Calixta^® (Tablets) Instructions for Use

ATC Code

N06AX11 (Mirtazapine)

Active Substance

Mirtazapine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Antidepressant

Pharmacological Action

Antidepressant of tetracyclic structure. It enhances central noradrenergic and serotonergic transmission. It blocks serotonin 5-HT₂ and 5-HT₃ receptors, therefore the enhancement of serotonergic transmission is realized only through serotonin 5-HT₁ receptors.

Both spatial enantiomers participate in the manifestation of antidepressant activity: the S(+)-enantiomer blocks α₂-adrenoreceptors and serotonin 5-HT₂ receptors.

It moderately blocks histamine H₁ receptors and has a sedative effect.

It has little effect on α₁-adrenoreceptors and cholinoreceptors; in therapeutic doses, it does not have a significant effect on the cardiovascular system.

In clinical settings, an anxiolytic and hypnotic effect is also manifested, therefore Mirtazapine is most effective in anxious depressions of various origins.

Due to its moderate sedative effect, it does not actualize suicidal thoughts during treatment.

Pharmacokinetics

Mirtazapine is rapidly absorbed from the gastrointestinal tract after oral administration. The bioavailability is 50%. C_max in blood plasma is reached within 2 hours.

Steady-state concentration in blood plasma is established after 3-4 days of continuous use. Plasma protein binding is 85%.

It is actively metabolized in the liver by demethylation and oxidation followed by conjugation. Dimethyl-Mirtazapine is as pharmacologically active as the parent substance.

Mirtazapine is excreted by the kidneys and through the intestines. T_1/2 is 20-40 hours.

In renal and hepatic insufficiency, a decrease in the clearance of mirtazapine is possible.

Indications

Depressive states (including anhedonia, psychomotor retardation, insomnia, early awakening, weight loss, loss of interest in life, suicidal thoughts and mood lability).

ICD codes

Dosage Regimen

Tablets

When taken orally, the effective dose for adults is 15-45 mg/day, predominantly once a day before bedtime. The dose is gradually increased to 30-45 mg/day.

The antidepressant effect develops gradually, usually after 2-3 weeks from the start of treatment, but administration should be continued for another 4-6 months.

If no therapeutic effect is noted within 6-8 weeks of treatment, the treatment should be discontinued.

Discontinuation of mirtazapine should be carried out gradually.

Adverse Reactions

From the central and peripheral nervous system: drowsiness, lethargy, emotional lability, mental changes, agitation, anxiety, apathy, hallucinations, depersonalization, hostility, mania, epileptic seizures, dizziness, vertigo, hyperesthesia, convulsions, tremor, myoclonus, hyperkinesis, hypokinesia.

From the hematopoietic organs: inhibition of hematopoiesis – granulocytopenia, agranulocytosis, neutropenia, eosinophilia, aplastic anemia, thrombocytopenia.

From metabolism: slight increase in appetite and increase in body weight; in isolated cases – edema.

From the cardiovascular system: rarely – orthostatic hypotension.

From the digestive system: nausea, vomiting, constipation, increased appetite, increase in body weight, dry mouth, thirst, abdominal pain; in isolated cases – increased activity of liver transaminases.

From the reproductive system: decreased potency, dysmenorrhea.

Other: skin rashes, urticaria, flu-like syndrome, suffocation, edematous syndrome, myalgia, back pain, dysuria.

Contraindications

Renal and hepatic insufficiency, pregnancy, lactation, hypersensitivity to mirtazapine.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

Mirtazapine is not used in children due to the lack of data on its efficacy and safety in pediatric practice.

Special Precautions

Use with caution in patients with epilepsy and organic brain lesions, with impaired liver and/or kidney function, acute cardiovascular diseases, with arterial hypotension, with urination disorders due to benign prostatic hyperplasia, with angle-closure glaucoma, with diabetes mellitus.

In patients with schizophrenia, Mirtazapine may cause increased delusions and hallucinations. When treating the depressive phase of manic-depressive psychosis, this condition may turn into a manic phase.

Sudden discontinuation of mirtazapine after long-term treatment may cause nausea, headache, and malaise.

It should be borne in mind that if symptoms such as fever, sore throat, stomatitis appear during treatment, treatment should be discontinued and a clinical blood test should be performed.

If jaundice appears, mirtazapine should be discontinued.

It should not be used simultaneously with MAO inhibitors and for 2 weeks after their discontinuation.

Development of drug dependence and withdrawal syndrome is possible.

During treatment, patients should refrain from consuming alcohol.

Mirtazapine is not used in children due to the lack of data on its efficacy and safety in pediatric practice.

Effect on the ability to drive vehicles and operate machinery

Use with caution in patients whose activities require high concentration of attention and speed of psychomotor reactions.

Drug Interactions

With simultaneous use, Mirtazapine enhances the sedative effect of benzodiazepine derivatives.

A case of hypertensive crisis development with simultaneous use with clonidine has been described.

With simultaneous use with levodopa, a case of severe psychosis development has been described; with sertraline – a case of hypomania development.

With simultaneous use with ethanol, an increase in the inhibitory effect on the central nervous system of ethanol and ethanol-containing drugs is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.