Slimia (Capsules) Instructions for Use

ATC Code

A08AA10 (Sibutramine)

Active Substance

Sibutramine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug for the treatment of centrally-acting obesity

Pharmacotherapeutic Group

Remedy for obesity

Pharmacological Action

A centrally-acting agent for the treatment of obesity. The mechanism of action is due to selective inhibition of the reuptake of serotonin and norepinephrine, and to a lesser extent, dopamine. It accelerates the onset and prolongs the feeling of satiety, which leads to a reduction in food intake. It increases energy expenditure by stimulating thermogenesis through the mediated activation of β₃-adrenergic receptors. It acts on both sides of the energy balance and contributes to weight loss.

Sibutramine and its metabolites do not release monoamines and are not MAO inhibitors; they do not have affinity for serotonergic, adrenergic, dopaminergic, muscarinic, histaminergic, benzodiazepine, and NMDA receptors.

Pharmacokinetics

After oral administration, Sibutramine is rapidly absorbed from the gastrointestinal tract. It is almost completely metabolized in the liver with the participation of cytochrome CYP3A4 isoenzymes to form mono- (desmethylsibutramine) and di-desmethyl (di-desmethylsibutramine) forms of active metabolites (M1 and M2), as well as by hydroxylation and conjugation to form inactive metabolites. The C_max of sibutramine is reached in 1.2 hours, and that of M1 and M2 in 3-4 hours. The C_max of M1 and M2 after a single oral dose of 15 mg is 4 ng/ml (3.2-4.8 ng/ml) and 6.4 ng/ml (5.6-7.2 ng/ml), respectively. Taking with food increases the time to reach C_max and reduces the C_max of desmethyl metabolites by 3 hours and 30%, respectively; it does not affect the AUC of desmethyl metabolites. It is rapidly and well distributed in tissues. Plasma protein binding: Sibutramine – 97%, M1 and M2 – 94%. The T_1/2 of sibutramine is 1.1 hours, M1 – 14 hours, M2 – 16 hours. It is excreted mainly by the kidneys as inactive metabolites.

In renal insufficiency, the main pharmacokinetic parameters (C_max, T_1/2, AUC) of sibutramine and its active metabolites do not change significantly.

Indications

As part of maintenance complex therapy for patients with excess body weight in alimentary obesity with a BMI of 30 kg/m² or more, and in alimentary obesity with a BMI of 27 kg/m² or more in the presence of other risk factors due to excess body weight, including type 2 diabetes mellitus (non-insulin dependent) or hyperlipidemia.

ICD codes

Dosage Regimen

Capsules

The initial dose is 10 mg/day. If the effectiveness is insufficient at this dose (weight loss of less than 2 kg over 4 weeks) and if well tolerated, the dose can be increased to 15 mg/day.

If there is no effect at a dose of 15 mg/day (weight loss of less than 2 kg over 4 weeks), Sibutramine should be discontinued.

In patients who respond inadequately to the therapy, i.e., those who fail to achieve a 5% reduction in body weight from the initial level within 3 months, the duration of use should not exceed 3 months.

The course of treatment should not exceed 1 year, as there are no data on the efficacy and safety of longer use.

Treatment should not be continued if, after the achieved weight loss, the patient regains 3 kg or more during further therapy.

Adverse Reactions

From the digestive system frequently – loss of appetite, constipation, dry mouth, nausea, transient increase in liver enzyme activity.

From the CNS and peripheral nervous system insomnia, headache, dizziness, anxiety, paresthesia, increased sweating, taste change, convulsive seizures; in one patient with a schizoaffective disorder, which presumably existed before the start of sibutramine therapy, acute psychosis developed after treatment.

From the cardiovascular system tachycardia, palpitation, increased blood pressure (moderate increase in resting blood pressure by 1-3 mm Hg and a moderate increase in pulse by 3-7 beats/min), vasodilation (reddening of the skin with a feeling of warmth), exacerbation of hemorrhoids; in some cases – a more pronounced increase in blood pressure and increased heart rate.

From the urinary system in isolated cases – acute interstitial nephritis, mesangiocapillary glomerulonephritis.

From the blood coagulation system thrombocytopenia, Henoch-Schönlein purpura.

Adverse effects most often occur at the beginning of therapy (in the first 4 weeks), their severity and frequency decrease over time.

