MERIDIA

Active material: Siʙutramin
When ATH: A08AA10
CCF: Anti-obesity medication centrally acting
ICD-10 codes (testimony): E66
When CSF: 16.02.01
Manufacturer: ABBOTT GmbH & Co. KG (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Capsules hard gelatin, with a yellow body and a blue Cap, overprinted “10”; contents of capsules – white or almost white, easy loose powder.

Excipients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, indigodin (E132), Titanium dioxide (E171), sodium lauryl, ink (grey), quinoline yellow.

7 PC. – packings Valium planimetric (2) – packs cardboard.
14 PC. – packings Valium planimetric (1) – packs cardboard.
14 PC. – packings Valium planimetric (2) – packs cardboard.
14 PC. – packings Valium planimetric (6) – packs cardboard.

Capsules hard gelatin, with a white hull and blue Cap, overprinted “15”; contents of capsules – white or almost white, easy loose powder.

Excipients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, indigotin (E132), Titanium dioxide (E171), gelatin, sodium lauryl, ink (grey), quinoline yellow.

7 PC. – packings Valium planimetric (2) – packs cardboard.
14 PC. – packings Valium planimetric (1) – packs cardboard.
14 PC. – packings Valium planimetric (2) – packs cardboard.
14 PC. – packings Valium planimetric (6) – packs cardboard.

Pharmacological action

Anti-obesity medication. Sibutramine is a prodrug and exerts its effect in vivo due to metabolites (primary and secondary amines), inhibiting the reuptake of monoamines (primarily serotonin and norepinephrine). Increase in neurotransmission neurotransmitters increases the activity of Central 5-HT serotonin and adrenergic receptors, which increases satiety and reduce the need for food, as well as an increase in termoproduktsii. Опосредованно активируя b₃-adrenoreceptory, Sibutramine acts on brown adipose tissue.

Sibutramine and its metabolites do not affect the release of monoamines, not inhibit MAO; It has no affinity to a large number of neurotransmitter receptors, including serotonin (5-HT₁, 5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2C), adrenergic (b₁, b₂, b₃, a₁, a₂), dopamine (D₁, D₂), muscarinic, histamine (H₁), benzodiazepine and NMDA-receptors.

Pharmacokinetics

Absorption, distribution, metabolism

After oral administration of sibutramine is rapidly absorbed from the gastrointestinal tract. The time to reach C_max sibutramine is 1.2 no. Sibutramine is almost completely metabolized in the liver, with the participation of izofermenta CYP 3A4 with the formation of Mono- (dismetilsibutramin) and di-dismetil (di-dismetilsibutramin) Forms active metabolites (M1 and M2), as well as by gidrauxilirovania and conjugating with the formation of active metabolites. After receiving a single oral dose of the drug 15 mg C_max M1 and M2 is 4 ng / ml (3.2-4.8 ng / ml) and 6.4 ng / ml (5.6-7.2 ng / ml) respectively. Reception with food increases the achievement and reduces the amount of C_max dismetil metabolites 3 and h 30% respectively, does not affect the value of the AUC dismetil metabolites. Quickly and well distributed in the tissues. Binding protein with sibutramine – 97%, M1 and M2 – 94%.

Deduction

T_1/2 siʙutramina – 1.1 no, M1 – 14 no, M2 – 16 no. Write mainly kidneys as inactive metabolites.

Pharmacokinetics in special clinical situations

When kidney failure basic pharmacokinetic parameters (C_max, T_1/2 и AUC) do not change significantly.

Testimony

- Alimentary obesity with a body mass index (BMI) 30 kg / m² and more;

- Alimentary obesity with a BMI 27 kg / m² and more combined with diabetes mellitus type 2 (insulinnezavisimym) or dislipoproteinemiej.

Dosage regimen

Dose set individually, depending on tolerability and clinical efficacy.

