GOLDLINE PLUS CAPSULES 10MG + 158.5MG

Hard gelatin capsules, the body of the capsule is white or almost white in color, the cap is blue. Capsule contents - powder or compacted powder mass of white or almost white color.

Composition

Active substances:

Sibutramine hydrochloride monohydrate, microcrystalline cellulose,

Excipients: Calcium stearate - 1.5 mg. The composition of the capsule shell: Cap: dye azoruby (E122) - 0.0570%; indigo carmine (Е132) - 0.3079%; sodium lauryl sulfate - 0.0800%; titanium dioxide - 1.0000%; gelatin - up to 100%.

sodium lauryl sulfate - 0.0800%; titanium dioxide - 2.0000%; gelatin - up to 100%,

Mechanism of action

Goldline® PLUS is a combination drug whose effect is due to its constituent components. Sibutramine is a prodrug and exerts its action in vivo due to metabolites (primary and secondary amines) that inhibit the reuptake of monoamines (serotonin, norepinephrine, 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 saturation and a reduction in the need for food, as well as an increase in thermal production.Indirectly activating betaz-adrenoreceptors, sibutramine acts on brown adipose tissue. A decrease in body weight is accompanied by an increase in plasma concentration of high-density lipoprotein (HDL) and a decrease in the amount of triglycerides, total cholesterol, low-density lipoprotein (LDL) and uric acid. Sibutramine and its metabolites do not affect the release of monoamines, do not inhibit monoamine oxidase (MAO); have a low affinity for a large number of neurotransmitter receptors, including serotonin (5-HTi, 5-HTia, 5-HTm, b-HTV), adrenergic (beta beta, betaz, alpha], alpha), dopamine (Di, D2), muscarinic, histamine (Hi), benzodiazepine and glutamate (NMDA) receptors. Microcrystalline cellulose 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.

Suction

After ingestion is rapidly absorbed from the gastrointestinal tract (GIT) by at least 77%. During “primary passage” through the liver, it undergoes biotransformation under the influence of CYP3A4 isoenzyme with the formation of two active metabolites (monodesmethylsibutramine (Ml) and didesmethylsibutramine (M2)).After taking a single dose of 15 mg, the maximum plasma concentration (Cmax) Ml is 4 ng / ml (3.2-4.8 ng / ml), M2 - 6.4 ng / ml (5.6-7.2 ng / ml). Stakh is reached in 1.2 hours (sibutramine), 3-4 hours (Ml and M2). Simultaneous ingestion lowers the Stach metabolites by 30% and increases the time it reaches 3 hours without changing the area of ​​the concentration-time curve (AUC).

It is quickly distributed on fabrics. Communication with proteins is 97% (sibutramine) and 94% (Ml and M2). The equilibrium concentration of active metabolites in the blood plasma is reached within 4 days after the start of use and approximately 2 times higher than the concentration in the blood plasma after taking a single dose.

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

The currently limited data do not indicate the existence of clinically significant differences in pharmacokinetics in men and women. Pharmacokinetics in elderly healthy individuals (mean age 70 years) is similar to that in young people.

Renal failure

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

Liver failure

Patients with moderate liver failure after a single dose of sibutramine AUC active metabolites of Ml and M2 are 24% higher than in healthy individuals.
Side effects
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 (> 10%), often (> 1%, but <10%).

Nervous system disorders: very frequent side effects are dry mouth and insomnia, headache, dizziness, anxiety, paresthesias, and a change in taste are often noted.

Heart disorders: tachycardia, palpitations are common. There is a moderate increase in heart rate of 3-7 beats per minute. In some cases, a more pronounced increase in heart rate is not excluded. Clinically significant changes in heart rate are recorded mainly at the beginning of treatment (in the first 4-8 weeks).

Violations of the blood vessels: often increased blood pressure, vasodilation. There is a moderate rise in blood pressure at rest at 1-3 mm Hg. st. In some cases, more pronounced increases in blood pressure are not excluded. Clinically significant changes in blood pressure are recorded mainly at the beginning of treatment (in the first 4-8 weeks).

