Remeron®

Release form and composition

The dosage form of Remeron is film-coated tablets:

• 15 mg: biconvex, oval, in a yellow thin shell, with the embossed inscription “TZ/3” above and below the score on one side, and “ORGANON” on the opposite; the core is white with a uniform pressed structure (10 pieces in a blister, 1 or 3 blisters in a cardboard pack);
• 30 mg: biconvex, oval, in a red-brown thin shell, with the embossed inscription “TZ/5” above and below the score on one side, and “ORGANON” on the opposite; the core is white with a uniform pressed structure (10 pieces in a blister, 1 or 3 blisters in a cardboard pack);
• 45 mg: biconvex, oval, white, with embossed “TZ/7” on one side and “ORGANON” on the opposite side; the core is white with a uniform pressed structure (10 pieces in a blister, 1 or 3 blisters in a cardboard pack).

Composition of 1 tablet:

• Active ingredient: mirtazapine – 15, 30 or 45 mg;
• Additional components: lactose monohydrate, hyprolose, colloidal silicon dioxide, corn starch, magnesium stearate;
• Film coating: macrogol 8000, hypromellose, titanium dioxide, red iron oxide dye (for 30 mg), yellow iron oxide dye (for 15 and 30 mg).

Contraindications

• Glucose-galactose malabsorption, lactase deficiency, lactose intolerance;
• Hypersensitivity to the components of the drug.

It is not recommended to take the drug for children and adolescents under 18 years of age (due to the lack of data confirming the effectiveness and safety of its use).

The drug should be used with extreme caution (with regular medical supervision and dosage adjustment) for the following diseases and conditions:

• Liver or kidney failure;
• Heart disease (including recent myocardial infarction or angina, conduction disturbances);
• Organic brain damage, epilepsy (due to the threat of seizures);
• Arterial hypotension, conditions predisposing to the appearance of hypotension (including dehydration and hypovolemia);
• Cerebrovascular diseases (including a history of ischemic stroke);
• Mania, hypomania, dependence on medications that affect the central nervous system.

The drug is also used with caution in the presence of diabetes mellitus, urinary disorders (including prostatic hyperplasia), increased intraocular pressure, acute angle-closure glaucoma, and when combined with benzodiazepines.

It is not recommended to take Remeron during breastfeeding (due to the lack of information about the excretion of mirtazapine in breast milk).

During pregnancy, taking the drug is possible only if the expected benefit to the woman outweighs the potential threat to the fetus.

Consequences of drinking alcohol

If you mix antidepressants and alcohol, the effects can appear instantly, or they can occur with a delay of 1-2 hours. The outcome largely depends on concomitant factors, the body, the amount of drink consumed and the duration of therapy. The quality of alcohol and the availability of snacks also have a special influence.

The most likely consequences of the symbiosis of two substances:

• increased heart rate (up to 120 beats per minute);
• liver damage;
• hallucinations;
• development of depressive psychosis and sexual disorders;
• the risk of sudden changes in pressure increases;
• heart rhythm disturbance;
• insufficient or increased blood clotting.

Doctors and drug manufacturers warn buyers about possible complications of combining an antidepressant and alcohol. Such information is indicated in the instructions for use attached to the medication.

Directions for use and dosage

The tablets are taken orally, swallowed whole, without chewing, washed down with liquid if necessary.

Remeron is recommended to be used once a day (preferably in the evening, at the same time, before bedtime); it is also allowed to divide the daily dose into 2 doses - in the morning and evening (most of the dose should be taken at night).

At the beginning of the course, adults usually take 15-30 mg per day; the effective daily dose can vary from 15 to 45 mg.

When prescribing the drug to elderly patients, there is no need for dose adjustment. But dose increases required to achieve a safe and satisfactory response to therapy should be carried out under the supervision of a physician.

It should be taken into account that in case of renal or hepatic failure, the clearance of mirtazapine may be reduced.

