Reduxin Forte tabs #30

Instruction for Reduxin Forte

Reduxin Forte - a drug for the treatment of obesity from the biguanide group.

Release form and composition

Reduxin Forte is available in the form of film-coated tablets:
    tablets with a dosage of 850 mg + 10 mg: biconvex, oval, coated with a blue film membrane, with a dividing line on one side, white at a break;
    tablets with a dosage of 850 mg + 15 mg: biconvex, oval, coated with a white film membrane, with a dividing line on one side, white at a break.
Tablets, regardless of dosage, are packaged in blisters of 5, 7, 10 or 15 pcs. or in cans of polyethylene terephthalate 10, 15, 30, 60, 75, 100, 120 or 180 pcs. In a cardboard bundle from 1 to 10 blisters or 1 can and instructions for use Reduxin Forte.
Composition per 1 tablet, film-coated:
    active substances: metformin (in the form of metformin hydrochloride) - 850 mg, sibutramine (in the form of sibutramine hydrochloride monohydrate) - 10 mg or 15 mg;
    auxiliary components of the tablet core: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone K-25;
    film coating: for Reduxin Forte tablets 850 mg + 10 mg - Opadry II 85F30656 blue (titanium dioxide, polyvinyl alcohol, indigo carmine dye with aluminum varnish, macrogol, yellow iron oxide dye, diamond blue dye with aluminum varnish, talc); for Reduxin Forte tablets 850 mg + 15 mg - Opadray II 85F48105 white (talc, polyvinyl alcohol, titanium dioxide, macrogol).

Pharmacodynamics

Reduxin Forte contains two active components - metformin and sibutramine.
Metformin is an oral hypoglycemic agent from the biguanide group. It reduces hyperglycemia, but does not lead to hypoglycemia. It differs from sulfonylurea derivatives in that it does not stimulate insulin secretion, and also does not cause hypoglycemic effects in healthy individuals.
Under the influence of metformin, the sensitivity of peripheral receptors to insulin increases and glucose utilization by cells increases. It slows down gluconeogenesis in the liver, inhibits intestinal absorption of carbohydrates. By acting on glycogen synthase, metformin stimulates the synthesis of glycogen. In addition, it increases the transport capacity of all types of glucose membrane transporters.
Metformin favorably affects lipid metabolism: it reduces the content of LDL (low density lipoproteins), triglycerides and total cholesterol.
Reception of metformin leads to a moderate decrease in body weight or allows you to stabilize weight.
Sibutramine is a prodrug from which, as a result of metabolism, active primary and secondary amines are formed that inhibit the reuptake of dopamine, norepinephrine and serotonin. Due to an increase in the concentration of neurotransmitters in synapses, the activity of central adrenergic and 5HT-serotonin receptors increases, and this leads to a decrease in food demand, an increase in heat generation and a feeling of satiety.
Due to the indirect activation of β3-adrenergic receptors, sibutramine affects brown adipose tissue. With a decrease in body weight while taking sibutramine in blood serum, the concentration of HDL (high density lipoproteins) increases and the level of total cholesterol, triglycerides, uric acid and LDL decreases.
The metabolites of sibutramine and sibutramine itself do not inhibit MAO (monoamine oxidase) and do not affect the release of monoamines; they do not have an affinity for most neurotransmitter receptors, including muscarinic, benzodiazepine, serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2C), histamine (H1), dopamine (D1, D2), glutamate NMDA -receptors and adrenergic (β1 β2, β3, α1, α2) receptors.

