Mirtazapine

7 DRUG INTERACTIONS Table 5 includes clinically important drug interactions with mirtazapine tablets [see Clinical Pharmacology (12.3) ]. Table 5: Clinically Important Drug Interactions with Mirtazapine Tablets Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of serotonergic drugs, including mirtazapine tablets, and MAOIs increases the risk of serotonin syndrome. Intervention Mirtazapine tablets are 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 tablets 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 tablets 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 tablets decreases the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3) ] . Intervention Increase the dose of mirtazapine tablets if needed with concomitant CYP3A inducer use. Conversely, a decrease in dosage of mirtazapine tablets 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 tablets may increase the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3) ] . Intervention Decrease the dose of mirtazapine tablets if needed with concomitant strong CYP3A inhibitor use. Conversely, an increase in dosage of mirtazapine tablets may be needed if the CYP3A inhibitor is discontinued [see Dosage and Administration (2.5) ] . Examples itraconazole, ritonavir, nefazodone Cimetidine Clinical Impact The concomitant use of cimetidine, a CYP1A2, CYP2D6, and CYP3A inhibitor, with mirtazapine tablets may increase the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3) ] . Intervention Decrease the dose of mirtazapine tablets if needed with concomitant cimetidine use. Conversely, an increase in dosage of mirtazapine tablets may be needed if cimetidine is discontinued [see Dosage and Administration (2.5) ] . Benzodiazepines and Alcohol Clinical Impact The concomitant use of benzodiazepines or alcohol with mirtazapine tablets increases the impairment of cognitive and motor skills produced by mirtazapine tablets alone. Intervention Avoid concomitant use of benzodiazepines and alcohol with mirtazapine tablets [see Warnings and Precautions (5.8) , Clinical Pharmacology (12.3) ] . Examples diazepam, alprazolam, alcohol Drugs that Prolong QTc Interval Clinical Impact The concomitant use of other drugs which prolong the QTc interval with mirtazapine tablets, increases the risk of QT prolongation and/or ventricular arrhythmias (e.g., Torsades de Pointes). Intervention Use caution when using mirtazapine tablets concomitantly with drugs that prolong the QTc interval [see Warnings and Precautions (5.5) , Clinical Pharmacology (12.3) ] . Warfarin Clinical Impact The concomitant use of warfarin with mirtazapine tablets may result in an increase in INR [see Clinical Pharmacology (12.3) ] . Intervention Monitor INR during concomitant use of warfarin with mirtazapine tablets. • Strong CYP3A Inducers: Dosage increase may be needed for mirtazapine tablets with concomitant use of strong CYP3A inducers. ( 2.5 , 7 ) • Strong CYP3A Inhibitors: Dosage decrease may be needed when mirtazapine tablets are coadministered with strong CYP3A inhibitors. ( 2.5 , 7 ) • Cimetidine: Dosage decrease may be needed when mirtazapine tablets are coadministered with cimetidine. ( 2.5 , 7 ) • Warfarin: Monitor INR during concomitant use. ( 7 )

"REMERON (mirtazapine) Tablets are indicated for the treatment of major depressive disorder," with efficacy established in placebo-controlled trials of outpatients meeting DSM criteria for a major depressive episode.

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 , 5.14 ) 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. Dose changes should not be made in intervals of less than 1 to 2 weeks to allow sufficient time for evaluation of response to a given dose [see Clinical Pharmacology (12.3) ] . 2.3 Screen for Bipolar Disorder Prior to Starting Mirtazapine Tablets Prior to initiating treatment with mirtazapine tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.9) ]. 2.4 Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of mirtazapine tablets. In addition, at least 14 days must elapse after stopping mirtazapine tablets before starting an MAOI antidepressant [see Contraindications (4) and Warnings and Precautions (5.3) ] . 2.5 Dosage Modifications Due to Drug Interactions Strong CYP3A Inducers An increase in dosage of mirtazapine tablets may be needed with concomitant strong CYP3A inducer (e.g., carbamazepine, phenytoin, rifampin) use. Conversely, a decrease in dosage of mirtazapine tablets may be needed if the CYP3A inducer is discontinued [see Drug Interactions (7) ]. Strong CYP3A Inhibitors A decrease in dosage of mirtazapine tablets may be needed with concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin). Conversely, an increase in dosage of mirtazapine tablets may be needed if the CYP3A4 inhibitor is discontinued [see Drug Interactions (7) ]. Cimetidine A decrease in dosage of mirtazapine tablets may be needed with concomitant use of cimetidine. Conversely, an increase in dosage of mirtazapine tablets may be needed if cimetidine is discontinued [see Drug Interactions (7) ]. 2.6 Discontinuation of Mirtazapine Tablets Treatment Adverse reactions may occur upon discontinuation or dose reduction of mirtazapine tablets [see Warnings and Precautions (5.14) ] . Gradually reduce the dosage of mirtazapine tablets rather than stopping abruptly whenever possible.

The most frequently reported adverse reactions include "somnolence" (about 54%), "increased appetite" (about 17%), "weight gain" (about 12%), and "dizziness" (about 7%), along with dry mouth and constipation. Somnolence and appetite/weight changes are notably prominent compared with many other antidepressants.