The initial dose is 10 mg. With the lack of efficiency (reduce body weight less than 2 kg per 4 of the week), but with good endurance daily dose can be increased to 15 mg. If after increasing the dose of the drug remains insufficient (reduce body weight less than 2 kg per 4 of the week), continued treatment is inappropriate.

Meridia Capsules^® It should be taken in the morning, not chewing and drinking plenty of fluids (glass of water). The drug can be taken on an empty stomach, and combine with a meal.

Do not continue treatment more 3 MO patients, that during this time (3 Months) It was not possible to achieve lower body mass index in 5% from baseline. Treatment should not continue, If a therapy Meridia after achieved lower body mass index patient gains weight 3 kg or more.

Duration of treatment Meridia^® should not exceed 2 year, as for a more prolonged period of dose data on efficacy and safety of missing.

Side effect

The most common side effects occur early in treatment (first 4 of the week). Their severity and frequency over time, weaken. Side effects are, usually, light and reversible.

Side effects, Depending on the impact on organs and systems, are presented in the following order: often – >10%, sometimes – 1-10%, rarely – <1%.

From the central and peripheral nervous system: often – insomnia, sometimes – headache, dizziness, anxiety, paresthesia, change in taste.

Cardio-vascular system: sometimes – tachycardia (increased heart rate at 3-7 u. / min), palpitations, increased blood pressure (alone on the 1-3 mmHg.), vasodilation. In some cases, are not excluded more severe increase in blood pressure and heart rate. Clinically significant changes in the levels of HELL and HEART RATE recorded mainly at the beginning of treatment (first 4-8 weeks).

Digestive system: often – dry mouth, loss of appetite, constipation; sometimes – nausea, aggravation of hemorrhoids.

Other: sometimes – increased sweating.

In rare cases, Describes the following clinically important side effects: dysmenorrhoea, swelling, flu-like symptoms, itchy skin, backache, abdominal pain, paradoxical increased appetite, thirst, rhinitis, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, acute interstitial nephritis, bleeding, purpura Shenleyna-Genoa, convulsions, thrombocytopenia, transient increase in liver enzymes in the blood plasma.

One patient with schizoaffective violation, which presumably existed prior to treatment, after treatment developed acute psychosis.

Contraindications

- Availability of organic causes of obesity (eg, gipotireoz);

-serious eating disorders (anorexia nervosa or bulimia nervosa);

- Mental illness;

— Gilles de la Tourette Syndrome (chronic generalized teak);

- Simultaneous MAO inhibitors (eg, phentermine, fenfluramina, dexfenfluramine, ethylamphetamine, ephedrine) or their use for 2 weeks before the appointment of Meridia; serotonin reuptake inhibitors; sleeping pills; preparations, containing tryptophan; other preparations central action to reduce body weight;

- CHD, chronic cardiac insufficiency of the decompensation, congenital heart disease, occlusive peripheral arterial disease, tachycardia, arrhythmia, cerebrovascular diseases (stroke, transient ischemic attacks);

- Uncontrolled hypertension (BP above 145/90 mmHg.);

- Thyrotoxicosis;

- Severe liver and / or kidney;

- Benign prostatic hyperplasia;

- Pheochromocytoma;

- Zakrыtougolynaya glaucoma;

- Established drug, drug or alcohol dependence;

- Pregnancy;

- Lactation (breast-feeding);

- Childhood and adolescence up 18 years;

-age over 65 years;

-hypersensitivity to sibutraminu or to other components of the drug.

Carefully should designate product in aritmiah history, chronic heart failure, diseases of the coronary arteries (incl. history), cholelithiasis, hypertension (controlled and history), Neurological violations (including mental retardation and seizures (incl. history), violations of the liver and/or kidney disease mild, motor and verbal tics in history.

Pregnancy and lactation

You should not take the drug Meridia^® Pregnancy and lactation (breast-feeding), because so far there is not enough research on security impact of Meridia^® on the fetus.

Women of childbearing age, receiving the drug Meridia^®, should use methods of contraception.

