Index of drugs

Treatment of major depressive episodes.

1 tabl powl. contains 30 mg or 45 mg of mirtazapine hemihydrate; Table. powl. contain lactose. 1 tabl orodispersible (Q-Tab) contains 15 mg, 30 mg or 45 mg mirtazapine; Table. Q-Tab contains lactose, sorbitol and aspartame.

Antidepressant. Mirtazapine is a centrally active presynaptic α-receptor antagonist₂, which increases noradrenergic and serotoninergic neurotransmission in o.u.n. Enhancement of serotoninergic neurotransmission is mediated in particular by 5-HT1 receptors, because 5-HT2 and 5-HT3 receptors are blocked by mirtazapine. Both mirtazapine enantiomers have antidepressant activity, the S (+) enantiomer by blocking the α-receptors₂ and 5-HT2, and the R (-) enantiomer by blocking 5-HT3 receptors. The sedative properties of mirtazapine result from its action as an antagonist of the histamine H1 receptor. Mirtazapine has virtually no anticholinergic activity, in therapeutic doses practically has no effect on the cardiovascular system. After oral administration, mirtazapine is well and rapidly absorbed (bioavailability of about 50%), reaching a maximum plasma concentration after about 2 hours. The degree of binding to plasma proteins is about 85%. T_0,5 in the elimination phase is 20-40 h; occasional longer half-lives were observed - up to 65 h, and also shorter - in young people. Steady state is achieved after 3-4 days, after which there is no further accumulation of the drug. Mirtazapine undergoes rapid transformation and is excreted in urine and faeces within a few days. The main metabolic pathways are demethylation and oxidation followed by conjugation. CYP2D6 and CYP1A2 (8-hydroxymetabolite) and CYP3A4 (N-demethyl and N-oxide metabolites) are involved in the metabolism of the drug. The demethyl metabolite is pharmacologically active and appears to have the same pharmacokinetic profile as the parent compound.

Hypersensitivity to mirtazapine or to any of the excipients. Concurrent use with MAO inhibitors.

The preparation should not be used to treat children and adolescents under 18 years of age. Suicide related behaviors (suicide attempts and suicidal thoughts) and hostility (mainly aggression, rebel behavior and anger) have been more frequently observed in clinical trials among children and adolescents treated with antidepressants than those treated with placebo. If, however, based on clinical needs, a decision to treat has been made, the patient should be carefully monitored for signs of suicide. In addition, the lack of long-term data on the safety of use in children and adolescents regarding growth, maturation and cognitive and behavioral development. Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. The patient should be closely monitored until improvement occurs and in the early stages of recovery (increased risk of suicide). Patients with a history of suicide-related events or patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment are considered to be at increased risk of suicidal thoughts or suicide attempts and should be closely monitored during treatment, particularly in patients below 25 years of age. Due to the possibility of committing suicide, especially at the beginning of treatment, the patient should receive only a limited number of tablets of the preparation. Due to the risk of bone marrow suppression (usually with granulocytopenia or agranulocytosis), the doctor should be alert to symptoms such as fever, sore throat, stomatitis or other signs of infection; if such symptoms occur, stop treatment and perform a blood test. Treatment should be discontinued if jaundice occurs. Careful dosing, as well as systematic and close monitoring are necessary for patients with: epilepsy or organic cerebral syndrome (the drug should be introduced with caution in patients with a history of epileptic seizures; treatment should be discontinued in any patient who develops seizures or when he or she increase the frequency of epileptic seizures); impaired liver function; impaired renal function; heart disease such as conduction disorders,angina or recent myocardial infarction (regular precautions should be taken and the doses of concomitant medications should be carefully selected); low blood pressure; diabetes (antidepressants can change glycemic control - a change in the dose of insulin and / or oral hypoglycemic agents may be required, constant supervision of the doctor is recommended). The use of antidepressants in patients with schizophrenia or other mental disorders may worsen their condition; it may also come from the intensification of paranoid thoughts. During the treatment of the depressive phase of bipolar disorder, the transition to the manic phase may occur; patients with mania / hypomania history should be carefully observed. Discontinue mirtazapine in any patient entering the manic phase. Caution should be exercised in patients with impaired urination, such as in the case of prostatic hyperplasia, and in patients with acute narrow-angle glaucoma and elevated intraocular pressure. In patients who present with symptoms of akathisia, increasing the dose may be harmful. Due to the risk of hyponatremia caused probably by inappropriate secretion of antidiuretic hormone (SIADH), caution should be used in at-risk patients such as elderly patients or those taking medicines that are known to induce hyponatremia. Due to the risk of serotonin syndrome, caution should be exercised and clinical monitoring should be used with the use of mirtazapine and selective serotonin reuptake inhibitors and other serotonergic agents. If symptoms of the serotonin syndrome occur, treatment with mirtazapine should be discontinued and symptomatic supportive care should be given. Elderly patients are often more sensitive to the side effects of antidepressants. The product contains lactose - should not be used in patients with rare congenital problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. In addition, tabl. orally disintegrating (Q-Tab) contains sorbitol - should not be used in patients with rare congenital problems of fructose intolerance, and aspartame (source of phenylalanine), which may be harmful for patients with phenylketonuria.