Disorders of the gastrointestinal tract: loss of appetite and constipation, often nausea and exacerbation of hemorrhoids are often observed. With a tendency to constipation in the first days of the necessary control over the evacuation function of the intestine. When constipation occurs, they stop and take a laxative.

Disturbances of the skin and subcutaneous tissues: often increased sweating.

In rare cases with sibutramine treatment, 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, Shenlein-Henoch purpura (hemorrhage into the skin), convulsions, thrombocytopenia, transient increase in the activity of "liver" enzymes in the blood.

see section “Contraindications” and
"Special instructions".

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

Heart disorders: atrial fibrillation.

Immune system disorders: hypersensitivity reactions (from mild skin rash and urticaria to angioedema (angioedema) and anaphylaxis).

Mental disorders: psychosis, states of suicidally directed thinking, suicide, and mania. In the event of such conditions, the drug must be canceled.

Nervous system disorders: convulsions, short-term memory impairment.

Disturbances from the organ of vision: blurred vision ("the veil before the eyes"). Disorders of the gastrointestinal tract: Diarrhea, vomiting.

Violations of the skin and subcutaneous tissues: alopecia.

Kidney and urinary tract disorders: urinary retention.

Violations of the genital organs and the breast: a violation

ejaculation / orgasm, impotence, menstrual disorders, uterine bleeding.

Goldline® PLUS should be used only in cases where all non-drug weight loss measures are ineffective - if the weight loss for 3 months was less than 5 kg. Treatment with Goldline PLUS should be carried out as part of a comprehensive treatment for weight loss under the supervision of a physician who has practical experience in treating obesity. Combined therapy includes both a change in diet and lifestyle, and an increase in physical activity. An important component of therapy is the creation of prerequisites for persistent changes in eating behavior and lifestyle, which are necessary to maintain the achieved weight loss and after the abolition of drug therapy.As part of therapy with Goldline PLUS, patients need to change their lifestyle and habits in such a way as to ensure that the achieved weight loss is maintained after the completion of treatment. Patients should be clear about the fact that non-compliance with these requirements will lead to a repeated increase in body weight and repeated treatment to the attending physician. In patients taking Goldline PLUS, blood pressure and heart rate should be measured regularly. 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 the heart rate at rest> \ 000910 beats per minute or a systolic / diastolic pressure> 10 mmHg is detected. Art., you must stop treatment. In patients with arterial hypertension, in whom, against the background of antihypertensive therapy, blood pressure is higher than 145/90 mm Hg. Art., this control should be carried out very carefully and, if necessary, at shorter intervals.

In patients in whom blood pressure twice during repeated measurements exceeded the level of 145/90 mm Hg. Art., treatment with Goldline PLUS should be canceled (see section “Side Effects”).

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

Special attention requires the simultaneous appointment of drugs that increase the QT interval.These drugs include Hi-histamine blockers (astemizole, terfenadine); antiarrhythmic drugs that increase the QT interval (amiodarone, quinidine, flekainid, meksiletin, propafenone, sotalol); gastrointestinal motility stimulator cisapride; pimozide, sertindol and tricyclic antidepressants. This also applies to conditions that can lead to an increase in the QT interval, such as hypokalemia and hypomagnesemia (see also the section "Interaction with other drugs").

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

Although there is no link between taking sibutramine and the development of primary pulmonary hypertension, however, given the well-known risk of drugs in this group, regular medical monitoring requires special attention to symptoms such as progressive dyspnea (breathing disorder), chest pain and edema in the legs. .

When skipping a dose of Goldline PLUS drug, you should not take a double dose of the drug in the next dose, it is recommended to continue taking the drug as prescribed.

The duration of taking the drug Goldline PLUS should not exceed 1 year.

When co-administered with sibutramine and other serotonin reuptake inhibitors, there is an increased risk of bleeding. In patients who are predisposed to bleeding, as well as taking drugs that affect hemostasis or platelet function, sibutramine should be used with caution.

Although there are no clinical data on the addiction to sibutramine, it should be ascertained whether there were any cases of drug dependence in the patient’s history and to pay attention to possible signs of drug abuse.

