinic, histamine (H1), benzodiazepine and glutamate (NMDA) receptors.

Microcrystalline cellulose is an enterosorbent, has sorption properties and a nonspecific detoxification effect. It binds and removes from the body various microorganisms, their metabolic products, 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 by at least 77%. During the initial passage through the liver, it undergoes biotransformation under the influence of the isoenzyme CYP3A4 with the formation of two active metabolites - monodesmethylsibutramine (M1) and didesmethylsibutramine (M2). After taking a single dose of 15 mg Cmax in blood plasma M1 is 4 ng / ml (3.2-4.8 ng / ml), M2-6.4 ng / ml (5.6-7.2 ng / ml). Cmax is achieved after 1.2 hours (sibutramine), 3-4 hours (M1 and M2). Simultaneous food intake lowers the Cmax of metabolites by 30% and increases the time to reach it by 3 hours without changing the AUC. Distributes quickly to tissues. The connection with proteins is 97% (sibutramine) and 94% (M1 and M2). Css of active metabolites in blood plasma is reached within 4 days after the start of use and is approximately 2 times higher than the concentration in blood plasma after taking a single dose. T1 / 2 of sibutramine - 1.1 hours, M1 - 14 hours, M2 - 16 hours. Active metabolites undergo hydroxylation and conjugation to form inactive metabolites, which are excreted mainly by the kidneys.

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

Pharmacokinetics in elderly healthy individuals (average age - 70 years) is similar to that in young people.

Renal failure

Renal failure has no effect on the AUC of active metabolites M1 and M2, except for the M2 metabolite in patients with end-stage renal failure on dialysis.

Liver failure

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

Reduksin: Indications

Reduksin® is indicated for weight loss in the following conditions:

alimentary obesity with a body mass index (BMI) of 30 kg / m2 or more;

alimentary obesity with a BMI of 27 kg / m2 or more in combination with type 2 diabetes mellitus and dyslipidemia.

Method of administration and dosage

Inside, 1 time per day, in the morning, without chewing and drinking enough liquid (a glass of water). The drug can be taken both on an empty stomach and combined with meals.

The dose is set individually, depending on the tolerability and clinical efficacy. The recommended initial dose is 10 mg, with poor tolerance, 5 mg may be taken. If, within 4 weeks from the start of treatment, a decrease in body weight of less than 2 kg is achieved, then the dose is increased to 15 mg / day.

Treatment with Reduxin® should not be continued for more than 3 months in patients who do not respond well to therapy, i.e. who, within 3 months of treatment, fail to achieve a decrease in body weight by 5% from the initial indicator. Treatment should not be continued if, with further therapy, after the achieved weight loss, the patient's body weight increases by 3 kg or more.

The duration of treatment should not exceed 1 year, since there are no data on efficacy and safety for a longer period of taking sibutramine.

Treatment with Reduksin® should be carried out in combination with diet and exercise under the supervision of a physician with practical experience in the treatment of obesity.

Application during pregnancy and lactation

Since until now there is not a sufficiently large number of studies regarding the safety of the effects of sibutramine on the 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® while breastfeeding.

Reduksin: Contraindications

established hypersensitivity to sibutramine or other components of the drug;

the presence of organic causes of obesity (for example, hypothyroidism);

severe eating disorders (anorexia nervosa or bulimia nervosa);

mental illness;

Gilles de la Tourette's syndrome (generalized tics);

simultaneous administration of MAO inhibitors (for example, phentermine, fenfluramine, dexfenfluramine, ethylamphetamine, ephedrine) or their use within 2 weeks before taking the drug Reduxin® and 2 weeks after the end of its administration; other drugs that act on the central nervous system that inhibit serotonin reuptake (for example, antidepressants), antipsychotics, hypnotics containing tryptophan, as well as other centrally acting drugs for weight loss or for the treatment of mental disorders;

cardiovascular diseases (in history and at present): ischemic heart disease (myocardial infarction (MI), angina pectoris); chronic heart failure in the stage of decompensation, occlusive disease of peripheral arteries, tachycardia, arrhythmia, cerebrovascular diseases (stroke, transient cerebrovascular accident);

uncontrolled arterial hypertension (blood pressure above 145/90 mm Hg - see also "Special instructions");

thyrotoxicosis; impairment of liver and / or kidney function;

benign prostatic hyperplasia;

pheochromocytoma;

angle-closure glaucoma;

established pharmacological, drug or alcohol dependence;

pregnancy;

lactation period;

age under 18 and over 65.

With care: history of arrhythmia, chronic circulatory failure, coronary artery disease (including history), except for coronary heart disease (MI, angina pectoris); glaucoma, except for angle-closure glaucoma, cholelithiasis, arterial hypertension (controlled and in history), neurological disorders, including mental retardation and seizures (including in history), epilepsy, impaired liver and / or kidney function of mild to moderate severity , a history of motor and verbal tics, a tendency to bleeding, bleeding disorders, taking drugs that affect hemostasis or platelet function.