Limited data on the use of mirtazapine in pregnant women do not show an increased risk of congenital malformations. Caution should be exercised when prescribing mirtazapine to pregnant women. If the preparation is taken during pregnancy or shortly before delivery, it is recommended to observe the newborn because of the possibility of withdrawal symptoms. The results of epidemiological studies indicate that the use of serotonin reuptake inhibitors (SSRIs) in pregnant women, especially in the third trimester, may increase the risk of persistent pulmonary hypertension syndrome (PPHN). Although no studies have been conducted regarding PPHN with mirtazapine treatment, this risk can not be excluded given the associated mechanism of action (increased serotonin levels). Mirtazapine is secreted only in very small amounts with milk. The decision on whether to continue or stop breastfeeding or to continue or stop treatment with the product should be made after considering the benefits of breastfeeding for the child and the benefits of therapy for the woman.

Very common: drowsiness, sedation, headache, dry mouth, weight gain, increased appetite. Common: lethargy, dizziness, tremor, nausea, diarrhea, vomiting, rash, pain in the joints, muscles, back, orthostatic hypotension, peripheral edema, fatigue, unusual dreams, confusion, anxiety, insomnia. Uncommon: paresthesia, restless legs syndrome, syncope, hypoaesthesia, hypotension, nightmares, mania, agitation, hallucinations, psychomotor restlessness (including akathisia, hyperkinesia). Rarely: muscle clonic convulsions, transaminase elevations, aggressive behavior. Not known: bone marrow depression (granulocytopenia, agranulocytosis, plastic anemia, thrombocytopenia), eosinophilia, convulsions (seizures), serotonin syndrome, oral paresthesia, dysarthria, oral edema, increased salivation, Stevens-Johnson syndrome, bladder dermatitis , erythema multiforme, toxic-epithelial necrosis, hyponatraemia, somnambulism, suicidal thoughts, suicidal behavior, inappropriate secretion of antidiuretic hormone. In laboratory evaluation of clinical trials transient elevations of transaminases and GGT were observed (although associated adverse events were not statistically significantly more frequently reported than in the placebo group).The following adverse events were frequently observed in clinical trials in children: weight gain, urticaria and hypertriglyceridaemia.
Abrupt discontinuation may cause withdrawal symptoms. Most of them are mild and self-limiting. Dizziness, agitation, anxiety, headaches and nausea were the most frequently reported.

Orally. Adults: effective daily dose is usually 15-45 mg; treatment should start with an initial dose of 15 mg or 30 mg. The antidepressant effect usually manifests after 1-2 weeks of use. Treatment with the right dose should give a positive response within 2-4 weeks. In the case of insufficient response, the dose may be increased to the maximum dose. If there is no adequate clinical response within the Next 2-4 weeks, treatment should be discontinued. In patients with depression, treatment should continue until complete resolution of symptoms, which usually lasts for at least 6 months. Elderly patients do not need to adjust the dose, but the dose should be increased under strict control to obtain a satisfactory and safe clinical response. . In patients with moderate to severe renal impairment (creatinine clearance <40 ml / min) and in patients with hepatic impairment, clearance of mirtazapine may be reduced - this should be taken into account when prescribing to such patients, especially those with severe hepatic this problem has not been studied. The preparation can be administered in a single daily dose, preferably in the evening, before going to bed. The drug can also be administered in 2 divided doses (one dose in the morning and the other, a larger dose in the evening). Coated tablets should be swallowed whole with liquid; you should not chew them. Q-Tab tablets rapidly disintegrate in the mouth and can be swallowed without being taken with water.