REDUXIN MET CAPSULE SET 15 MG + 153.5 MG №30 AND PILLS 850 MG

pharmachologic effect

Reduxin® Meth contains two separate drugs in the same package: a hypoglycemic agent for oral administration of the biguanide group in the pill dosage form - Metformin, and an agent for treating obesity in the capsule dosage form, containing sibutramine and microcrystalline cellulose.

Metformin

Oral hypoglycemic drug from the group of biguanides. reduces hyperglycemia without leading to the development of hypoglycemia. Unlike sulfonylureas, it does not stimulate insulin secretion and does not cause a hypoglycemic effect in healthy individuals. Increases the sensitivity of peripheral receptors to insulin and glucose utilization by cells. Inhibits gluconeogenesis in the liver. Delays the absorption of carbohydrates in the intestines. Metformin stimulates glycogen synthesis by acting on glycogen synthase. Increases the transport capacity of all types of membrane glucose transporters. In addition, it has a beneficial effect on lipid metabolism: it lowers total cholesterol, LDL and triglycerides.

While taking metformin, the patient's body weight either remains stable or decreases moderately.

Sibutramine

It is a prodrug and exerts its action in vivo due to 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 serotonin 5HT receptors and adrenoreceptors, which increases the sense of fullness and reduces the need for food, as well as an increase in thermal production. Indirectly activating β3-adrenoreceptors, sibutramine affects brown adipose tissue. A decrease in body weight is accompanied by an increase in the serum HDL concentration 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; do not have affinity for a large number of neurotransmitter receptors, including serotonin receptors (5-HT1, 5-HT1A, 5-HT1B, 5-NT2C), adrenoreceptors (β1, β2, β3, α1, α2), dopamine (D1, D2), muscarinic, histamine (H1), benzodiazepine and glutamate NMDA receptors.

Microcrystalline cellulose

It is an enterosorbent, has sorption properties and non-specific detoxification action. It binds and removes from the body various microorganisms, their metabolic products, exogenous and endogenous toxins, allergens, xenobiotics, as well as an excess of certain metabolic products and metabolites responsible for the development of endogenous toxicosis.

Simultaneous use metformin and sibutramine with microcrystalline cellulose increases the therapeutic efficacy of the combination used in patients with overweight and type 2 diabetes.

Pharmacokinetics

Metformin

Suction

After taking the drug inside Metformin completely absorbed from the gastrointestinal tract. With simultaneous ingestion, the absorption of metformin is reduced and delayed. Absolute bioavailability is 50-60%. Cmax in plasma it is approximately 2 μg / ml or 15 μmol and is reached after 2.5 h.

Distribution

Metformin is rapidly distributed in body tissues. Practically does not bind to plasma proteins.

Metabolism

To a very small extent is metabolized.

Removal

Excreted by the kidneys. The clearance of metformin in healthy individuals is 400 ml / min (4 times more than CC), which indicates an active tubular secretion.

T1/2 is approximately 6.5 h.

Pharmacokinetics in Special Patient Groups

In patients with renal insufficiency T1/2 increases, there is a risk of cumulation of metformin in the body.

Sibutramine

Suction

After ingestion is rapidly absorbed from the gastrointestinal tract by at least 77%. During the "first pass" through the liver, it undergoes biotransformation under the influence of CYP3A4 isoenzyme with the formation of two active metabolites (monodesmethylsibutramine (M1) and diddesmethylsibutramine (M2)). After taking a single dose of 15 mg Cmax in the blood of monodesmethylsibutramine (M1) is 4 ng / ml (3.2-4.8 ng / ml), didesmethylsibutramine (M2) - 6.4 ng / ml (5.6-7.2 ng / ml). Cmax is achieved after 1.2 h (sibutramine), 3-4 h (active metabolites). Simultaneous food intake lowers Cmax metabolites by 30% and increases the time it reaches 3 hours, without changing the AUC.

Distribution

It is quickly distributed on fabrics. Protein binding is 97% (sibutramine) and 94% (M1 and M2). Css active metabolites in the blood is achieved within 4 days after the start of treatment and about 2 times higher than the concentration in the blood plasma after taking a single dose.

Metabolism and excretion

Active metabolites undergo hydroxylation and conjugation to form inactive metabolites, which are excreted primarily by the kidneys. T1/2 sibutramine - 1.1 h, M1 - 14 h, M2 -16 h.

Pharmacokinetics in special clinical situations

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

Pharmacokinetics elderly healthy individuals (average age 70 years) similar to that of the young.

Renal failure does not affect the AUC of the active metabolites M1 and M2, except for the metabolite M2 in patients with end-stage renal disease who are on dialysis.

Patients with moderate liver failure after a single dose of sibutramine AUC active metabolites M1 and M2 are 24% higher than in healthy individuals.

Indications

- for weight loss with alimentary obesity with a body mass index of 27 kg / m2 and more in combination with type 2 diabetes and dyslipidemia.

Dosing regimen

The drug is taken orally. pills and capsules should be taken in the morning at the same time, without chewing and washing down with a sufficient amount of liquid (1 glass of water) in combination with food intake.

