MIRTAZONAL
Active material: Mirtazapine
When ATH: N06AX11
CCF: Antidepressant
ICD-10 codes (testimony): F31, F32, F33, F41.2
When CSF: 02.02.02
Manufacturer: ACTAVIS GROUP hf. (Iceland)
DOSAGE FORM, COMPOSITION AND PACKAGING
Pills, Film-coated chamois, Oval, lenticular, a mark on both sides and marked “I” – one.
| 1 tab. | |
| mirtazapine | 15 mg |
Excipients: lactose monohydrate, pregelatinized corn starch (starch 1500), silicon dioxide, Croscarmellose sodium, magnesium stearate, Opadry 03F22322 yellow (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000, dye iron oxide yellow, iron oxide red dye), Orange Opadry 03F23252 (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000, dye iron oxide yellow, iron oxide red dye), Opadry 03F28635 white (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000).
10 PC. – blisters (3) – packs cardboard.
Pills, Film-coated pink-brown, Oval, lenticular, a mark on both sides and marked “I” – one.
| 1 tab. | |
| mirtazapine | 30 mg |
Excipients: lactose monohydrate, pregelatinized corn starch (starch 1500), silicon dioxide, Croscarmellose sodium, magnesium stearate, Opadry 03F22322 yellow (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000, dye iron oxide yellow, iron oxide red dye), Orange Opadry 03F23252 (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000, dye iron oxide yellow, iron oxide red dye), Opadry 03F28635 white (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000).
10 PC. – blisters (3) – packs cardboard.
Pills, Film-coated white, Oval, lenticular, labeled “I” on one side.
| 1 tab. | |
| mirtazapine | 45 mg |
Excipients: lactose monohydrate, pregelatinized corn starch (starch 1500), silicon dioxide, Croscarmellose sodium, magnesium stearate, Opadry 03F22322 yellow (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000, dye iron oxide yellow, iron oxide red dye), Orange Opadry 03F23252 (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000, dye iron oxide yellow, iron oxide red dye), Opadry 03F28635 white (hypromellose 6cP, Titanium dioxide, makrogol / PEG 8000).
10 PC. – blisters (3) – packs cardboard.
Pharmacological action
Antidepressant chetyrehtsiklicheskoy structure with predominantly sedative effect. Α antagonist presinapticheskih2-adrenergic CNS, increases central noradrenergic and serotonergic neurotransmission. The amplification of the serotonergic transmission is realized only via the 5-HT1-receptors, since mirtazapine blocks serotonin 5-HT2 and 5-NT3-receptors. It is believed, Both enantiomers of mirtazapine have antidepressant activity, S (+) энантиомер блокирует a2-adrenoceptors and serotonin 5-HT2-receptors, a R (-) enantiomer blocking serotonin 5-HT3-receptors.
Sedative properties mirtazapine due to its antagonistic activity against histamine H1-receptors.
The most effective in the presence of depressive states in the clinical picture of symptoms, as the inability to experience pleasure and joy, loss of interest (angedonija), psychomotor retardation, sleep disorders (especially in the form of early awakenings) and weight loss, as well as other symptoms: suicidal thoughts and daily fluctuations in mood.
Mirtazapine is generally well tolerated. At therapeutic doses, practically no anticholinergic action and almost no effect on the cardiovascular system.
The antidepressant effect of the drug usually develops after 1-2 week of treatment.
Pharmacokinetics
Absorption
After taking the drug inside mirtazapine is rapidly absorbed. Cmax in plasma is approximately 2 no. Bioavailability is about 50%.
The recommended dose range pharmacokinetic mirtazapine have a linear dependence on the administered dose. Food intake has no effect on the pharmacokinetics of the drug.
Distribution
Plasma protein binding is about 85%.
Css plasma through krovidostigaetsya 3-4 day and no further changes.
Metabolism
Mirtazapine actively metaboliziruetsya. The main ways of its metabolism in the body are demethylation and oxidation followed by conjugation. The formation of 8-gidroksimetabolita mirtazapine involved isoenzymes CYP2D6 and CYP1A2 , while CYP3A4 expectation determines the formation of N-demethylated and N-oxidized metabolites. Demethyl-mirtazapine pharmacologically active and, apparently, pharmacokinetically similar to the parent compound.
Deduction
Average T1/2 It is between 20 h to 40 no (rarely up 65 no). Excreted in the urine and feces within a few days.
Pharmacokinetics in special clinical situations
A shorter T1/2 in young people.
