Miracitol - instructions for use, dose, side effects, contraindications

Excipients: croscarmellose sodium 4,5 / 9,0 mg, microcrystalline cellulose 100.0 / 200.0 mg, silicon dioxide colloid 1.475 / 2.95 mg, talc 5.0 / 10.0 mg, magnesium stearate 1.25 / 2.5 mg;

film sheath: opadray II 85 F18422 white (polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide 3.0 / 5.0 mg.

Description:

Oval tablets covered with a film shell, white with a risk on one side.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.B.10 Escitalopram

Pharmacodynamics:

Escitalopram is an antidepressant, a selective serotonin reuptake inhibitor (SSRI). Inhibition of reuptake of serotonin leads to an increase in the concentration of this neurotransmitter in the synaptic cleft, enhances and prolongs its effect on postsynaptic receptor sites. Escitalopram has no or very little ability to bind to a number of receptors, including: serotonin 5-HT_1A, 5-HT₂receptors, dopamine D₁ and D₂ receptors, α₁-, α₂-, β-adrenergic receptors, histamine H₁muscarinic cholinergic, benzodiazepine and opiate receptors.

Pharmacokinetics:

Absorption is not dependent on food intake. Bioavailability of escitalopram is about 80%. The mean time to reach the maximum concentration in the blood plasma (T_mOh) is about 4 hours after repeated use. Apparent volume of distribution (V_d_,_β/F) after oral administration is from 12 to 26 l / kg. The binding of escitalopram and its major metabolites with blood plasma proteins is below 80%. Escitalopram is metabolized in the liver to demethylated and demodetylated metabolites. They are both pharmacologically active.The basic substance and its metabolites are partially isolated in the form of glucuronides.

After repeated use, the average concentration of demethyl- and didemethyl metabolites is usually 28-31% and less than 5%, respectively, of the concentration of escitalopram. Biotransformation of escitalopram to the demethylated metabolite occurs mainly through the use of an isoenzyme CYP2C19. Some participation of isoenzymes is possible CYP3A4 and CYP2D6. In persons with a weak isoenzyme activity CYP2C19 the concentration of escitalopram can be twice as high as in cases with high activity of this isoenzyme. Significant changes in drug concentration in cases with a weak isoenzyme activity CYP2D6 was not found.

The half-life (T_1/2) after repeated use is about 30 hours. Oral clearance (Cl_oral) is about 0.6 l / min. The main metabolites of escitalopram have a longer half-life. Escitalopram and its main metabolites are excreted by the liver (the metabolic pathway) and the kidneys. Most of it is excreted in the form of metabolites with urine.

The kinetics of escitalopram are linear.The equilibrium concentration (C_ss) is reached after about 1 week. Average C_ss 50 nmol / l (20 to 125 nmol / l) is achieved with a daily dose of 10 mg.

In elderly patients (over 65 years):

In the elderly (over 65) escitalopram is slower than in younger patients. The amount of the substance in the systemic circulation, calculated using the pharmacokinetic index, the area under the "concentration-time" curve (AUC) in the elderly is 50% greater than in young healthy volunteers (see section "Method of administration and dose").

Reduced Ffunction liver:

In patients with mild or moderate liver dysfunction (criteria Child-Pugh A and B), the half-life of escitalopram is approximately twice as long, a AUC approximately 60% higher than in patients with normal liver function (see section "Method of administration and dose").

Reduced Ffunction kidney:

In patients with reduced renal function (creatinine clearance (CL_cr 10-53 ml / min)) there is an elongation of the half-life and a slight increase AUC, in comparison with racemic citalopram. The concentration of metabolites in the blood plasma was not determined, but it is also likely to increase (see the section "Dosing and Administration").

Indications:

Depressive disorders of any severity.

Panic disorder with / without agoraphobia.

Contraindications:

Hypersensitivity, children's age, pregnancy, lactation, simultaneous appointment with monoamine oxidase (MAO) inhibitors, sumatriptan and other serotonergic drugs.