Pharmacokinetics

After taking Reduxin Forte, metformin is almost completely absorbed in the digestive tract. Simultaneous eating reduces and slows down its absorption. Absolute bioavailability is 50-60%. In blood plasma, the maximum concentration is reached after 2.5 hours and is approximately 15 μmol or 2 μg / ml. Metformin almost does not bind to plasma proteins. It is rapidly distributed in tissues and organs.
It is metabolized to a small extent. Excretion is carried out by the kidneys. In healthy people, metformin clearance is 400 ml / min (this is 4 times higher than creatinine clearance, which indicates active secretion in the tubules of the kidneys). The elimination half-life is about 6.5 hours. With renal failure, the elimination half-life is lengthened (the risk of cumulation of the active substance increases).
Sibutramine is absorbed from the digestive tract by at least 77%. Suction is quick. It undergoes the effect of the primary passage through the liver (biotransformed under the influence of the isoenzyme CYP3A4). As a result of biotransformation, two active metabolites are formed - M1 (monodesmethylsibutramine) and M2 (didesmethylsibutramine). After ingestion of a single dose in an amount of 15 mg, the maximum plasma concentration of M1 is 3.2–4.8 ng / ml (average 4 ng / ml), and M2 - 5.6–7.2 ng / ml (average 6 4 ng / ml). The maximum concentration of sibutramine in plasma is reached after 1.2 hours, and its active metabolites after 3-4 hours. Eating reduces the maximum level of metabolites in plasma by 30% and lengthens its time to reach almost 3 hours, while the area under the pharmacokinetic the curve "concentration - time" (AUC), does not change. Sibutramine is rapidly distributed in organs and tissues, its connection with plasma proteins is 97%. Metabolites M1 and M2 bind to plasma proteins by 94%. The equilibrium concentration of metabolites in plasma is reached within 4 days after the start of therapy. It is almost 2 times higher than plasma concentration after taking a single dose of the drug.
The active metabolites of sibutramine are hydroxylated and conjugated. Inactive metabolites resulting from these processes are mainly excreted by the kidneys. The half-life of sibutramine is 1.1 hours, metabolite M1 - 14 hours, and M2 - 16 hours.
In men and women, the pharmacokinetics of sibutramine is not significantly different. In elderly healthy people, the pharmacokinetics corresponds to those in young people.
In renal failure, the AUC of M1 and M2 remains almost unchanged. In patients with end-stage renal failure who are on dialysis, the AUC of M2 metabolite is different.
With moderate liver failure, the AUC of active metabolites after a single dose of sibutramine is 24% higher than in healthy people.

Indications for use

Reduxin Forte is used to reduce body weight in the following cases:
    Alimentary obesity in patients with a BMI (body mass index) ≥ 27 kg / m2 in combination with dyslipidemia and type 2 diabetes mellitus;
    Alimentary obesity in patients with a BMI> 30 m2 with prediabetes and the presence of one or more risk factors for the development of type 2 diabetes mellitus (if adequate glycemic control is not achieved with a change in lifestyle).

