Brands, Medical Use, Clinical Data
- Adrenergic alpha-Antagonists
- Antidepressive Agents, Tricyclic
- Histamine H1 Antagonists
- Tablet (orally disintegrating)
Brands / Synonyms
Mepirzepine; Mirtazapina [Inn-Spanish]; Mirtazapine; Mirtazapine [Usan:Ban:Inn]; Mirtazapinum [Inn-Latin]; Mirtazepine; Olsalazine; Remeron; Remeron Soltab
For the treatment of major depressive disorder.
Mirtazapine, an antidepressant of the piperazinoazepine class, is a tetracyclic compound with an anxiolytic effect. Mirtazapine has fewer ADRs than tricyclic antidepressants and is better tolerated. Selective blockade of specific serotonin receptors by mirtazapine likey minimizes side effects typical of other antidepressants.
Mechanism of Action
Mirtazapine acts as an antagonist at central pre-synaptic alpha(2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in NE release. Blockade of heteroreceptors, alpha(2)-receptors contained in serotenergic neurons, enhances the release of 5-HT, increasing the interactions between 5-HT and 5-HT1 receptors and contributing to the anxiolytic effects of mirtazapine. Mirtazapine also acts as a weak antagonist at 5-HT1 receptors and as a potent antagonist at 5-HT2 (particularly subtypes 2A and 2C) and 5-HT3 receptors. Blockade of these receptors may explain the lower incidence of adverse effects such as anxiety, insomnia, and nausea. Mirtazapine also exhibits significant antagonism at H1-receptors, resulting in sedation. Mirtazapine has no effects on the reuptake of either NE or 5-HT and has only minimal activity at dopaminergic and muscarinic receptors.
Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%.
Symptoms of overdose include disorientation, drowsiness, impaired memory, and tachycardia. LD50=mg/kg (orally in rat).
Biotrnasformation / Drug Metabolism
Mirtazapine is extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. Cytochrome P450 2D6 and cytochrome P450 1A2 are involved in formation of the 8-hydroxy metabolite of mirtazapine, and cytochrome P450 3A4 is responsible for the formation of the N-desmethyl and N-oxide metabolites. Several metabolites possess pharmacological activity, but plasma levels are very low.
REMERONSolTabÒ (mirtazapine) Orally Disintegrating Tablets are
contraindicated in patients with a known hypersensitivity to mirtazapine.
As with other drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic,
pharmacokinetic inhibition or enhancement, etc.) is a possibility.
Drugs Affecting Hepatic Metabolism
The metabolism and pharmacokinetics of REMERONSolTabÒ (mirtazapine)
Orally Disintegrating Tablets may be affected by the induction or inhibition of drug-metab-olizing enzymes.
Drugs that are Metabolized by and/or Inhibit Cytochrome P450 Enzymes
Many drugs are metabolized by and/or inhibit various cytochrome P450 enzymes, e.g., 2D6, 1A2, 3A4, etc. In vitro
studies have shown that mirtazapine is a substrate for several of these enzymes, including 2D6, 1A2, and 3A4. While
in vitro studies have shown that mirtazapine is not a potent inhibitor of any of these enzymes, an indication that
mirtazapine is not likely to have a clinically significant inhibitory effect on the metabolism of other drugs that
are substrates for these cytochrome P450 enzymes, the concomitant use of REMERONSolTabÒ with most other drugs metabolized by these enzymes has not been formally studied.
Consequently, it is not possible to make any definitive statements about the risks of coadministration of
REMERONSolTab® with such drugs.
Concomitant administration of alcohol (equivalent to 60 g) had a minimal effect on plasma levels of mirtazapine
(15 mg) in 6 healthy male subjects. However, the impairment of cognitive and motor skills produced by
REMERONÒ were shown to be additive with those produced by alcohol.
Accordingly, patients should be advised to avoid alcohol while taking REMERONSolTabÒ .
Concomitant administration of diazepam (15 mg) had a minimal effect on plasma levels of mirtazapine (15 mg) in 12
healthy subjects. However, the impairment of motor skills produced by REMERONÒ has been shown to be additive with those caused by diazepam. Accordingly, patients
should be advised to avoid diazepam and other similar drugs while taking REMERONSolTabÒ .