Mirtazapine (3 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, ORALLY DISINTEGRATING, TABLET.
Routes of administration: ORAL.
Brand Names
- MIRTAZAPINE
- REMERON
- REMERON SOLTAB
Boxed Warning
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) ].
Indications and Usage
Mirtazapine tablets are indicated for the treatment of major depressive disorder (MDD) in adults [see Clinical Studies (14)].
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 drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have been reported following the use of mirtazapine tablets [see Warnings and Precautions (5.6), Adverse Reactions (6.2)].
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 (5.5) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.6) ] Increased Appetite and Weight Gain [see Warnings and Precautions (5.7) ] Somnolence [see Warnings and Precautions (5.8) ] Activation of Mania or Hypomania [see Warnings and Precautions (5.9) ] Seizures [see Warnings and Precautions (5.10) ] Elevated Cholesterol and Triglycerides [see Warnings and Precautions (5.11) ] Hyponatremia [see Warnings and Precautions (5.12) ] Transaminase Elevations [see Warnings and Precautions (5.13) ] Discontinuation Syndrome [see Warnings and Precautions (5.14) ] Use in Patients with Concomitant Illness [see Warnings and Precautions (5.15) ]
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)]. Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with mirtazapine increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of mirtazapine and/or concomitant serotonergic drugs [see Warnings and Precautions (5.3)]. Examples SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, amphetamines, St. John’s Wort, tramadol, tryptophan, buspirone Strong CYP3A Inducers Clinical Impact The concomitant use of strong CYP3A inducers with mirtazapine decreases the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3)]. Intervention Increase the dose of mirtazapine if needed with concomitant CYP3A inducer use. Conversely, a decrease in dosage of mirtazapine may be needed if the CYP3A inducer is discontinued [see Dosage and Administration (2.5)]. Examples phenytoin, carbamazepine, rifampin Strong CYP3A Inhibitors Clinical Impact The concomitant use of strong CYP3A inhibitors with mirtazapine may increase the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3)]. Intervention Decrease the dose of mirtazapine if needed with concomitant strong CYP3A inhibitor use. Conversely, a
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.
Overdosage
Human Experience In premarketing clinical studies, there were reports of mirtazapine overdose alone or in combination with other pharmacological agents. Signs and symptoms reported in association with overdose included disorientation, drowsiness, impaired memory, and tachycardia. Based on postmarketing reports, serious outcomes (including fatalities) may occur at dosages higher than the recommended doses, especially with mixed overdoses. In these cases, QT prolongation and Torsades de Pointes have also been reported [see Warnings and Precautions (5.5), Adverse Reactions (6.2), and Drug Interactions (7)]. Overdose Management No specific antidotes for mirtazapine are known. Contact Poison Control (1-800-222-1222) for the latest recommendations.