Contraindications

Absolute:
    impaired liver function;
    impaired renal function (with creatinine clearance less than 45 ml / min);
    diseases of the cardiovascular system at present or in the anamnesis (chronic heart failure in the stage of decompensation, arrhythmia, tachycardia, coronary heart disease, transient disturbances of cerebral circulation, occlusive lesions of the peripheral arteries);
    uncontrolled arterial hypertension (with arterial pressure above 145/90 mm Hg).
    diabetic precoma and coma, diabetic ketoacidosis;
    chronic and acute diseases with clinically expressed symptoms that are potentially capable of causing tissue hypoxia (including acute myocardial infarction, respiratory and heart failure);
    acute conditions accompanied by a risk of developing renal dysfunction (for example, severe infectious diseases, vomiting, diarrhea, shock);
    thyrotoxicosis;
    pheochromocytoma;
    increased concentration of lactic acid in the blood (lactic acidosis), including a history of;
    benign prostatic hyperplasia;
    angle-closure form of glaucoma;
    mental illness;
    serious eating disorders (eg, bulimia nervosa or anorexia);
    the presence of organic causes of obesity (for example, obesity due to hypothyroidism);
    acute ethanol poisoning, chronic alcoholism;
    generalized tics (Tourette syndrome);
    children and adolescents under 18 years of age;
    old age over 65 years old;
    During pregnancy and breastfeeding;
    adherence to a low-calorie diet (less than 1000 kcal per day);
    established drug or pharmacological dependence;
    injuries or extensive surgical interventions (when there are indications for insulin therapy);
    co-administration with sleeping pills containing tryptophan and other centrally acting drugs designed to treat mental disorders or reduce body weight;
    simultaneous administration of serotonin reuptake inhibitors (antipsychotics, antidepressants, etc.);
    simultaneous administration of MAO inhibitors or their use 2 weeks before or 2 weeks after taking sibutramine;
    X-ray or radioisotope studies with the introduction of an iodine-containing contrast medium (48 hours before and 48 hours after this study);
    hypersensitivity to the main or auxiliary components of the tablets.
Relative (Reduxin Forte tablets are used with caution):
    impaired renal function (creatinine clearance from 45 to 59 ml / min);
    cholelithiasis;
    chronic circulatory failure;
    history of cardiac arrhythmias;
    coronary artery disease (except for angina pectoris and myocardial infarction), including a history of;
    controlled arterial hypertension, including a history of;
    bleeding disorders, bleeding tendency;
    history of verbal and motor tics;
    epilepsy;
    neurological disorders, including convulsions and mental retardation (including a history);
    glaucoma (except for the angle-closure form of glaucoma);
    elderly age from 60 to 65 years (especially when patients perform heavy physical work, which increases the risk of lactic acidosis);
    simultaneous administration of drugs that affect platelet function or hemostasis.

Reduxin Forte, instructions for use: method and dosage

Reduxin Forte tablets are taken orally, once a day.
The dose of the drug is selected individually (taking into account the tolerance of the drug and its clinical effectiveness).
At the beginning of treatment, Reduxin Forte is prescribed 850 mg + 10 mg once a day.
Tablets should be taken in the morning, swallowed whole and washed down with at least one glass of water or other liquid (on an empty stomach or in combination with food). After 4 weeks of taking the drug, the achieved decrease in body weight is estimated. If this indicator is less than 5%, then the patient is transferred to Reduxin Forte 850 mg + 15 mg once a day.
In patients who do not respond well to therapy (if body weight has decreased by less than 5% of the initial level during 3 months of treatment), Reduxin Forte can be used for no more than 3 months. The therapy should not be continued even if, after the achieved decrease in body weight during further treatment, it again increases by 3 kg or more.
The total duration of the course is no more than 1 year, since there is no data on the safety and effectiveness of sibutramine with prolonged use.
Reduxin Forte treatment must be combined with exercise and diet, as well as under the supervision of a physician who has practical experience in treating obesity. After completing the course of treatment with the drug, it is recommended to transfer the patient to metformin monotherapy.

