Active ingredient: Mirtazapine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Adrenergic alpha-Antagonists
• Antidepressive Agents, Tricyclic
• Histamine H1 Antagonists

Dosage Forms

• Tablet
• Tablet (orally disintegrating)

Brands / Synonyms

Mepirzepine; Mirtazapina [Inn-Spanish]; Mirtazapine; Mirtazapine [Usan:Ban:Inn]; Mirtazapinum [Inn-Latin]; Mirtazepine; Olsalazine; Remeron; Remeron Soltab

Indications

For the treatment of major depressive disorder.

Pharmacology

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.

Absorption

Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%.

Toxicity

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.

Contraindications

REMERONSolTab^Ò (mirtazapine) Orally Disintegrating Tablets are contraindicated in patients with a known hypersensitivity to mirtazapine.

Drug Interactions

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 REMERONSolTab^Ò (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 REMERONSolTab^Ò 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.

Alcohol

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 REMERON^Ò were shown to be additive with those produced by alcohol. Accordingly, patients should be advised to avoid alcohol while taking REMERONSolTab^Ò .

Diazepam

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 REMERON^Ò 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 REMERONSolTab^Ò .