Pharmacodynamics The active substance of the drug Mirtazapine Sandoz - mirtazapine - is an active central presynaptic antagonist of α2 receptors, which increases noradrenergic and serotonergic transmission to the central nervous system. Increased serotonergic transmission occurs exclusively through 5-HT1 receptors, since mirtazapine blocks 5-HT2 and 5-HT3 receptors. mirtazapine cheap online Both enantiomers of mirtazapine are involved in this effect. S (+) - enantiomer blocks α2 and 5-HT2 receptors, and R (-) - enantiomer blocks 5-HT3 receptors. In addition, mirtazapine blocks H1 receptors, which determines its sedative properties. In therapeutic doses, practically does not show anticholinergic activity and does not affect the cardiovascular system.
Pharmacokinetics After oral administration, mirtazapine is rapidly and well absorbed (bioavailability is about 50%), reaching Cmax in blood plasma after about 2 hours. Almost 85% of mirtazapine binds to plasma proteins. Average T½ - 20–40 hours; cases were recorded when T½ was 65 hours; shorter T½ is usually observed in young patients. A longer T½ allows you to take the drug 1 time per day. A stable concentration is achieved after 3-4 days, after which the accumulation passes. Within the recommended dose, the pharmacokinetic parameters of mirtazapine are linearly dependent on the dose taken. Eating does not affect the pharmacokinetics of mirtazapine.
Mirtazapine is actively metabolized and excreted in the urine and feces for several days. The main ways of biotransformation are demethylation and oxidation with further conjugation. In vitro data (liver microsomes) indicate that the CYP 2D6 and CYP 1A2 enzymes of cytochrome P450 are involved in the formation of mirtazapine 8-hydroxymetabolite, while CYP 3A4 forms N-dimethyl and N-oxide metabolites. N-dimethyl metabolite is pharmacologically active and exhibits a similar pharmacological effect as the starting substance.
Mirtazapine clearance may decrease in renal or hepatic impairment.
Interaction with other drugs and other types of interactions
Mirtazapine should not be taken concomitantly with MAO inhibitors or within 2 weeks after the end of therapy. After completion of treatment with mirtazapine, approximately 2 weeks should pass before patients can use MAO inhibitors..
In addition, the simultaneous administration of mirtazapine with selective serotonin reuptake inhibitors and other serotonergic active substances (L-tryptophan, triptans, tramadol, linezolid, venlafaxine, lithium, and preparations containing St. John's wort (Hypericum perforatum) can lead to effects Serotonin.With the combined use of these active substances with mirtazapine, it is recommended to be careful and under close medical supervision.
Mirtazapine may enhance the sedative properties of benzodiazepines and other sedative drugs (including most antipsychotics, H 1 receptor antagonists, opioids). Caution should be exercised when prescribing these medicines with mirtazapine..
Mirtazapine may enhance the depressive effect of alcohol on the central nervous system, so patients should refrain from drinking alcohol during treatment with the drug.
Mirtazapine at a dose of 30 mg once a day caused a small, but statistically significant increase in PIM (International Normalized Index, INR) in patients treated with warfarin.
It is recommended to monitor PIM in case of concomitant use of warfarin with mirtazapine due to the possibility of its increase.
The risk of lengthening the QT interval and / or ventricular arrhythmias (e.g., torsade de pointes) may increase with the simultaneous use of drugs that extend the QT interval (e.g., some antipsychotics and antibiotics).
Carbamazepine and phenytoin, CYP3A4 inducers increase the clearance of mirtazapine by approximately 2 times and, as a result, the average concentration of mirtazapine in blood plasma decreases by 60% and 45%, respectively. When carbamazepine or any other inducer of hepatic metabolism (eg, rifampicin) is added to mirtazapine therapy, the dose of the latter should be increased. If treatment with such a drug is discontinued, it may be necessary to reduce the dose of mirtazapine..
The simultaneous use of the potent inhibitor of CYP3A4 ketoconazole increased peak plasma levels and AUC (the area under the concentration / time curve) of mirtazapine by approximately 40% and
When using cimetidine (a weak inhibitor of CYP1A2, CYP2D6 and CYP3A4) with mirtazapine, the average plasma concentrations of mirtazapine can increase by more than 50%. Precautions should be taken and the dose should be reduced when combined with mirtazapine and potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungal agents, erythromycin, cimetidine or nefazodone.
No clinically significant pharmacokinetic interaction was found with the simultaneous use of mirtazapine with paroxetine, amitriptyline, risperidone or lithium.
Elena, 45 years old:
The only thing, getting up in the morning in the first weeks was hard, for about forty minutes I came to my senses, but as I got used to it, it passed.
In general, I am satisfied, the medicine is not cheap, it takes a long time to be treated, but I got rid of my problems.
Ivan, 25 years old:
Price, quality level. The main thing is that the depression has passed, I live like a person, I am happy and upset, but in moderation - without getting stuck.
Ksenia, 45 years old:
Soon, I completely forgot about my nervous disorders. After the drug was canceled, there were a couple of unpleasant days (nausea, weakness), then everything worked out. I am a teetotaler with a normal psyche, with a loving husband and a nice four-year-old daughter!
Manufacturer's location and address of the place of business
Otto-on-Gürike alle 1, 39179, Barleben, Germany.
- The use of the substance Mirtazapine
- Application restrictions
- Pregnancy and lactation
- Side effects of the substance Mirtazapine