Therapy with the drug is recommended, if possible, for 4-6 months (until the signs of the disease completely disappear), and then the course is gradually completed.

Remeron begins to have a therapeutic effect, usually 7-14 days after starting treatment. Using an adequate dosage allows you to get a positive response in 2-4 weeks. If the effect is insufficient, the dose can be increased to the maximum allowable - 45 mg per day.

If there are no positive changes in the patient's condition after another 2-4 weeks, therapy should be discontinued.

Remeron's analogues

Level 4 ATC code matches:
Pipofezin

Bethol

Incazan

Melitor

Azafen

Miaser

Velafax

Mirtazonal

Venlaxor

Venlafaxine

Lerivon

Mirtazapine

Cymbalta

Velaxin

Coaxil

Pyrazidol

Deprim

Gelarium Hypericum

Negrustin

Trittico

The closest analogues of the drug: Alventa, Velaxin, Venlaxor, Venlift, Gelarium Hypericum, Deprexor, Deprivit, Intriv, Coaxil, Medofaxin, Mianserin, Neuroplant, Pyrazidol, Trittico, Prefaxin, Negrustin, Valdoxan, Azafen, Normazidol, Venlafaxine, Cymbalta, Miaser, Melitor, Lerivon, Intriv, Deprim, Depresil, Wellbutrin, Brintellix .

Side effects

• Lymphatic system and blood: unknown frequency - eosinophilia, bone marrow depression (thrombocytopenia, agranulocytosis, granulocytopenia, aplastic anemia);
• Gastrointestinal tract: very often – dry mouth; often – vomiting, diarrhea, nausea; infrequently – decreased sensitivity of the oral mucosa; frequency not established - swelling of the oral mucosa;
• Nervous system: very often - drowsiness (appears during the first weeks of the course, reducing the dose, as a rule, does not help reduce the sedative effect), headache, sedation; often – tremor, dizziness, lethargy; uncommon – fainting, restless legs syndrome, paresthesia; rarely - myoclonus; very rarely - paresthesia of the oral mucosa, serotonin syndrome, convulsions (stroke);
• Psychiatry: often – insomnia, anxiety, confusion, unusual dreams; uncommon – psychomotor agitation (including hyperkinesia and akathisia), hallucinations, agitation, mania, nightmares; frequency not established - suicidal behavior, suicidal ideation;
• Skin and subcutaneous tissue: often – skin rash;
• Metabolism: very often – increased appetite;
• Endocrine system: frequency not established - impaired secretion of antidiuretic hormone;
• Connective and musculoskeletal tissue: often – myalgia, arthralgia, back pain;
• Vascular: often – orthostatic hypotension; uncommon – arterial hypotension;
• Liver and biliary tract: rarely - increased activity of serum transaminases;
• Other: infrequently - fatigue;
• Laboratory and instrumental data: very often - increase in body weight.

It should be taken into account that with depression there may be a number of symptoms associated with the disease. As a result, in some cases it is difficult to distinguish symptoms caused by the disease from side effects that arose during therapy.

According to available data, signs of an overdose of Remeron are usually mild. There have been reports of depression of the central nervous system, accompanied by prolonged sedation and disorientation in combination with a slight decrease or increase in blood pressure. But there is also a possibility of developing more severe consequences (including death) when taking doses significantly higher than the therapeutic dose, especially with overdoses of several drugs used simultaneously.

In such cases, symptomatic therapy is prescribed, aimed at maintaining the vital functions of the body, gastric lavage and taking activated charcoal.

Overdose

Available information regarding Remeron overdose suggests that symptoms are usually mild. There are reports of central nervous system depression, which was expressed in prolonged sedation and spatial disorientation in combination with a slight increase or decrease in blood pressure and tachycardia. However, taking a dose much higher than the therapeutic dose (especially in overdose caused by simultaneous use of several drugs) may carry a risk of more serious consequences, including death. In such cases, symptoms such as tachycardia of the “torsades de pointes” type and prolongation of the QT interval are observed.

