Drug Interactions

Contraindications for co-administration (Do not co-administer with the following.)

Drugs	Signs, symptoms, and Treatment	Mechanism and Risk factors
MAO inhibitors Selegiline hydrochloride Rasagiline mesilate	Serious adverse reactions including hypertensive crisis and serotonin syndrome may occur. At least 14 days should elapse between discontinuation of this drug and initiation of the drugs in the left column. In addition, at least 14 days should elapse between discontinuation of the drugs in the left column and initiation of this drug.	The effect of this drug to inhibit MAO-B may induce an additive effect.
Pethidine hydrochloride-containing products Tramadol hydrochloride-containing Products Tapentadol hydrochloride	Serious adverse reactions including serotonin syndrome may occur. At least 14 days should elapse between discontinuation of this drug and initiation of the drugs in the left column. In addition, at least 2 to 3 days should elapse between discontinuation of tramadol hydrochloride-containing products and initiation of this drug.	The mechanism is not known.
Tricyclic antidepressants Amitriptyline hydrochloride Amoxapine Imipramine hydrochloride Clomipramine hydrochloride Dosulepin hydrochloride Trimipramine maleate Nortriptyline hydrochloride Lofepramine hydrochloride	Co-administration with other MAO-B inhibitors was associated with adverse reactions including hypertension, syncope, asystole, sweating, epilepsy, altered motor/mental disorder, and rigidity, and the reports of death. At least 14 days should elapse between discontinuation of this drug and initiation of the drugs in the left column. In addition, at least 2 to 3 days should elapse between discontinuation of the drugs in the left column and initiation of this drug.	Additive or synergistic effects may occur, although the mechanism is not known.
Tetracyclic antidepressants Maprotiline hydrochloride Mianserin hydrochloride Setiptiline maleate
Selective serotonin reuptake inhibitors Fluvoxamine maleate Paroxetine hydrochloride hydrate Sertraline hydrochloride Escitalopram oxalate	Serious adverse reactions including serotonin syndrome may occur. At least 14 days should elapse between discontinuation of this drug and initiation of the drugs in the left column. In addition, between discontinuation of the drugs in the left column and initiation of this drug, at least 7 days should elapse for fluvoxamine maleate, and at least 14 days should elapse for paroxetine hydrochloride hydrate, sertraline hydrochloride, and escitalopram oxalate.	The effect of these drugs to inhibit serotonin reuptake may increase brain serotonin concentration.
Serotonin–noradrenaline reuptake inhibitors Milnacipran hydrochloride Duloxetine hydrochloride Venlafaxine hydrochloride	Serious adverse reactions including serotonin syndrome may occur. At least 14 days should elapse between discontinuation of this drug and initiation of the drugs in the left column. In addition, between discontinuation of the drugs in the left column and initiation of this drug, at least 2 to 3 days should elapse for milnacipran hydrochloride, at least 5 days should elapse for duloxetine hydrochloride, and at least 7 days should elapse for venlafaxine hydrochloride.	The degradation of monoamine neurotransmitters may be suppressed, and the total amount of monoamine in the brain may increase.
Selective noradrenaline reuptake inhibitors Atomoxetine hydrochloride	Serious adverse reactions including serotonin syndrome may occur. At least 14 days should elapse between discontinuation of this drug and initiation of the drugs in the left column. In addition, at least 14 days should elapse between discontinuation of the drugs in the left column and initiation of this drug.
Noradrenergic and serotonergic antidepressant Mirtazapine	Serious adverse reactions including serotonin syndrome may occur. At least 14 days should elapse between discontinuation of this drug and initiation of the drugs in the left column. In addition, at least 14 days should elapse between discontinuation of the drugs in the left column and initiation of this drug.	The neurotransmission of noradrenaline and serotonin in the brain may be enhanced, and the total amount of monoamine in the brain may increase.
Central nervous system stimulants Methylphenidate hydrochloride Lisdexamfetamine mesilate	Serious adverse reactions including hypertensive crisis may occur. At least 14 days should elapse between discontinuation of this drug and initiation of the drugs in the left column.	The total amount of monoamine in the brain may increase.

Precautions for Co-administration (This drug should be administered with caution when co-administered with the following.)

*Drugs*	*Signs, symptoms, and Treatment*	*Mechanism and* *Risk factors*
Trazodone hydrochloride	Administration of this drug immediately after discontinuation of trazodone hydrochloride or concomitantly with trazodone hydrochloride may increase brain serotonin concentration.	The effect of this drug to inhibit serotonin reuptake may increase brain serotonin concentration.
Reserpine derivative Reserpine	The effect of this drug may be reduced.	Brain dopamine is reduced.
Phenothiazines Chlorpromazine Butyrophenones Haloperidol Sulpiride Metoclopramide	The effect of this drug may be reduced.	The dopamine receptors in the brain are blocked.
Dextromethorphan hydrobromide hydrate	Serotonin syndrome may occur.	The effect of dextromethorphan hydrobromide hydrate to increase brain serotonin concentration may further increase brain serotonin concentration
Linezolid	Increased blood pressure, etc. including hypertensive crisis may occur.	Coadministration with linezolid, which has a nonselective, reversible MAO inhibitory effect, may induce an additive effect.
Sympathomimetic agents: Ephedrine hydrochloride Methylephedrine hydrochloride Pseudoephedrine hydrochloride-containing drugs Phenylpropanolamine-containing drugs	Increased blood pressure including hypertensive crisis may occur.	The sympathomimetic effect of these drugs may be enhanced if the selectivity for MAO-B is lowered.