Reduksin: 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 mild 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 often - dry mouth and insomnia; often - headache, dizziness, anxiety, paresthesia, and taste changes.

From the CVS: often - tachycardia, palpitations, increased blood pressure, vasodilation.

There is a moderate rise in blood pressure at rest by 1–3 mm Hg. Art. and a moderate increase in heart rate by 3–7 beats / min. In some cases, more pronounced increases in blood pressure and heart rate are not excluded. Clinically significant changes in blood pressure and heart rate are recorded mainly at the beginning of treatment (in the first 4–8 weeks).

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

On the part of the digestive system: very often - loss of appetite and constipation, often - nausea and exacerbation of hemorrhoids. With a tendency to constipation in the early days, it is necessary to control the evacuation function of the intestine. If constipation occurs, they stop taking and take a laxative.

From the side of the skin: often - increased sweating. In isolated cases, during treatment with sibutramine, the following undesirable clinically significant phenomena are described: dysmenorrhea, edema, flu-like syndrome, itching of the skin, back pain, abdominal pain, paradoxical increase in appetite, thirst, rhinitis, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, acute interstitial nephritis, bleeding, Shenlein-Henoch purpura (bleeding into the skin), convulsions, thrombocytopenia, transient increase in the activity of liver enzymes in the blood.

In the course of post-marketing studies, additional adverse reactions, listed below, have been described for organ systems:

From the CCC side: atrial fibrillation.

From the immune system: hypersensitivity reactions (from mild skin rashes and urticaria to angioedema (angioedema) and anaphylaxis).

Mental disorders: psychosis, states of suicidal thinking, suicide and mania. When such problems occur

Interaction

Microsomal oxidation inhibitors, incl. inhibitors of the isoenzyme CYP3A4 (including ketoconazole, erythromycin, cyclosporin), increase the plasma concentration of sibutramine metabolites with an increase in heart rate and a 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 the level of serotonin in the blood plasma can lead to the development of a serious interaction. In rare cases, with the simultaneous use of the drug Reduxin® with SSRIs (drugs for the treatment of depression), some drugs for the treatment of migraines (sumatriptan, dihydroergotamine), potent analgesics (pentazocine, pethidine, fentanyl) or antitussive drugs (dextromethorphan) may develop so-called. serotonin syndrome.

Sibutramine does not interfere with 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 combined with the dietary measures recommended when taking sibutramine.

With the simultaneous use of other drugs with sibutramine 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-cold and antiallergic drugs, which include ephedrine or pseudoephedrine. Therefore, in cases of concomitant use of these drugs with sibutramine, caution should be exercised. The concomitant use of sibutramine with drugs for weight loss, acting on the central nervous system, or drugs for the treatment of mental disorders is contraindicated.

special instructions

Reduksin® should be used only in cases where all non-drug measures to reduce body weight are ineffective - if the decrease in body weight within 3 months was less than 5 kg.

Treatment with Reduxin® should be carried out as part of a complex therapy for weight loss under the supervision of a physician with practical experience in the treatment of obesity.

Complex therapy includes changes in diet and lifestyle, as well as increased physical activity.

An important component of therapy is the creation of the prerequisites for persistent changes in eating behavior and lifestyle, which are necessary to maintain the achieved weight loss even after drug therapy is discontinued. Patients need to change their lifestyle and habits within the framework of therapy with Reduksin® in such a way as to ensure that the achieved weight loss is maintained after the completion of treatment.

Patients must clearly understand that non-compliance with these requirements will lead to repeated weight gain and repeated visits to the attending physician.

In patients taking Reduxin®, blood pressure and heart rate should be measured. 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 an increase in resting heart rate of ≥10 beats / min or SBP / DBP ≥10 mm Hg is detected. Art., you must stop treatment. Patients with arterial hypertension who, on the background of antihypertensive therapy, have a blood pressure level above 145/90 mm Hg. Art., this control should be carried out especially carefully and, if necessary, at shorter intervals. Patients whose blood pressure twice, on repeated measurements, exceeded the level of 145/90 mm Hg. Art., treatment with Reduxin® should be canceled (see "Side Effects").

In patients with sleep apnea, blood pressure should be monitored especially carefully.

The simultaneous administration of drugs that increase the QT interval requires special attention. These drugs include histamine H1 receptor blockers (astemizole, terfenadine); antiarrhythmic drugs that increase the QT interval (amiodarone, quinidine, flecainide, mexiletine, propafenone, sotalol); stimulator of gastrointestinal motility cisapride; pimozide, sertindole, and tricyclic antidepressants. This also applies to conditions that can lead to an increase in the QT interval (hypokalemia and hypomagnesemia - see "Interaction").

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

Although there is no connection between taking the drug Reduxin® and the development of primary pulmonary hypertension, however, given the well-known risk for drugs in this group, with regular medical monitoring, special attention should be paid to symptoms such as progressive dyspnea (respiratory failure), chest pain and edema legs.

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