In case of overdose, symptomatic therapy is prescribed to ensure the maintenance of vital body functions, and cardiac activity is regularly monitored using an ECG. It is also recommended to administer activated charcoal or perform gastric lavage.

special instructions

During therapy with Remeron, it is necessary to take into account that worsening of psychotic symptoms may occur when antidepressants are used to treat patients with schizophrenia or other psychotic disorders. When taking the drug, paranoid ideas may intensify, and the depressive phase of manic-depressive psychosis may turn into manic.

In patients under 24 years of age with depression and other mental disorders, taking antidepressants may increase the risk of suicidal behavior and suicidal thoughts. Before starting treatment, you should carefully weigh the possible risk of suicide and the expected benefit of the drug. During Remeron therapy, patients from this risk group should be monitored for timely detection of changes or behavioral disorders (including suicidal tendencies).

If symptoms of jaundice occur, the drug should be interrupted.

Despite the fact that the drug is not addictive, according to post-registration experience, abrupt interruption of long-term treatment may lead to withdrawal symptoms. Such reactions include nausea, anxiety, dizziness, headache, and agitation. All these effects are mild and self-limiting. It is recommended to discontinue Remeron therapy gradually.

During the treatment period you should avoid drinking alcohol.

When using the drug, in rare cases, the development of agranulocytosis and granulocytopenia is possible, observed in most cases after 4-6 weeks of the course and resolving after cessation of therapy. You should stop taking the drug and do a blood test if signs of a flu-like syndrome are detected (sore throat, fever, stomatitis, etc.).

When conducting monotherapy with mirtazapine, based on post-registration experience, the development of serotonin syndrome is extremely rare.

Since the drug may reduce concentration, it is recommended to refrain from driving vehicles and performing potentially hazardous activities during treatment.

Reviews about Remeron

Judging by reviews from doctors, the drug is most often prescribed for panic attacks and vegetative-vascular dystonia . The medicine is well tolerated, brings patients back to life, improves sleep and appetite. Sometimes, to eliminate side effects from taking it, additional medications are prescribed. It should be remembered that Remeron is a fairly serious medicine and should not be taken without the consultation and recommendations of the attending physician.

Reviews about Remeron on the forums:

“The pills are good for relieving depression. Depression is endogenous, it is useless to look for reasons. I can only save myself with medicine. Disadvantage: increased appetite”;

“My attacks - breathing problems, migraines, dizziness - Remeron relieved me perfectly. But it also has its own “side effects”: it’s impossible to sit still and it’s impossible to stop eating! I was constantly running around and couldn’t sleep. And she began to gain weight by leaps and bounds, even while limiting herself in food”;

“Switched to it from another medicine. The difference is amazing! It’s nice to feel like a real person again.”

Drug interactions

Possible interaction reactions of mirtazapine when combined with other drugs/substances:

• Benzodiazepines and other sedatives – their sedative properties are enhanced (caution should be exercised);
• Ethanol – its depressive effect on the central nervous system is aggravated;
• Selective serotonin reuptake inhibitors, venlafaxine and other serotonergic drugs - there is a possible risk of interaction, and as a consequence the development of serotonin syndrome (if such a combination is necessary, a dose change is required, and monitoring for signs of the onset of sustained serotonergic overstimulation);
• Warfarin - there was a small but statistically significant increase in MHO (international normalized ratio) when combined with mirtazapine at a dose of 30 mg;
• HIV protease inhibitors, potent inhibitors of the CYP3A4 isoenzyme, azole antifungals, nefazodone or erythromycin - the maximum plasma concentration and AUC of mirtazapine increases by 40-50% (should be combined with caution);
• Inducers of the CYP3A4 isoenzyme, phenytoin, carbamazepine - the clearance of mirtazapine increases, which leads to a decrease in its plasma concentration by 45-60% (dose adjustment required);
• Cimetidine - the bioavailability of mirtazapine increases by more than 50% (at the beginning of concomitant treatment with cimetidine, a reduction in the dose of mirtazapine may be required, and an increase upon discontinuation).

