Strattera - Clinical Pharmacology

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Ethnic origin —Ethnic origin did not influence atomoxetine disposition (except that PMs are more common in Caucasians).

Drug-Drug Interactions

CYP2D6 activity and atomoxetine plasma concentration —

Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine. In EMs, inhibitors of CYP2D6 increase atomoxetine steady-state plasma concentrations to exposures similar to those observed in PMs. Dosage adjustment of STRATTERA in EMs may be necessary when coadministered with CYP2D6 inhibitors, e. g., paroxetine, fluoxetine, and quinidine (see Drug-Drug Interactions under PRECAUTIONS). In vitro studies suggest that coadministration of cytochrome P450 inhibitors to PMs will not increase the plasma concentrations of atomoxetine.

Effect of atomoxetine on P450 enzymes —

Atomoxetine did not cause clinically important inhibition or induction of cytochrome P450 enzymes, including CYP1A2, CYP3A, CYP2D6, and CYP2C9. Albuterol — 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 (see Drug-Drug Interactions under PRECAUTIONS).

Alcohol —

Consumption of ethanol with STRATTERA did not change the intoxicating effects of ethanol.

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.

Methylphenidate —

Coadministration of methylphenidate with STRATTERA did not increase cardiovascular effects beyond those seen with methylphenidate alone.

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.