Reduxin Forte, 850 mg+15 mg 30 pcs

Pharmacotherapeutic group
Hypoglycemic agent of oral biguanide group. An agent for the treatment of obesity.

ATX code: A08A and A10BA02

Pharmacodynamics

Metformin
. An oral hypoglycemic drug of the biguanide group, reduces hyperglycemia without resulting in hypoglycemia. Unlike sulfonylurea derivatives, it does not stimulate insulin secretion and does not cause hypoglycemic effect in healthy people. Increases the sensitivity of peripheral receptors to insulin and glucose utilization by cells. Inhibits gluconeogenesis in the liver. Delays absorption of carbohydrates in the intestine and stimulates the production of GTP-1 (physiological regulator of appetite).

Metformin stimulates glycogen synthesis by acting on glycogen synthase. It increases transport capacity of all types of membrane glucose transporters. In addition, it has a favorable effect on lipid metabolism: it decreases concentrations of total cholesterol, low-density lipoproteins and triglycerides.

During metformin administration body weight remains stable or decreases moderately.

Sibutramine
It is a prodrug and shows its effect in vivo due to metabolites (primary and secondary amines) that inhibit monoamine reuptake (serotonin, noradrenaline and dopamine). The increase of neurotransmitters in synapses increases the activity of central 5NT-serotonin and adrenergic receptors and contributes to the physiological regulation of appetite by increasing the feeling of satiety and reducing the need for food, as well as increasing thermoproduction (internal energy expenditure). By activating β-adrenoceptors indirectly, sibutramine affects brown adipose tissue. Reduction of body weight when taking sibutramine is accompanied by an increase in serum concentration of high density lipoproteins (HDL) and a decrease in triglycerides, total cholesterol, low density lipoproteins (LDL) and uric acid.

Sibutramine and its metabolites do not affect the release of monoamines, do not inhibit monoamine oxidase (MAO); They have no affinity to a large number of neurotransmitter receptors, including serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2C), adrenergic (β1, β2, β3, α1, α2), dopamine (D1, D2), muscarinic, histamine (H1), benzodiazepine and glutamate NMDA receptors.

Simultaneous use of metformin and sibutramine increases the effectiveness of therapy in obese patients. By regulating appetite, reducing hunger, increasing energy expenditure and regulating lipid and carbohydrate metabolism, Reduxin® Forte reduces human body weight and restores metabolic health.

Clinical efficacy and safety (Results of clinical trials)
In a clinical trial in Reduxin® Forte group the percentage of patients who achieved clinically significant weight loss ≥5% over 3 months of therapy (early responders to therapy) exceeded 90%. During 6 months of therapy 91.67% of patients in the Reduxin® Forte group achieved a weight loss of 10% or more. The decrease of body weight was accompanied by clinically significant reduction of waist circumference and improvement of lipid profile, which proves the effectiveness of the drug in reducing the risk of complications and meets the main objectives of treatment of obesity.

No negative effect of Reduxin® Forte on the cardiovascular system parameters was observed during the study in patients with obesity.

Pharmacokinetics

absorption
After oral administration metformin is completely absorbed from the gastrointestinal tract. When concomitant intake of food, metformin absorption is reduced and delayed. Absolute bioavailability is 50-60%. Maximum plasma concentration (Cmax) is approximately 2 µg/ml or 15 µmol and is reached after 2.5 hours.

Distribution
Metformin is rapidly distributed in body tissues. Virtually not bound to plasma proteins.

Metabolism
Subject to little metabolism.

Elimation
It is excreted by the kidneys. Metformin clearance in healthy subjects is 400 ml/min (4 times higher than creatinine clearance (CK)), indicating active tubular secretion.

The half-life (T1/2) is approximately 6.5 h.

Pharmacokinetics in special clinical cases
In patients with renal insufficiency T1/2 is increased, there is a risk of metformin cumulation in the body.

