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Monoamine Oxidase Inhibitors

With other drugs that affect brain monoamine concentrations, there have been reports of serious, sometimes fatal reactions (including rigidity, hyperthermia, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) when taken in combination with an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Such reactions may occur when these drugs are given concurrently or in close proximity.

Effect of CYP2D6 Inhibitors on Strattera (Atomoxetine Hydrochloride)

In extensive metabolizers (EMs), inhibitors of CYP2D6 (e.g., fluoxetine, paroxetine, and quinidine) increase atomoxetine steady-state plasma concentrations to exposures similar to those observed in poor metabolizers (PMs). In EM individuals treated with paroxetine or fluoxetine, the AUC of atomoxetine is approximately 6- to 8-fold and Css,max is about 3- to 4-fold greater than atomoxetine alone.

In vitro studies suggest that coadministration of cytochrome P450 inhibitors to PMs will not increase the plasma concentrations of atomoxetine.

Pressor Agents

Because of possible effects on blood pressure, Strattera (Atomoxetine Hydrochloride) capsules should be used cautiously with pressor agents (e.g., dopamine, dobutamine).


Atomoxetine (Strattera) should be administered with caution to patients being treated with systemically-administered (oral or intravenous) albuterol (or other beta2 agonists) because the action of albuterol on the cardiovascular system can be potentiated resulting in increases in heart rate and blood pressure. Albuterol (600 mcg IV over 2 hours) induced increases in heart rate and blood pressure. These effects were potentiated by atomoxetine (60 mg BID for 5 days) and were most marked after the initial coadministration of albuterol and atomoxetine. However, these effects on heart rate and blood pressure were not seen in another study after the coadministration with inhaled dose of albuterol (200-800 mcg) and atomoxetine (80 mg QD for 5 days) in 21 healthy Asian subjects who were excluded for poor metabolizer status.

Effect of Atomoxetine on P450 Enzymes

Atomoxetine (Strattera) capsules did not cause clinically important inhibition or induction of cytochrome P450 enzymes, including CYP1A2, CYP3A, CYP2D6, and CYP2C9. CYP3A Substrate (e.g., Midazolam)

Coadministration of Strattera (60 mg BID for 12 days) with midazolam, a model compound for CYP3A4 metabolized drugs (single dose of 5 mg), resulted in 15% increase in AUC of midazolam. No dose adjustment is recommended for drugs metabolized by CYP3A.

CYP2D6 Substrate (e.g., Desipramine)

Coadministration of Strattera (40 or 60 mg BID for 13 days) with desipramine, a model compound for CYP2D6 metabolized drugs (single dose of 50 mg), did not alter the pharmacokinetics of desipramine. No dose adjustment is recommended for drugs metabolized by CYP2D6.


Consumption of ethanol with Atomoxetine HCl (Strattera) did not change the intoxicating effects of ethanol.


Coadministration of methylphenidate with Atomoxetine HCl (Strattera) capsules did not increase cardiovascular effects beyond those seen with methylphenidate alone.

Drugs Highly Bound to Plasma Protein

In vitro drug-displacement studies were conducted with atomoxetine and other highly-bound drugs at therapeutic concentrations. Atomoxetine did not affect the binding of acetylsalicylic acid, warfarin, phenytoin, or diazepam to human albumin. Similarly, these compounds did not affect the binding of atomoxetine to human albumin.

Drugs that Affect Gastric pH

Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) had no effect on Atomoxetine Hydrochloride (Strattera) bioavailability.

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