REDUKSIN®

Active material: microcrystalline cellulose, Siʙutramin
When ATH: A08AA10
CCF: Anti-obesity medication centrally acting
ICD-10 codes (testimony): E66
When CSF: 16.02.01
Manufacturer: AMK-Pharm Ltd. (Russia)

Pharmaceutical form, composition and packaging

Capsules №2 blue; contents of capsules – powder white or white with a slightly yellowish tint.

Excipients: calcium stearate.

Ingredients of the capsule shell: colorant titanium dioxide, dye azorubin, patent blue dye, gelatin.

10 PC. – packings Valium planimetric (aluminum / PVC) (3) – packs cardboard.
10 PC. – packings Valium planimetric (aluminum / PVC) (6) – packs cardboard.

Capsules №2 blue; contents of capsules – powder white or white with a slightly yellowish tint.

Excipients: calcium stearate.

Ingredients of the capsule shell: colorant titanium dioxide, patent blue dye, gelatin.

10 PC. – packings Valium planimetric (aluminum / PVC) (3) – packs cardboard.
10 PC. – packings Valium planimetric (aluminum / PVC) (6) – packs cardboard.

Pharmacological action

Combination drug to treat obesity, action is due to its constituent components. Sibutramine is a prodrug and exerts its effect in vivo due to metabolites (primary and secondary amines), inhibiting the reuptake of monoamines (primarily serotonin and norepinephrine). The increase of neurotransmitters in the synapses increases the activity of central serotonin 5-HT-receptors and adrenoceptors, which increases satiety and reduce the need for food, as well as an increase in termoproduktsii. Опосредованно активируя b₃-adrenoreceptory, Sibutramine acts on brown adipose tissue. Weight loss accompanied by an increase in the serum concentration of HDL and decreased triglyceride, total cholesterol, LDL, Uric acid.

Sibutramine and its metabolites do not affect the release of monoamines, not inhibit MAO; It has no affinity to a large number of neurotransmitter receptors, including serotonin (5-HT₁, 5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2C), adrenoreceptory (b₁, b₂, b₃, a₁, a₂), dopamine (D₁, D₂), muscarinic, histamine (H₁), benzodiazepine and NMDA-receptors.

Microcrystalline cellulose is enterosorbent, It has sorption properties and non-specific detoxication effect. Bind and remove various microorganisms from the body, their metabolic products, toxins exogenous and endogenous nature, allergens, xenobiotic, and excess of certain metabolic products and metabolites, responsible for the development of endogenous toxemia.

Pharmacokinetics

Absorption, distribution, metabolism

After oral administration of sibutramine is rapidly absorbed from the gastrointestinal tract, at least 77%. Treated effect “first pass” biotransformed in the liver and involving isoenzyme CYPZA4 to form two active metabolites (mono- and didesmetilsibut-ramin). After receiving a single dose of 15 mg C_max monodesmetilsibutramina is 4 ng / ml (3.2-4.8 ng / ml), didesmetilsibutramina – 6.4 ng / ml (5.6-7.2 ng / ml). C_max sibutramine achieved through 1.2 no, active metabolite – through 3-4 no. Receiving simultaneously with food reduces the C_max metabolites 30% and increases the time to achieve it 3 no, without changing the AUC. It is rapidly distributed to the tissues. The binding of sibutramine to plasma proteins is 97%, and mono- and didesmetilsibutramina – 94%. C_ss active metabolites in blood reached within 4 days after treatment initiation, and approximately 2 times the plasma levels after administration of a single dose of.

Deduction

T_1/2 siʙutramina – 1.1 no, monodesmetilsibutramina – 14 no, didesmetilsibutramina – 16 no. Active metabolites are hydroxylation and conjugation with formation of inactive metabolites, which are derived mainly kidneys.

Testimony

To reduce the body weight at the following conditions:

- Alimentary obesity with a body mass index (BMI) 30 kg / m² and more;

- Alimentary obesity with a BMI 27 kg / m² or more in combination with other risk factors, due to overweight (diabetes mellitus type 2 /non-insulin / or dyslipoproteinemia).