Carefully:

Presence of drug dependence (including history), hepatic and / or renal insufficiency, manic disorders, convulsive disorders, pregnancy, lactation period, advanced age, children's age (efficacy and safety of use not established); pharmacologically uncontrolled epilepsy, depression with suicidal attempts, diabetes mellitus, a tendency to bleeding; simultaneous reception with drugs that reduce the threshold of convulsive readiness, causing hyponatremia; ethanol; drugs metabolized with the participation of the isoenzyme system CYP2C19.

Pregnancy and lactation:

To date, there is no information on the use of escitalopram during pregnancy and lactation.

For this reason, the drug can only be prescribed to pregnant women in case of emergency, after a thorough analysis of the risk / benefit ratio.

Escitalopram penetrates into breast milk. Escitalopram should not be prescribed to nursing mothers and in the event of lactation, the drug should be immediately discontinued.

Dosing and Administration:

Inside.

Miracitol is prescribed to adults once a day, regardless of food intake.

Depressive disorders

Usually prescribe 10 mg once a day. Depending on the individual reaction of the patient, the dose may be increased to a maximum of 20 mg / day. The antidepressant effect usually develops in 2-4 weeks after the start of treatment. After the disappearance of the symptoms of depression, at least for another 6 months, it is necessary to continue therapy to fix the effect.

Panic disorder with or without agoraphobia

During the first week of treatment, a dose of 5 mg / day is recommended, which is then increased to 10 mg / day. Depending on the individual reaction of the patient, the dose may be increased to a maximum of 20 mg / day.

The maximum therapeutic effect is achieved approximately 3 months after the start of treatment. The therapy lasts for several months.

Elderly patients (over 65 years of age)

It is recommended to use half of the usually recommended dose (ie, only 5 mg / day) and a lower maximum dose (10 mg / day).

Decreased kidney function

With mild and moderate renal failure, dose adjustments are not required. Patients with severe renal insufficiency (creatinine clearance below 30 ml / min) should be prescribed Miratsitol with minimal therapeutic doses, gradually increasing them taking into account tolerability and efficacy.

Decreased liver function

The recommended initial dose for the first two weeks of treatment is 5 mg / day. Depending on the individual reaction of the patient, the dose may be increased to 10 mg / day.

Reduced activity of cytochrome CYP2C19

For patients with a weak isoenzyme activity CYP2C19 The recommended initial dose for the first two weeks of treatment is 5 mg / day. Depending on the individual reaction of the patient, the dose may be increased to 10 mg / day.

Discontinuation of treatment

When discontinuing treatment with miracitol, the dose should gradually decrease within 1-2 weeks in order to avoid the occurrence of the "withdrawal" syndrome.

Side effects:

Side effects most often occur at 1 or 2 weeks of treatment and then usually become less intense and occur less frequently with continued therapy.

From the nervous system: rare - asthenia, excessive fatigue, drowsiness or insomnia, anxiety, tremor, agitation, amnesia, apathy, extrapyramidal disorders, mood changes, aggressive behavior, hallucinations, depersonalization, emotional lability, euphoria, manic disorders, panic, psychotic disorders, serotonin syndrome agitation, confusion, diarrhea, hyperthermia, hyperreflexia, ataxia, tremor, increased sweating, agitation, uncontrolled behavior).

From the side of the digestive tract: rarely - dry mouth, nausea, vomiting, hypersalivation, flatulence, diarrhea, abdominal pain, anorexia.

From the cardiovascular system: rarely - bradycardia, lowering of arterial pressure, orthostatic hypotension, arrhythmia.

From the hematopoiesis: rarely - thrombocytopenia, bleeding.

From the sense organs: rarely - mydriasis, paresis of accommodation, a taste disorder.

On the part of the reproductive system: violation of sexual function - violation of ejaculation, decreased libido, impotence; menstrual cycle disorders.

Allergic reactions: skin rash, rarely - toxic epidermal necrolysis, rhinitis, sinusitis.

Other: rarely - hyperthermia, polyuria, mastodonia, galactorrhea, hyponatremia, violation of urination, arthralgia, myalgia, yawning, gnashing of teeth, increase or decrease in body weight, dyspnea.

In addition, after prolonged use, a sharp discontinuation of therapy with Miratsitol in some patients can lead to the emergence of the "withdrawal" syndrome. With a sharp discontinuation of escitalopram, unwanted reactions such as dizziness, headaches and nausea, which are not significant, and duration - are limited.