Contraindications

Organic cause of obesity, known and established serious eating disorders (anorexia nervosa or bulimia nervosa), mental illness, Tourette’s syndrome, coronary artery disease, chronic heart failure in the stage of decompensation, congenital heart defects, occlusive peripheral arterial diseases, tachycardias, arrhythmias, cerebrovascular disorders (including transient ones), uncontrolled arterial hypertension (BP more than 145/90 mm Hg), hyperthyroidism, severe renal impairment, severe hepatic impairment, benign prostatic hyperplasia with residual urine formation, pheochromocytoma, glaucoma, established pharmacological drug and alcohol dependence, pregnancy, lactation (breastfeeding), simultaneous use or period up to 2 weeks after discontinuation of MAO inhibitors or other drugs that have a depressant effect on the CNS (antidepressants, antipsychotics, tryptophan) or other weight loss medications, hypersensitivity to sibutramine.

Use in Pregnancy and Lactation

Sibutramine is contraindicated for use during pregnancy and lactation (breastfeeding).

Women of childbearing age should use adequate contraceptive methods during treatment.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment.

Use with caution in patients with mild to moderate hepatic impairment (since asymptomatic increase in sibutramine plasma concentration is possible).

Use in Renal Impairment

Contraindicated in severe renal impairment.

Use with caution in patients with mild to moderate renal impairment (since inactive metabolites are partially excreted by the kidneys).

Pediatric Use

Should not be used in children and adolescents under 18 years of age due to the lack of sufficient clinical experience in this category of patients.

Geriatric Use

Not used in persons over 65 years of age due to the lack of sufficient clinical experience with the use of sibutramine in geriatrics.

Special Precautions

Use only in cases where all weight loss measures are ineffective (i.e., weight loss is less than 5 kg within 3 months).

Treatment should be carried out only within the framework of complex weight loss therapy under the supervision of a physician with practical experience in the treatment of obesity. Complex therapy includes both changes in diet and lifestyle, as well as increased physical activity. This creates the prerequisites for a lasting change in eating habits and lifestyle, which are necessary to maintain the achieved weight loss after discontinuation of drug therapy.

Use with caution concomitantly with drugs that increase the QT interval, in patients with hypokalemia and hypomagnesemia, epilepsy, with mild to moderate hepatic impairment (since asymptomatic increase in sibutramine plasma concentration is possible), with mild to moderate renal impairment (since inactive metabolites are partially excreted by the kidneys), in patients with a family history of motor tics or vocalisms, concomitantly with drugs that increase blood pressure and heart rate (including medications used for cough, allergies, and colds).

Not used in persons over 65 years of age due to the lack of sufficient clinical experience with the use of sibutramine in geriatrics.

During treatment, blood pressure and heart rate should be monitored: in the first 2 months of therapy – every 2 weeks, then monthly. In patients with arterial hypertension (BP more than 145/90 mm Hg), these parameters should be monitored especially carefully and, if necessary, more frequently. If blood pressure, upon repeated measurement, exceeded 145/90 mm Hg twice, then Sibutramine should be discontinued.

During regular medical monitoring during treatment, attention should be paid to progressive dyspnea, chest pain, and edema, although a connection between taking sibutramine and the development of primary pulmonary hypertension has not been established.

Withdrawal reactions to sibutramine (headache, increased appetite) are rare.

Alcohol should not be consumed during treatment due to the need to follow a diet.

Should not be used in children and adolescents under 18 years of age due to the lack of sufficient clinical experience in this category of patients.

Effect on the ability to drive vehicles and operate machinery

The effect of sibutramine on the ability to engage in potentially hazardous activities has not been currently established. However, the possibility of such an effect cannot be excluded. Use with caution in patients whose activities require increased attention and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with agents that inhibit the activity of the CYP3A4 isoenzyme (ketoconazole, erythromycin, troleandomycin, cyclosporine), the plasma concentrations of sibutramine metabolites increase, and the QT interval slightly increases.

With simultaneous use with rifampicin, phenytoin, carbamazepine, phenobarbital, dexamethasone, macrolide antibiotics, an acceleration of sibutramine metabolism is possible.

With simultaneous use with selective serotonin reuptake inhibitors (with citalopram, fluoxetine, paroxetine, sertraline), 5-HT₁ receptor agonists, ergot alkaloid derivatives, opioid analgesics, centrally-acting antitussives, the risk of developing serotonin syndrome increases.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.