Impact on ability to drive vehicles and mechanisms Taking Goldline PLUS can limit the ability to drive vehicles and mechanisms. During the period of use of the drug Goldline® PLUS, care should be taken when driving and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

• Goldline® PLUS is indicated for weight loss in the following conditions:
• alimentary obesity with a body mass index (BMI) of 30 kg / m and more;
• alimentary obesity with a body mass index of 27 km / m2 or more in combination with type 2 diabetes mellitus and dyslipidemia.

established hypersensitivity to sibutramine or to other components of the drug;
the presence of organic causes of obesity (eg, hypothyroidism);
severe eating disorders - anorexia nervosa or bulimia nervosa;
mental illness;
Gilles de la Tourette syndrome (generalized tics);

simultaneous administration of MAO inhibitors (for example, phentermine, fenfluramine, dexfenfluramine, ethylamphetamine,ephedrine) or use within 2 weeks before taking the drug Goldline PLUS and 2 weeks after the end of his reception of other drugs acting on the central nervous system, inhibiting serotonin reuptake (for example, antidepressants, neuroleptics); sleeping pills containing tryptophan, as well as other centrally acting drugs for weight loss or for the treatment of mental disorders;

cardiovascular diseases (in the anamnesis or at present): coronary heart disease (myocardial infarction (MI), angina); chronic heart failure in the stage of decompensation, occlusive peripheral arterial disease, tachycardia, arrhythmia, cerebrovascular disease (stroke, transient disorders of cerebral circulation);

uncontrolled arterial hypertension (arterial pressure (BP) above 145/90 mm Hg) (see also the section "Special Instructions");

angle-closure glaucoma;

thyrotoxicosis;

severe violations of the liver and / or kidneys;

benign prostatic hyperplasia;

pheochromocytoma;

established pharmacological, drug or alcohol dependence;

pregnancy and breastfeeding;

age up to 18 years and over 65 years.

Precautions should be prescribed the drug in the following conditions: arrhythmias in history, chronic circulatory failure, coronary artery disease (includingin history), except for coronary heart disease (MI, angina); glaucoma, except for angle-closure glaucoma, cholelithiasis, arterial hypertension (controlled and history), neurological disorders, including mental retardation and convulsions (including history), epilepsy, impaired function of the liver and / or mild to moderate kidneys, ^ motor and verbal tics in history, tendency to bleeding, impaired blood clotting, taking drugs that affect hemostasis or platelet function.

Since so far there is not a sufficiently large number of studies regarding the safety of exposure of sibutramine to the fetus, this drug is contraindicated during pregnancy. Women who are in reproductive age should use contraceptives while taking Goldline PLUS.

It is contraindicated to take the drug G Oldline® PLUS during breastfeeding.

Inhibitors of microsomal oxidation, incl. CYP3A4 isoenzyme inhibitors (ketoconazole, Erythromycin, cyclosporin, etc.) increase the concentration of sibutramine metabolites in the blood plasma 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 sibutramine metabolism.The simultaneous use of several drugs that increase the serotonin content in the blood plasma, can lead to the development of a serious interaction. The so-called serotonin syndrome can develop in rare cases with simultaneous use of sibutramine with selective serotonin reuptake inhibitors (drugs for the treatment of depression), with some drugs for the treatment of migraine (sumatriptan, dihydroergotamine), with potent analgesics (pentazine, petidine, fidin. antitussive drugs (dextromethorphan). Sibutramine does not affect the action of oral contraceptives.

While taking sibutramine and alcohol, there was no marked increase in the negative effect of alcohol. However, alcohol is absolutely not combined with the recommended dietary measures when taking sibutramine.

The simultaneous use of sibutramine with other drugs that affect hemostasis or platelet function increases the risk of bleeding. Drug interaction with simultaneous use of sibutramine with drugs that increase blood pressure and heart rate, is currently not fully understood. This group of drugs includes decongestants, cold, cough and antiallergic drugs, which include ephedrine or pseudoephedrine. Therefore, in cases of simultaneous administration of these drugs with sibutramine, caution should be exercised.The combined use of sibutramine with drugs for weight loss, acting on the central nervous system, or drugs for the treatment of mental disorders is contraindicated.