Side effects

Side effects of Reduxin Forte due to metformin:
    digestive system: very often - vomiting, nausea, lack of appetite, abdominal pain, diarrhea (these symptoms usually occur at the beginning of treatment and, as a rule, pass spontaneously);
    hepatobiliary system: very rarely - hepatitis and impaired liver function (disappear completely after discontinuation of the drug);
    metabolism and nutrition: very rarely - an increase in the concentration of lactic acid in the blood; with prolonged therapy - a decrease in the absorption of vitamin B12 (should be taken into account when prescribing Reduxin Forte to patients with megaloblastic anemia);
    nervous system: often - taste disturbance;
    skin and subcutaneous fat: very rarely - a rash on the skin, itching, erythema and other skin reactions.
Undesirable side effects due to sibutramine:
    digestive system: very often - constipation, loss of appetite; often - exacerbation of hemorrhoids, nausea (in patients with a tendency to constipation in the early days, it is necessary to control the evacuation function of the intestine, and in case of constipation - cancel Reduxin Forte and prescribe a laxative);
    cardiovascular system: often - palpitations, tachycardia; the frequency is unknown - vasodilation, a moderate increase in blood pressure (by 1-3 mm Hg. Art. at rest), a moderate increase in heart rate (by 3–7 beats per minute);
    nervous system: very often - a feeling of dryness in the oral cavity, insomnia; often - taste change, dizziness, paresthesia, headache, anxiety;
    skin and subcutaneous fat: often - increased sweating;
    other reactions: isolated cases - flu-like syndrome, thirst, paradoxical increase in appetite, rhinitis, swelling, bleeding, skin hemorrhage, acute interstitial nephritis, skin itching, dysmenorrhea, abdominal and back pain, transient increase in liver enzyme activity, thrombocytopenia, anxiety, drowsiness, irritability, convulsions, depression, emotional lability.
Additional side effects of sibutramine identified during post-marketing use of Reduxin Forte:
    digestive system: vomiting, diarrhea;
    cardiovascular system: atrial fibrillation;
    nervous system and sensory organs: blurred vision (feeling veiled in front of the eyes), short-term visual disturbances, convulsions;
    mental disorders: mania, suicidal thinking, psychosis, suicide (in case of such conditions, treatment with the drug should be canceled);
    urinary system: urinary retention;
    skin and subcutaneous fat: pathological hair loss;
    genitals and mammary gland: uterine bleeding, menstrual irregularities, erectile dysfunction, orgasm / ejaculation disorders;
    immune system: urticaria, skin rashes, Quincke's edema, anaphylactic reactions.

Overdose

When metformin was used in a daily dose of 85 g (exceeding the maximum daily dose by 42.5 times), there were no symptoms of hypoglycemia, however, cases of the development of lactic acidosis were noted.
If signs of lactic acidosis appear, therapy should be discontinued, and the patient urgently hospitalized (to clarify the diagnosis, it is necessary to determine the content of lactate in the blood). The most effective way to remove metformin and lactate from the body is hemodialysis. Symptomatic therapy is also performed.
Data on an overdose of sibutramine is extremely limited. Most often, the following reactions associated with its overdose are found: dizziness, headache, increased blood pressure, tachycardia. In case of suspected intoxication, Reduxin Forte should be immediately withdrawn and the doctor advised.
There is no specific antidote for sibutramine. Also there is no special treatment. Therapy is symptomatic and supportive. The patient should be given activated charcoal in a timely manner and rinse the stomach. It is necessary to ensure free breathing and monitor the state of the cardiovascular system. With tachycardia and high blood pressure, β-blockers are prescribed. The effectiveness of hemodialysis or forced diuresis for the excretion of sibutramine has not been established.

Special instructions

Lactic acidosis

Lactic acidosis is a rare but serious complication that, if timely treatment is not given, can lead to death. In patients with diabetes mellitus and severe renal failure, the likelihood of lactic acidosis while taking Metformin is higher than in other groups.
The incidence of lactic acidosis can be reduced if you take into account some other associated risk factors, for example, prolonged fasting, liver failure, ketosis, alcoholism, decompensated diabetes mellitus and any conditions associated with severe hypoxia.
Sometimes the development of lactic acidosis is preceded by the appearance of nonspecific symptoms, such as muscle cramps, which are accompanied by abdominal pain, dyspeptic disorders and severe asthenia. With lactic acidosis, the patient experiences abdominal pain, shortness of breath, hypothermia, and subsequent coma.
The diagnosis of lactic acidosis is confirmed by laboratory tests: the plasma lactate concentration exceeds 5 mmol / l, the blood pH decreases and is less than 7.25, the lactate / pyruvate ratio rises and the anion interval increases.

Kidney function

Before taking the drug and regularly during Reduxin Forte therapy, creatinine clearance should be determined: in individuals with normal renal function - at least 1 time per year, in elderly patients and patients with creatinine clearance at the lower normal range - 2–4 times per year.