The recommended starting dose is 1 pill containing 850 mg of metformin and 1 capsule containing 10 mg of sibutramine.

You should follow the dynamics of changes in the concentration of glucose in the blood and the dynamics of weight loss. If after 1-2 weeks the optimal values ​​of glucose concentration in the blood are not reached, the dose of metformin should be increased to 2 tab.

The usual maintenance dose of metformin is 1700 mg / day. The maximum daily dose of metformin is 2550 mg. To reduce side effects from the gastrointestinal tract, the daily dose of metformin can be divided into 2 doses. For example, take 1 tab. in the morning and 1 tab. in the evening.

If, within 4 weeks from the start of treatment, a decrease in body weight of 2 kg is not achieved, the dose of sibutramine is increased to 15 mg / day. Reduxin Treatment® Meth should not last more than 3 months in patients who do not respond well to therapy, i.e. who within 3 months of treatment can not achieve weight loss by 5% of the original indicator. Treatment should not be continued if, with further therapy after the achieved weight loss, the patient again gains 3 kg or more in body weight.

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

Reduxin Treatment® Met should be carried out in conjunction with diet and exercise under the supervision of a physician with practical experience in treating obesity.

Side effect

Determination of the frequency of side effects: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10 000, <1 / 1000), very rarely (<1/10 000). Side effects are presented in order of decreasing significance.

Metformin

Metabolism: very rarely - lactic acidosis; long-term use may reduce the absorption of vitamin B12. Decreased Vitamin B Concentration12 must be taken into account in patients with megaloblastic anemia.

From the nervous system: often - a violation of taste.

From the digestive system: very often - nausea, vomiting, diarrhea, abdominal pain, lack of appetite (most often these symptoms occur in the initial period of treatment and in most cases pass spontaneously); very rarely - a violation of liver function indicators, hepatitis (after the cancellation of metformin, these undesirable effects completely disappear). Slow increase in dose may improve gastrointestinal tolerance.

From the skin: very rarely - skin reactions such as erythema, pruritus, rash.

Sibutramine

Most often, side effects occur at the beginning of treatment (in the first 4 weeks). Their severity and frequency weaken over time. Side effects are, in general, not heavy and reversible. Side effects, depending on the effects on organs and organ systems, are presented in the following order: very often (≥1 / 10), often (≥1 / 100, <1/10).

From the nervous system: very often - dry mouth and insomnia; often - headache, dizziness, anxiety, paresthesias, as well as a change in taste.

Since the cardiovascular system: often - tachycardia, palpitations, increased blood pressure, vasodilation. There is a moderate rise in blood pressure at rest at 1-3 mm Hg. and a moderate increase in heart rate of 3-7 beats / min. In some cases, a more pronounced increase in blood pressure and an increase in 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).

From the digestive system: very often - loss of appetite, constipation; often - nausea, exacerbation of hemorrhoids. With a tendency to constipation in the first days is necessary to control the evacuation function of the intestine. When constipation occurs, the drug is stopped and a laxative is taken.

From the skin: often - increased sweating.

In isolated cases When treating sibutramine, the following undesirable clinically significant events are described: dysmenorrhea, edema, flu-like syndrome, skin itching, back pain, abdominal pain, paradoxical increase in appetite, thirst, rhinitis, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, acute interstitial nephritis, bleeding, Schönlein-Genoch purpura (hemorrhages in the skin), convulsions, thrombocytopenia, transient increase in liver enzymes in the blood.

Use of the drug Reduxin® Met in patients with elevated blood pressure - see sections "Contraindications" and "Special Instructions".

In progress postmarketing research Sibutramine has been described for additional adverse reactions listed below for organ systems.

Since the cardiovascular system: atrial fibrillation.

Allergic reactions: hypersensitivity reactions (from mild skin rash and urticaria to angioedema (angioedema) and anaphylaxis).

From the side of the central nervous system: psychosis, states of suicidally directed thinking, suicide and mania, short-term memory impairment, convulsions. In the event of such conditions, the drug must be canceled.

From the senses: blurred vision ("the veil before eyes").

From the digestive system: diarrhea, vomiting.

From the skin: alopecia.

From the urinary system: urine retention.

From the reproductive system: Ejaculation / orgasm disorders, impotence, menstrual disorders, uterine bleeding.

Contraindications

- hypersensitivity to the drug;

- diabetic ketoacidosis, diabetic precoma, diabetic coma;

- impaired renal function (CC less than 45 ml / min);

- abnormal liver function;

- Acute conditions in which there is a risk of developing impaired renal function: dehydration (with diarrhea, vomiting), serious infectious diseases, shock;

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

- uncontrolled arterial hypertension (blood pressure above 145/90 mm Hg);

- clinical manifestations of acute and chronic diseases that can lead to the development of tissue hypoxia (including respiratory failure, acute heart failure, chronic heart failure with unstable hemodynamic parameters, acute MI);

- chronic alcoholism, acute ethanol poisoning;

- thyrotoxicosis;

- benign prostatic hyperplasia;

- pheochromocytoma;

- angle-closure glaucoma;

- extensive surgeries and injuries (when insulin therapy is indicated);