It is prohibited to take Remeron in combination with monoamine oxidase inhibitors (MAOIs), as well as for 14 days after their discontinuation.

Pharmacological properties

Remeron has established itself as an effective drug for the treatment of patients with depressive conditions, in which the clinical picture was dominated by symptoms such as weight loss, inability to experience feelings of joy and pleasure, sleep disturbances (mainly expressed in early awakenings), psychomotor retardation, anhedonia (loss of interest). ). The remedy is also applicable for conditions accompanied by mood swings during the day and suicidal thoughts. The antidepressant effect of Remeron usually begins to appear 1-2 weeks after the start of treatment.

Pharmacodynamics

Mirtazapine is an antagonist of presynaptic α2-adrenergic receptors in the central nervous system and activates serotonergic and central noradrenergic transmission of nerve impulses. In this case, the enhancement of serotonergic transmission occurs exclusively through serotonin 5-HT1 receptors, since mirtazapine blocks serotonin 5-HT2 and 5-HT3 receptors. It is assumed that both enantiomers of the active substance Remeron are characterized by antidepressant activity: in the case of the S(+)-enantiomer, this is realized by blocking serotonin 5-HT2- and α2-adrenergic receptors, and in the case of the R(-)-enantiomer, by blocking serotonin 5-HT3 -receptors. The sedative properties of mirtazapine are explained by its antagonistic activity towards histamine H1 receptors.

Mirtazapine is generally well tolerated. It has practically no anticholinergic activity, and in recommended doses it has a limited effect on the cardiovascular system (for example, orthostatic hypotension).

The use of Remeron in pediatric practice was studied in two randomized, double-blind, placebo-controlled studies. In them, children aged 7–18 years suffering from major depressive disorder (n = 259) received mirtazapine according to a flexible dosing regimen (doses of 15–45 mg) during the first 4 weeks, and over the next 4 weeks took the drug at fixed doses (15, 30 or 45 mg). Information obtained from the studies confirmed that there were no significant differences between mirtazapine and placebo. During the experiment, 48.8% of children receiving Remeron experienced significant (more than 7%) weight gain compared to the placebo group (this figure was 5.7%). Also, patients often experienced hypertriglyceridemia (in children taking mirtazapine, this figure was 2.9%, in those taking placebo - 0%) and urticaria (in children taking mirtazapine, this figure was 11.8%, in those taking placebo - 6). ,8%).

Pharmacokinetics

When Remeron is taken orally, mirtazapine is absorbed fairly quickly, and its bioavailability is 50%. The maximum concentration of the substance in the blood plasma is reached approximately 2 hours after administration. The degree of binding of mirtazapine to plasma proteins is 85%. On average, the half-life varies from 20 to 40 hours (in some cases up to 65 hours). In young patients, there is a tendency for the half-life to decrease. The equilibrium concentration of mirtazapine in the blood plasma is established 3-4 days after the start of treatment and subsequently remains unchanged.

When taking mirtazapine in therapeutic doses, its pharmacokinetic parameters linearly depend on the dose of the drug entering the body. Food intake does not affect the pharmacokinetics of Remeron.

Mirtazapine is actively involved in metabolic processes and is excreted through the kidneys and intestines over several days. The main pathways of metabolism of this substance in the body include oxidation and demethylation with further conjugation. The formation of the 8-hydroxy metabolite of mirtazapine occurs with the participation of cytochrome P450 isoenzymes (CYP1A2 and CYP2D6), and N-oxidized and N-demethylated metabolites are probably formed under the influence of the CYP3A4 isoenzyme. Demethylmirtazapine has pharmacological activity.

In patients with hepatic and/or renal impairment, the clearance of mirtazapine is reduced.