Cautions

Drug Meridia^® It should be applied only in cases, When non-drug interventions to reduce body weight (diet and physical activity) ineffective (decrease in body weight during 3 months amounted to less 5 kg).

Medication Meridia^® It must be carried out within the framework of complex therapy for weight loss under medical supervision, have practical experience in the treatment of obesity. Integrated therapy includes how to change eating habits and lifestyles, and increased physical activity. Patients should change their lifestyles and habits so, After completion of treatment to ensure that made reducing body weight. Patients need to be clear about, that failure to do so will lead to an increase in body weight and the need for re-treatment.

During the period of administration of the drug Meridia^® It is necessary to monitor the level of HELL and HR: first 2 of the month – every 2 of the week, and then monthly. In patients with arterial hypertension control must be implemented carefully and over shorter intervals. If the control measurement of HELL twice exceeded the level of 145/90 mmHg., reception of Meridia^® should be suspended.

The caution should appoint Meridia^® simultaneously with drugs, prolonging the QT interval, incl. blokatorami gistaminovykh H₁-receptors (astemizol, terfenadine), antiarrhythmic drugs (Amiodarone, quinidine, flekainid, mexiletine, propafenone, sotalol), cizapridom, pimozidom, sertindolom and tricyclic antidepressants. This also applies to the States, that can lead to longer QT interval (eg, gipomagniemiya).

The interval between receiving MAO inhibitors (incl. furazolidona, procarbazine, selegiline) and Meridia^® must be at least 2 weeks.

Although it did not establish a link between taking sibutramina and development of primary pulmonary hypertension, However, in applying the drug Meridia^® It is necessary to pay attention to the appearance of progressive respiratory failure, chest pain and swelling in the legs.

In case of skipping the dose of Meridia^® should not be taken at the following reception of a double dose of this medication, It is recommended that you continue to accept further drug scheme.

Reaction to the lifting of the drug (headache, increased appetite) are rare. There is no evidence, that is observed after the drug withdrawal syndrome, withdrawal or mood disorders.

During the period of administration of the drug should not take alcoholic drinks, tk. alcohol is absolutely not combined with recommended when taking Meridia^® dietary interventions.

Impact on the ability to drive vehicles and ypravleniju mechanisms

Preparations, influence on the central nervous system, may limit the mental activity, memory and speed of reactions. And although studies sibutramine does not affect these functions, Nevertheless, taking the drug Meridia^® may limit the ability to drive vehicles and management mechanisms.

Overdose

There are very limited data about overdose sibutramine. Specific signs of an overdose are not known, Nonetheless, should take into account the possibility of a more pronounced manifestations of side effects. The patient should notify the attending physician in case of alleged overdose.

Treatment: There are no specific antidotes; should provide free breathing, monitor the state of the cardiovascular system, if necessary, symptomatic therapy. Viewed the appointment of activated carbon, gastric lavage, with an increase in blood pressure and tachycardia – beta-blockers. The effectiveness of forced diuresis or hemodialysis is not installed.

Drug Interactions

Simultaneous reception Meridia^® with inhibitors izofermenta CYP3A4 (ketoconazole, Erythromycin, troleandomiцin, cyclosporine) leads to increased concentrations of metabolites of sibutramine with increased HR and clinically insignificant elongation QT interval.

Rifampicin, macrolide antibiotics, phenytoin, Carbamazepine, phenobarbital and dexamethasone may accelerate the metabolism of sibutramine.

Together with the use of Meridia^® with selective serotonin reuptake inhibitors (antidepressants), with drugs for the treatment of migraine (sumatriptan, digidroergotamin), with potent analgesics (pentazocin, pethidine, Fentanyl), with protivokashlevami drugs (dextromethorphan) in rare cases may develop serotonin syndrome.

Patient interaction drug Meridia^® with drugs, raising HELL and HR, with protivokashlevami, anti-allergic drugs currently insufficiently studied.

Meridia^® does not affect the action of oral contraceptives.

While receiving sibutramine and ethanol were observed strengthening the last.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a dry, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 3 year.