Dosage regimen

Reduksin^® appointed interior 1 time / day. Dose set individually, depending on tolerability and clinical efficacy. The recommended starting dose – 10 mg, bad Portability can receive a dose of 5 mg. The capsules should be taken in the morning, not chewing and drinking plenty of fluids. The drug can be taken on an empty stomach, and combine with a meal.

If during the 4 weeks of treatment is not achieved a reduction in body weight 5% and more, then increase the dose to 15 mg / day. Duration of therapy Reduxine^® should not exceed 3 months for patients, are not well respond to therapy (ie. that during 3 months of treatment fails to reduce the weight 5% of initial body weight). Treatment should not continue, if further treatment (after achieved weight loss) the patient is re-gaining body weight 3 kg or more.

The total duration of therapy should not exceed 2 year, as for a more prolonged period of sibutramine data on efficacy and safety absent.

Therapy Reduxine^® must be treated by a doctor, have practical experience in the treatment of obesity. The drug should be combined with diet and exercise.

Side effect

Side effects, depending on the effects on organs and organ systems, are presented in the following order (often – >10%, sometimes – 1-10%, rarely – < 1%).

From the central and peripheral nervous system: often – dry mouth, insomnia; sometimes – headache, dizziness, anxiety, paresthesia, as well as changes in taste; in a few cases – backache, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, convulsions.

One patient with schizoaffective violation, which presumably existed prior to treatment, after treatment developed acute psychosis.

Cardio-vascular system: sometimes – tachycardia, heartbeat, increased blood pressure, vasodilation. There has been a moderate rise in blood pressure at rest on 1-3 mmHg. and a moderate increase in pulse on 3-7 bpm. In some cases, are not excluded more severe increase in blood pressure and heart rate. Clinically significant changes in blood pressure and heart rate are recorded mainly in the beginning of treatment (first 4-8 weeks).

From the digestive system: often – loss of appetite, constipation; sometimes – nausea, aggravation of hemorrhoids. When a tendency to constipation in the first days necessary to monitor the evacuation function of the intestine. If you experience constipation receiving end and take a laxative. In rare cases, pain in the abdomen, paradoxical increased appetite, transient increase in liver enzymes.

Dermatological reactions: sometimes – Sweating; in a few cases – itching, purpura Shenleyn-Genoa (bleeding into the skin).

From the body as a whole: in a few cases described in the following clinically significant adverse effects: dysmenorrhoea, swelling, flu-like symptoms, thirst, rhinitis, acute interstitial nephritis, bleeding, thrombocytopenia.

Reactions to cancel, such as headache or increased appetite, are rare. There is no evidence, observed that after treatment withdrawal syndrome, withdrawal or mood disorders.

The most common side effects occur early in treatment (first 4 of the week). Their severity and frequency over time weaken. Side effects are, generally, and lightweight and reversible.

Contraindications

- Availability of organic causes of obesity (eg, gipotireoz);

- Serious eating disorders (anorexia nervosa or bulimia nervosa);

- Mental illness;

- Syndrome of Gilles de la Tourette (generalized tics);

- Simultaneous MAO inhibitors (eg, phentermine, fenfluramina, dexfenfluramine, ethylamphetamine, ephedrine) or their use for 2 weeks before prescribing Reduxine^®; the use of other drugs, acting on the central nervous system (eg, Antidepressants, neuroleptics); preparations, prescribed for sleep disorders, containing tryptophan, and other central acting drugs for weight loss;

- CHD, decompensated chronic heart failure, congenital heart disease, occlusive peripheral arterial disease, tachycardia, Arrhythmia, cerebrovascular diseases (stroke, transient ischemic attacks);

- Uncontrolled hypertension (BP above 145/90 mmHg.);

- Thyrotoxicosis;

- Severe liver;

- Severe renal dysfunction;

- Benign prostatic hyperplasia;

- Pheochromocytoma;

- Zakrыtougolynaya glaucoma;

- Established drug, drug or alcohol dependence;

- Pregnancy;

- Lactation (breast-feeding);

- Childhood and adolescence up 18 years;

- Old age older 65 years;

- Established hypersensitivity to sibutramine or to other components of the drug.

FROM caution should be prescribed in the following states: arrhythmia history, chronic circulatory insufficiency, coronary artery disease (incl. history), cholelithiasis, arterial hypertension (controlled and history), neurological disorders, including mental retardation and seizures (incl. history), liver dysfunction and / or kidney disease and mild to moderate severity, motor and verbal tics history.