Surgery

48 hours before the start of the planned surgical intervention, Reduxin Forte should be canceled. Treatment is resumed no earlier than 48 hours after the end of the operation and only if normal renal function is maintained.

Other directions

While taking Reduxin Forte, patients should continue to follow a diet that assumes an even intake of carbohydrates throughout the day. With overweight, it is recommended to adhere to a low-calorie diet (but not less than 1000 kcal per day).
The drug is used with caution simultaneously with oral hypoglycemic agents (repaglinide, sulfonylurea derivatives) or insulin. In order to control diabetes, it is recommended to regularly take appropriate tests.
Reduxin Forte is prescribed only in case of insufficient effectiveness of all other non-drug methods of weight loss (if within three months it was possible to lose weight by only 5 kg or less).
The drug is used as part of complex therapy, which includes a change in lifestyle and diet, as well as an increase in physical activity. It is necessary to create the prerequisites for a persistent change in lifestyle and eating behavior, which will allow to maintain the achieved reduction in body weight after the abolition of drug treatment.
In addition to monitoring renal function, heart rate and blood pressure should be regularly measured. In the first 3 months, these parameters are monitored once every 2 weeks, then once every 4 weeks. If during two consecutive measurements, the resting heart rate is increased by 10 beats per minute or more, and the systolic / diastolic pressure is 10 mm Hg. Art. or more, you should stop taking Reduxin Forte.
In people with arterial hypertension (with a pressure of more than 145/90 mm Hg. Art. Against the background of antihypertensive therapy), heart rate and blood pressure are monitored more often and more carefully. If, in two consecutive measurements, blood pressure exceeds 145/90 mm Hg. Art., the treatment is suspended.
In sleep apnea syndrome, blood pressure is monitored especially carefully.
During a regular medical examination, special attention should be paid to chest pain, progressive dyspnea and swelling in the legs, as these symptoms may indicate the development of primary pulmonary hypertension.
If the patient forgot to take the next dose, it can not be doubled at the next dose. It is recommended to continue treatment according to the previously prescribed scheme.
There is no data on addiction to sibutramine, but despite this, it is recommended to study the patient's history and find out if there were any cases of drug dependence.
Metformin is recommended for the prevention of type 2 diabetes mellitus in patients with prediabetes and the presence of one or more risk factors for developing apparent type 2 diabetes mellitus (body mass index> 30 kg / m2, age up to 60 years, family history of diabetes in parents, arterial hypertension a history of gestational diabetes, low cholesterol of high density lipoproteins, increased concentration of triglycerides in the blood).

Influence on the ability to drive vehicles and complex mechanisms

Taking Reduxin Forte may limit the psychomotor abilities of the patient, therefore, during treatment it is recommended to be careful when driving or using other vehicles, and when working with complex and potentially dangerous mechanisms.

Pregnancy and lactation

Reduxin Forte is contraindicated during pregnancy, since today there are not enough studies confirming the safety of sibutramine for the fetus.
Women of childbearing age who are taking Reduxin Forte should use reliable methods of contraception.
The drug is contraindicated during breastfeeding.

Use in childhood

In children and adolescents under the age of 18, Reduxin Forte is not used.

With impaired renal function

The drug is contraindicated in patients with impaired renal function (with creatinine clearance less than 45 ml / min). If the creatinine clearance value is 45–59 ml / min, Reduxin Forte is taken with caution.

With impaired liver function

Reduxin Forte is contraindicated in patients with impaired liver function.

Use in old age

For elderly people aged 60–65 years, Reduxin Forte is prescribed with caution, but for people over 65 years of age it is not used.