The clearance of mirtazapine is reduced in patients with renal or hepatic insufficiency.
Testimony
- Depression.
Dosage regimen
The drug is taken orally, preferably 1 time / day in the evening before going to bed. Possible to use 2 times / day - morning and evening before going to bed.
Adult: effective daily dose is usually from 15 mg 45 mg; the initial dose – 15 mg or 30 mg. The higher dose should be taken at night.
Treatment should be possible to continue to complete absence of symptoms within 4-6 months. Thereafter, the drug can be gradually phased out.
The therapeutic effect usually appears after 1-2 weeks of treatment. Treatment of an adequate dose should result in a positive answer through 2-4 of the week. At insufficient response to treatment dose can be increased up to the maximum. In the absence of another therapeutic response through 2-4 week treatment should be discontinued.
To elderly patients the recommended dose of the same, as adult. In these patients in order to achieve a satisfactory and safe response to treatment dose increase should be carried out under the direct supervision of a physician.
In Patients with renal or hepatic insufficiency mirtazapine may slow excretion from the body.
The tablets should be taken with liquid and swallowed without chewing
Side effect
Patients with depression exhibit a number of symptoms, caused disease, so it is sometimes difficult to distinguish the symptoms, Related Disease, and symptoms, caused by the use of the drug.
From the central and peripheral nervous system: dizziness, headache, drowsiness (which can lead to impaired concentration), bowl occurs in the first days of weeks of treatment (it should be understood, dose reduction that normally does not reduce sedation, but it may affect the effectiveness of antidepressant); rarely - psychomotor retardation, alarm, hyperkinesia, myoclonus, gipokineziya, apathy, giperesteziya, tremor, convulsions, syndrome “Restless Legs”, feeling tired, craze, nightmares / vivid dreams.
From the hematopoietic system: rarely – inhibition of hematopoiesis (granulocytopenia, neutropenia, eozinofilija, agranulocytosis, aplasticheskaya anemia and thrombocytopenia).
From the digestive system: nausea, vomiting, constipation, abdominal pain, increase in liver transaminases, increased appetite, dry mouth.
On the part of the reproductive system: dysmenorrhoea.
From the urinary system: dizurija.
Metabolism: weight gain, edematous syndrome; rarely - thirst.
With the cardiovascular system: rarely - orthostatic hypotension, decrease in blood pressure.
On the part of the musculoskeletal system: rarely – backache, arthralgia, myalgia.
Other: rarely – hives, withdrawal.
Contraindications
- Up to 18 years (Safety and efficacy have not been established);
- Hypersensitivity to the drug.
FROM caution, under the supervision of a physician and a correction mode should be used on patients with epilepsy and organic brain damage (on background therapy with Mirtazonal in rare cases may develop convulsions), with hepatic or renal insufficiency, with heart disease (asequence, angina or recent myocardial infarction), patients with cerebrovascular disease (in t. no. with a history of ischemic), with hypotension and conditions, predisposing to hypotension (in t. no. with dehydration and hypovolemia), manias, hypomania, patients, Drug abuse, drug addiction.
FROM caution the drug should be used in patients with impaired micturition (in t. no. when prostatic hyperplasia), acute angle-closure glaucoma, and increased intraocular pressure, diabetic.
Pregnancy and lactation
The safety of the drug during pregnancy in humans has not been established, Therefore, the appointment is only possible in the case, when the expected benefit of therapy for the mother outweighs the potential risk to the fetus.
Use of the drug Mirtazonal lactation is not recommended due to lack of data on excretion of mirtazapine in breast milk in humans.
Cautions
When combined with other drugs should be borne in mind, that the worsening of psychotic symptoms can occur when use of antidepressants for the treatment of patients with schizophrenia or other psychotic disorders; may increase paranoid ideas; depressive phase of manic-depressive psychosis during treatment can transform into the manic phase; The risk of suicide, especially at the beginning of treatment, the patient should be given only a limited number of tablets.
Abrupt cessation of treatment after prolonged use can cause nausea, headache and malaise.
Elderly patients are usually more sensitive to drugs, particularly with regard to side effects. In clinical studies, the drug is not indicated Mirtazonal, that in these patients the side effects are more likely to, than in other age groups, but may be more pronounced.
If signs of jaundice, treatment should be discontinued.