Pregnancy and lactation

The drug should not be used during pregnancy due to lack of sufficient number of studies on the safety of sibutramine impact on the fetus.

Women of childbearing age while receiving Reduxine^® You should use contraceptives.

Reduksin^® should not be used during breastfeeding.

Cautions

Reduksin^® It should be applied only in cases, when all non-pharmacological interventions to reduce body weight are ineffective – if the reduction of body weight for 3 months was less than 5 kg.

Treatment Reduxine^® It must be carried out within the framework of complex therapy for weight loss under medical supervision, have practical experience in the treatment of obesity.

Combined therapy of obesity involves changes in both diet and lifestyle, and increased physical activity. An important component of therapy is to create the prerequisites to permanent change in eating habits and lifestyle, needed to maintain the achieved weight loss after discontinuation of drug therapy. Patients should be under the therapy with Reduxine^® to change your lifestyle and habits so, after completion of treatment to ensure preservation of the achieved weight loss. Patients need to be clear about, that non-compliance will lead to re-weight gain and repeated appeals to the doctor.

Patients, taking Reduxine^®, necessary to measure blood pressure and heart rate. First 2 months of treatment, these parameters should be monitored every 2 of the week, and then monthly. In patients with hypertension (which on the background of antihypertensive therapy blood pressure above 145/90 mmHg.) This monitoring should be carried out carefully and, if necessary, at shorter intervals. Patients, whose blood pressure twice with repeated measurements exceed the level 145/90 mm.rt. Article. treatment with Reduxine^® to be suspended .

Special attention should be given co-administration of drugs, increase the QT interval. These medications include histamine H₁-receptors (astemizol, terfenadine); antiarrhythmic drugs, prolonging the QT interval (Amiodarone, quinidine, flekainid, mexiletine, propafenone, sotalol); GI motility stimulants (cisapride, pimozid, sertindole and tricyclic antidepressants). Caution should be observed when using the drug on a background of states, which are risk factors in increasing QT interval (kaliopenia, gipomagniemiya).

The interval between the reception of MAO inhibitors and Reduxine^® must be at least 2 weeks.

The relationship between the reception Reduxine^® and the development of primary pulmonary hypertension is not installed , However, given the well-known risk of drugs of this group, with regular medical monitoring is necessary to pay special attention to symptoms, as a progressive dyspnea (respiratory failure), chest pain and swelling in the legs.

Effects on ability to drive vehicles and management mechanisms

The drug Reduxine^® may limit the patient's ability to drive vehicles and management mechanisms.

Overdose

There are very limited data about overdose sibutramine.

Symptoms: increased severity of side effects. Specific signs of an overdose are not known.

Treatment: administration of activated charcoal, gastric lavage, simptomaticheskaya therapy, with an increase in blood pressure and tachycardia – appointment of beta-blockers. No specific antidote. It is necessary to perform common actions: provide free breath, monitor the state of the cardiovascular system, and if necessary to carry out maintenance symptomatic therapy. The effectiveness of forced diuresis or hemodialysis is not installed.

Drug Interactions

Inhibitors of microsomal oxidation, incl. CYP3A4 inhibitors (incl. ketoconazole, Erythromycin, cyclosporine) increase in plasma concentrations of metabolites of sibutramine with an increase in heart rate and clinically insignificant increase in the QT interval. Rifampicin, macrolide antibiotics, phenytoin, Carbamazepine, phenobarbital and dexamethasone may accelerate the metabolism of sibutramine. The simultaneous use of several drugs, increasing the concentration of serotonin in the blood, It can lead to serious interactions. The so-called serotonin syndrome may develop in rare cases while applying Reduxine^® with selective serotonin reuptake inhibitors (drugs for the treatment of depression), some drugs for treating migraine (sumatriptan, digidroergotamin), with potent analgesics (pentazocin, pethidine, Fentanyl) or antitussive drugs (dextromethorphan). Sibutramine has no effect on the effect of oral contraceptives.

At the same time taking sibutramine and ethanol there were no gain negative effect of ethanol. However, alcohol is absolutely not compatible with the recommended dietary while taking sibutramine activities.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in a dry, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 3 year.