Overdose:

Symptoms: dizziness, tremor, agitation, increased perspiration, drowsiness, oppression of consciousness of varying severity, convulsions, sinus tachycardia, changes in ECG (segment change ST and the T wave, the expansion of the complex QRS, elongation QT interval), arrhythmia, ventricular arrhythmia, cyanosis, respiratory depression, vomiting, rhabdomyolysis, metabolic acidosis, hypokalemia, very rarely acute renal failure.

Treatment: there is no specific antidote. Treatment is symptomatic and supportive - gastric lavage, adequate oxygenation. Monitoring the function of the cardiovascular and respiratory systems.

Interaction:

Inhibitors of monoamine oxidase (MAO)

In patients taking selective serotonin reuptake inhibitors (SSRIs) in conjunction with monoamine oxidase (MAO) inhibitors, or in patients starting MAO inhibitors immediately after SSRI therapy, serious adverse reactions may occur. Escitalopram should not be administered in conjunction with MAO inhibitors. Treatment with escitalopram should be started 14 days after the cancellation of the course of irreversible MAO inhibitors and, at least 1 day after discontinuation of therapy with a reversible MAO inhibitor of type A - moclobemide. Treatment with escitalopram should be discontinued 7 days before treatment with MAO inhibitors.

Combinations of medicines requiring careful use:

Serotonergic drugs

Joint use with serotonergic drugs (eg tramadol,sumatriptan and other triptans) can lead to the development of serotonin syndrome.

Drugs that reduce the threshold of convulsive readiness

Miracitol can reduce the threshold of convulsive readiness. Therefore, care should be taken when concurrently prescribing other drugs that reduce the threshold of convulsive readiness (antidepressants (tricyclics, other SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion and tramadol).

Lithium, tryptophan

Miracitol enhances the pharmacological effects of tryptophan (increased serotonergic effect) and the toxic effects of lithium preparations.

Hypericum perforatum (St. John's wort pitted)

Simultaneous administration of SSRIs and preparations containing St. John's Wort (Hypericum perforatum), may lead to an increase in the number of side effects.

Anticoagulants and other drugs that affect blood coagulability

Violation of blood clotting can occur with the simultaneous administration of escitalopram with oral anticoagulants and other drugs that affect blood clotting (for example,atypical antipsychotic agents and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs, ticlopidine and dipyridamole). In such cases, blood coagulation monitoring is necessary.

Alcohol (ethanol)

Escitalopram does not enter with pharmacodynamic or pharmacokinetic interaction with alcohol. However, as with other psychotropic drugs, simultaneous use of escitalopram and alcohol is not recommended.

Pharmacokinetic interactions

Impact other drugs for the pharmacokinetics of escitalopram

Mainly escitalopram metabolized with the participation of isoenzymes CYP2C19, CYP3A4 and CYP2D6. Care should be taken when co-prescribing with inhibitors CYP2C19 (omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or with cimetidine. Joint use of escitalopram with omeprazole (inhibitor CYP2C19) with a single daily dose of 30 mg led to an increase (about 50%) of the concentration of escitalopram in blood plasma.Also, caution should be given to high doses of escitalopram simultaneously with high doses of cimetidine, a potent inhibitor of isoenzymes CYP2D6, CYP3A4 and CYP1A2. A decrease in the dose of escitalopram may be required depending on adverse reactions.

Effect of escitalopram on pharmacokinetics other medicines

Escitalopram is an inhibitor of the isoenzyme CYP2D6. Caution should be exercised when concomitant administration of escitalopram and drugs metabolized by this isoenzyme and having a small therapeutic index, for example, flecainide, propafenone and metoprolol (in cases of heart failure), or medicines, mainly metabolized by CYP2D6 and acting on the central nervous system, for example, antidepressants - desipramine, clomipramine, nortriptyline, or antipsychotic agents - risperidone, thioridazine, haloperidol. In these cases, dose adjustment may be required, as the concentration of escitalopram in the blood plasma increases.

Simultaneous administration of escitalopram and desipramine or metoprolol leads to a twofold increase in the concentration of the last two drugs, which should be taken into account when choosing doses.