Sibutramine

absorption
After oral administration is rapidly absorbed from the GI tract by at least 77 %. During “primary passage” through the liver, it undergoes biotransformation under the influence of CYP3A4 isoenzyme to form two active metabolites (monodesmethylsibutramine (M1) and didesmethylsibutramine (M2)). After a single dose of 15 mg, maximum blood concentration (Cmax) 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 reached in 1.2 h (sibutramine), 3-4 h (active metabolites). Simultaneous intake of food decreases Cmax of metabolites by 30% and increases the time to reach it by 3 h without changing the area under the curve “concentration-time” (AUC).

Distribution
Rapidly distributed in tissues. Protein binding is 97% (sibutramine) and 94% (M1 and M2). Equilibrium concentration of active metabolites in blood is reached within 4 days after the start of treatment and is approximately 2 times higher than the concentration in plasma after a single dose.

Metabolism and excretion
Active metabolites undergo hydroxylation and conjugation to form inactive metabolites, which are excreted mainly by the kidneys. The half-life of sibutramine is 1.1 h, M1 – 14 h, M2 – 16 h.

Pharmacokinetics in special clinical cases
The currently available data do not indicate the existence of clinically significant differences in pharmacokinetics in men and women.

Pharmacokinetics in the elderly
Pharmacokinetics in elderly healthy subjects (mean age 70 years) are similar to those in young adults.

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

Hepatic failure
Patients with moderate hepatic failure have a 24% higher AUC of active M1 and M2 metabolites after a single dose of sibutramine than in healthy subjects.

Indications

Active ingredient

Composition

Each 850 mg + 10 mg tablet contains:

Active ingredients:

metformin hydrochloride, 850.0 mg; sibutramine hydrochloride monohydrate, 10.0 mg;

Auxiliary substances:

Microcrystalline cellulose, croscarmellose sodium, povidone K-25, magnesium stearate;

Sheet film excipients:

Prepared coating system Opadray II 85F30656 blue (polyvinyl alcohol, macrogol, titanium dioxide, talc, brilliant blue dye with aluminum varnish, indigo carmine dye with aluminum varnish, iron oxide yellow dye).

Each tablet with a dosage of 850 mg + 15 mg containsit:

Active ingredients:

metformin hydrochloride, 850.0 mg; sibutramine hydrochloride monohydrate, 15.0 mg;

Auxiliary substances:

Microcrystalline cellulose, croscarmellose sodium, povidone K-25, magnesium stearate;

Sheet film excipients:

Prepared coating system Opadray II 85F48105 white (polyvinyl alcohol, macrogol, talc, titanium dioxide).

How to take, the dosage

Interaction

Special Instructions

Synopsis

Contraindications

Side effects

Overdose

Metformin

Symptoms: At a dose of 85 g of metformin (42.5 times the maximum daily dose) no hypoglycemia was observed, but the development of lactoacidosis was noted.

Significant overdose or associated risk factors can lead to the development of lactoacidosis.

Treatment: In case of signs of lactocidosis the drug treatment should be stopped immediately, the patient should be urgently hospitalized and, after determining the lactate concentration, the diagnosis should be confirmed. The most effective measure for elimination of lactate and metformin from the body is hemodialysis. Asymptomatic treatment is also carried out.

Sibutramine

There are extremely limited data on sibutramine overdose. The most common adverse reactions associated with overdose are: tachycardia, increased blood pressure, headache, dizziness. It is necessary to inform your attending physician in case of suspected overdose.

Treatment: there is no specific treatment or antidotes. It is necessary to perform general measures: to ensure free breathing, to monitor the state of the cardiovascular system, as well as, if necessary, to carry out supportive symptomatic therapy. Timely use of activated charcoal, as well as gastric lavage can reduce sibutramine intake into the body. Patients with high blood pressure and tachycardia may be prescribed β-adrenoblockers. The effectiveness of forced diuresis or hemodialysis has not been established. In case of overdose, the drug Reduxin® Forte should be stopped immediately.

Pregnancy use