Overview
11 DESCRIPTION Mirtazapine tablets, USP contain mirtazapine USP. Mirtazapine has a tetracyclic chemical structure and belongs to the piperazino-azepine group of compounds. It is designated 1,2,3,4,10,14b-hexahydro-2-methylpyrazino [2,1-a] pyrido [2,3-c][2] benzazepine and has the molecular formula of C 17 H 19 N 3 . Its molecular weight is 265.35.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of mirtazapine for the treatment of major depressive disorder, is unclear. However, its efficacy could be mediated through its activity as an antagonist at central presynaptic α 2 -adrenergic inhibitory autoreceptors and heteroreceptors and enhancing central noradrenergic and serotonergic activity. 12.2 Pharmacodynamics In preclinical studies, mirtazapine acts as an antagonist at α 2 -adrenergic inhibitory autoreceptors and heteroreceptors and as an antagonist at serotonin 5-HT 2 and 5-HT 3 receptors. Mirtazapine has no significant affinity for the 5-HT 1A and 5-HT 1B receptors. Mirtazapine also acts as an antagonist of histamine (H 1 ) receptors, peripheral α 1 -adrenergic receptors, and muscarinic receptors.
Indications
- 1 INDICATIONS AND USAGE Mirtazapine tablets are indicated for the treatment of major depressive disorder (MDD) in adults [see Clinical Studies (14) ]. Mirtazapine tablets are indicated for the treatment of major depressive disorder (MDD) in adults. ( 1 )
Common Doses
- 15 mg
- 45 mg
Dosage
2 DOSAGE AND ADMINISTRATION • Starting dose: 15 mg once daily; may increase up to maximum recommended dose of 45 mg once daily. ( 2.1 ) • Administer orally once daily, preferably in the evening prior to sleep. ( 2.1 ) • Reduce dose gradually when discontinuing mirtazapine tablets. ( 2.6 , 5.13 ) 2.1 Recommended Dosage The recommended starting dose of mirtazapine tablets is 15 mg once daily, administered orally, preferably in the evening prior to sleep. If patients do not have an adequate response to the initial 15 mg dose, increase the dose up to a maximum of 45 mg per day.
Black Box Warning
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1) ] . Mirtazapine tablets are not approved for use in pediatric patients [see Use in Specific Populations (8.4) ]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning.
Contraindications
- 4 CONTRAINDICATIONS Mirtazapine tablets are contraindicated in patients: • Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.3) , Drug Interactions (7) ]. • With a known hypersensitivity to mirtazapine or to any of the excipients in mirtazapine tablets. Severe skin reactions, including Stevens-Johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have been reported following the use of mirtazapine tablets [see Adverse...
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are described in more detail in other sections of the prescribing information: • Hypersensitivity [see Contraindications (4) ] • Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.1) ] • Agranulocytosis [see Warnings and Precautions (5.2) ] • Serotonin Syndrome [see Contraindications (4) , Warnings and Precautions (5.3) , Drug Interactions (7) ] • Angle-Closure Glaucoma [see Warnings and Precautions (5.4) ] • QT Prolongation and Torsades de Pointes [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Table 5 includes clinically important drug interactions with mirtazapine [see Clinical Pharmacology (12.3) ]. Table 5: Clinically Important Drug Interactions with Mirtazapine Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of serotonergic drugs, including mirtazapine, and MAOIs increases the risk of serotonin syndrome. Intervention Mirtazapine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.4) , Contraindications (4) , Warnings and Precautions (5.3) ].