Inhibition of bone marrow function, usually manifests itself in the form of granulocytopenia or agranulocytosis, rarely seen with Mirtazonala; It appears more likely after 4-6 weeks of treatment and is reversible after discontinuation of treatment. In case of an increase in body temperature, the appearance of pain in the throat, stomatitis, and other signs of influenza-like syndrome should stop treatment and blood tests. It should warn patients of the need to inform the doctor about the development of such symptoms.
Experience has shown post-marketing use, that serotonin syndrome occurs very rarely in patients, treated only drug Mirtazonal.
Precautions should be prescribed the drug simultaneously with benzodiazepines.
Patients with galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption, Mirtazapine should not be administered.
Patients are advised to avoid alcohol in the treatment of drug.
Use in Pediatrics
To children and adolescents under the age of 18 years with major depressive disorder in placebo-controlled studies safety and efficacy have not been established Mirtazonal, so the drug should not be used in these patients.
Effects on ability to drive vehicles and management mechanisms
Mirtazonal may reduce ability to concentrate attention and speed of psychomotor reactions. During treatment Mirtazonalom (Like other antidepressants) Patients should avoid driving and other potentially dangerous activities.
Overdose
Clinical safety Mirtazonala in overdose has not been investigated. Toxicity studies show no clinically significant cardiotoxicity during drug overdose.
Symptoms: CNS depression, accompanied by disorientation and prolonged sedation in conjunction with tachycardia and arterial hyper weak- or hypotension. However, there is a likelihood of more severe disorders of physiological functions, that can lead to death at doses, much higher than the therapeutic dose, especially when mixed overdose.
Treatment: recommended gastric lavage and administration of activated charcoal in the case of recent ingestion, shown symptomatic therapy.
Drug Interactions
Pharmacokinetic interactions
Mirtazapine is extensively metabolized with the participation of CYP2D6 and CYP3A4 isoenzymes, and to a lesser extent – with the participation of CYP1A2. The study of interaction in healthy volunteers showed, Chto paroxetine, inhibitor of CYP2D6, It has no effect on the pharmacokinetics of mirtazapine in equilibrium. Administering in combination with a potent inhibitor of CYP3A4 increases ketoconazole Cmax in plasma and AUC approximately mirtazapipa 40% and 50% respectively. Caution should be exercised when using mirtazapine combined with strong CYP3A4 inhibitors, HIV protease inhibitors, azole antifungal drugs, erythromycin or nefazodone.
Carbamazepine and phenytoin, индукторы CYP3A4, increased mirtazapine clearance about 2 times, resulting in 45-60% reduction of the concentration of mirtazapine in plasma.
When adding carbamazepine or another inducer of hepatic metabolism (eg, rifampicin) to mirtazapine therapy may require increased doses of mirtazapine. Upon termination of a similar drug treatment may be necessary to reduce the dose of mirtazapine.
In an application with cimetidine may increase the bioavailability of mirtazapine over 50%. With this combination at the beginning of treatment may require dose reduction of mirtazapine, the abolition of cimetidine - increasing the dose of mirtazapine.
In in vivo studies of drug interactions mirtazapine did not influence the pharmacokinetics of risperidone or paroxetine (substrate of CYP2D6), carbamazepine and phenytoin (a CYP3A4 substrate), amitriptyline and cimetidine.
There were no clinically significant effects or changes in pharmacokinetics in man for the treatment mirtazapine in combination with lithium.
Pharmacodynamic interactions
Mirtazapine should not be used in combination with MAO inhibitors or within 2 weeks after discontinuation of MAO inhibitor treatment.
Mirtazapine may potentiate the sedative properties of benzodiazepines and other sedatives. Caution should be exercised in the appointment of these medicines together with mirtazapine.
Mirtazapine may potentiate the inhibitory effect of ethanol on the CNS. Therefore, patients should be warned of the need to avoid alcohol .
In the case of other serotonergic drugs (eg, Selective serotonin reuptake inhibitors, venlafaxine) in sochetanii with mirtazapinom, there is a risk of interaction, which can lead to the development of serotonin syndrome. Based on post-marketing experience of the drug appeared, cider serotonin that occurs very rarely in patients, receiving mirtazapine in combination with a selective serotonin reuptake inhibitor venlafaxine or. If it is considered, that such a combination is necessary, it is necessary to carefully adjust the dose, and directly control the signs of the beginning of action to strengthen serotonin.
Mirtazapine doze 30 mg 1 time / day caused slight, but statistically significant increase MHO patients, treated with warfarin. We can not exclude a more pronounced effect at a higher dose of mirtazapine. It is recommended in the case of control MHO warfarin treatment in combination with mirtazapine.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.