Escitalopram may slightly inhibit the isoenzyme CYP2C19. Therefore, caution should be exercised while using escitalopram and medications that are metabolized CYP2C19.

Incompatibility

Not detected.

Special instructions:

The use of antidepressants, incl. escitalopram, especially in children, adolescents and young people under the age of 24, can lead to increased suicidal behavior. For this reason, especially at the beginning of the course of treatment and during the first months of treatment, with a change in the dose of the drug, either upward or downward, or when the drug is withdrawn, patients should be carefully monitored for suicidal behavior or other changes , such as agitation and / or irritability.

Paradoxical anxiety

In some patients with panic disorders, anxiety may occur at the onset of antidepressant treatment. In most cases, these paradoxical reactions take place within 2 weeks after initiation of therapy. To reduce the likelihood of anxiogenic effect, it is recommended to use low initial doses.

Convulsive Pregnancy

In the case of convulsive seizures, the drug should be immediately withdrawn. SSRIs should not be prescribed to patients with uncontrolled epilepsy; with controlled seizures careful monitoring is necessary. With an increase in the frequency of convulsive seizures of SSRIs, including escitalopram, should be canceled.

Mania

SSRIs should be used with caution in patients with manic disorders in history. With the development of the manic state escitalopram should be canceled.

Diabetes

In patients with diabetes mellitus, the treatment of SSRIs can alter the glucose level in the blood. Therefore, it may be necessary to adjust the dosages of insulin and / or oral hypoglycemic drugs.

Hyponatremia

When SSRIs were used, there were cases of hyponatremia, which is probably associated with a violation of the secretion of antidiuretic hormone (ADH). For this reason, SSRIs should be administered with caution to those at risk of developing hyponatremia: the elderly, the patient with cirrhosis and taking drugs that can cause hyponatraemia.

Hemorrhages

When SSRIs were used, cases of development of skin hemorrhages were observed: ecchymosis and purpura.It is necessary to use SSRIs with caution in patients with a tendency to bleeding, and also taking oral anticoagulants and drugs that affect blood clotting (for example, atypical antipsychotics and phenothiazine, most tricyclic antidepressants, acetylsalicylic acid and NSAIDs are nonsteroidal anti-inflammatory drugs).

ECT (electroconvulsive therapy)

Since the clinical experience of simultaneous application of SSRIs and ECT is limited, caution should be exercised in such cases.

Reversible, selective inhibitors of MAO type A

Combine escitalopram and MAO type A inhibitors are not recommended because of the risk of developing a serotonin syndrome.

See the "Drug Interactions" section for more details on the joint administration of escitalopram with MAO inhibitors.

Serotonin syndrome

Caution should be exercised when co-administration of escitalopram and serotonergic drugs, such as sumatriptan, other substances of the triptane group, tramadol and tryptophan. However, the development of serotonin syndrome in patients receiving both serotonergic drugs and SSRIs was extremely rare.The development of this syndrome may indicate such signs as agitation, tremor, myoclonus and hyperthermia. In this case, simultaneous reception of SSRIs and serotonergic drugs should be stopped immediately and symptomatic therapy should be started.

Use in children

The use of the drug in children is not recommended, since its effectiveness and safety in children are not fully understood.

Effect on the ability to drive transp. cf. and fur:

Although escitalopram does not affect psychomotor activity, during the period of treatment it is not recommended to drive or operate machinery.

Form release / dosage:

Tablets, film-coated, 10 mg and 20 mg.

Packaging:

For 14 tablets in a contour cell pack of Al / PVC / PE / PVDC.

2 contour packs with instructions for use in a cardboard pack.

Storage conditions:

Keep in dry the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000392

Date of registration:25.02.2011

Date of cancellation:2016-02-25

The owner of the registration certificate:NANOLEC, LTD. NANOLEC, LTD. Russia

Manufacturer: & nbsp

ABDI IBRAHIM ILAC SAN. VE TIC., A.S. Turkey

Representation: & nbspNANOLEC, LTD.NANOLEC, LTD.

Information update date: & nbsp04.10.2015

Illustrated instructions

Instructions

Miracitol (Miracetol)