Drug interaction

Metformin

The simultaneous use of metformin and iodine-containing radiopaque agents is contraindicated (the risk of lactic acidosis increases).
Co-administration with alcohol and drugs containing ethanol is not recommended.
Metformin is used with caution in combination with the following substances:
    Danazolum: development of hyperglycemia is possible (after the end of Danazolum therapy the dose of metformin must be adjusted);
    chlorpromazine: in doses of more than 100 mg per day, increases blood glucose by reducing the release of insulin;
    systemic and local glucocorticosteroids: reduced glucose tolerance develops, blood glucose levels increase, in some cases ketosis occurs;
    diuretics: loop diuretics increase the risk of lactic acidosis;
    injectable beta2-adrenergic agonists: due to stimulation of beta2-adrenergic receptors, blood glucose levels increase (glucose concentration must be controlled);
    antihypertensive drugs, including angiotensin converting enzyme inhibitors: a decrease in blood glucose levels may be necessary (dose adjustment of metformin may be required);
    cimetidine, ranolazine, vandetanib, dolutegravir, trimethoprim, isavukonazole: the rate of excretion of metformin decreases and its concentration in the blood increases;
    nifedipine: increased absorption and maximum plasma concentration of metformin;
    estrogens, phenothiazides, oral contraceptives, sympathomimetics, slow calcium channel blockers, glucagon, nicotinic acid, phenytoin, levothyroxine sodium, isoniazid: a decrease in the hypoglycemic effect of metformin is possible;
    cationic drugs (morphine, quinidine, ranitidine, trimethoprim, amiloride, procainamide, triamteren, vancomycin, digoxin, quinine): an increase in the maximum plasma concentration of metformin is possible (due to competition for tubular transport systems);
    acarbose, insulin, sulfonylurea derivatives, salicylates: hypoglycemia may develop;
    rifampicin: may increase the absorption of metformin and increase its hypoglycemic effect;
    verapamil, olaparib, krizotinib: a decrease in the hypoglycemic effect of metformin is possible.
Metformin does not alter the pharmacokinetics of ibuprofen and propranolol; may decrease the therapeutic effect of indirect anticoagulants.

Sibutramine

Microsomal oxidation inhibitors (e.g., cyclosporine, erythromycin and ketoconazole) increase the plasma concentration of active metabolites of sibutramine, which leads to an increase in heart rate and a clinically insignificant lengthening of the QT interval on the electrocardiogram.
With simultaneous use with macrolide antibiotics, carbamazepine, dexamethasone, phenytoin, rifampicin and phenobarbital, acceleration of sibutramine metabolism is possible.
The combined use of several drugs that increase the plasma concentration of serotonin can lead to a serious interaction. In rare cases, serotonin syndrome develops with a combination of sibutramine with potent analgesics (pethidine, pentazocine, fentanyl), selective serotonin reuptake inhibitors (used to treat depression), antitussive drugs (for example, dextromethorphan), and some medications used for migraines (migraine sumatriptan).
Despite the fact that sibutramine does not enhance the negative effect on the body of alcohol, they are not recommended to be taken at the same time (alcohol is contraindicated in compliance with the diet).
Sibutramine does not affect contraceptives for oral administration. When combined with drugs that affect platelet function or hemostasis, the risk of bleeding increases.
Sibutramine is prescribed with caution simultaneously with drugs that can increase heart rate and increase blood pressure (antiallergic, antitussive, and anti-cold medicines containing pseudoephedrine or ephedrine).
Co-administration of sibutramine with drugs for the treatment of mental disorders and drugs for weight loss, the mechanism of action of which is associated with an effect on the central nervous system, is contraindicated.

Terms and conditions of storage

Keep out of the reach of children. Store in a dark, dry place at a temperature not exceeding 25 ° C.
Shelf life is 3 years.

Reduxin Forte reviews

To date, there are very few reviews of Reduxin Forte, but according to reports, it can be concluded that the drug is an effective tool in the fight against extra pounds. Girls and women who use diet pills note that during treatment their appetite decreases and their sense of fullness comes faster. This helps to maintain a diet and, as a result, lose weight faster.
The main drawback, according to users, is the high cost of the tablets.

Terms of sell

You don't need a prescription to buy Reduxin Forte.