Paroxetine Atomoxetine

D6 Desipramine, dextromethorphan, atomoxetine Paroxetine, quinidine, fluoxetine (use of PM vs. EM subjects) None identified... 

Monoamine oxidase inhibitors Paroxetine Protriptyline Sertraline Venlafaxine Stimulants Atomoxetine Dextroamphetamine Methylphenidate Modaflnil Pemoline... 

Medications that enhance norepinephrine activity can do so in one of several ways. First, they can block the reuptake of norepinephrine back into the nerve cell once it has been released. This keeps the norepinephrine in the synapse longer and therefore makes it more active. The tricyclic antidepressants (TCAs), duloxetine (Cymbalta), and venlafaxine (Effexor) act in this manner, as does paroxetine (Paxil) at higher doses. Atomoxetine (Strattera), a treatment for ADHD, also works in this way. 

Atomoxetine has not been shown to exert clinically significant inhibition of CYP 1A2, CYP 2C9, CYP 2D6, and CYP 3A isoenzymes (Sauer et al. 2004). However, paroxetine, a potent CYP 2D6 inhibitor, has been shown to increase plasma concentrations of atomoxetine and significantly increase the half-life of atomoxetine approximately 2.5-fold in extensive 2D6 metabolizers (Belle et al. 2002). Caution should be used when administering atomoxetine to patients taking albuterol or pressor agents because atomoxetine may potentiate the cardiovascular effects of albuterol or pressor agents. 

Adderall XR (package insert). Wayne, PA, Shire US Inc, 2004 Angrist B, d Hollosy M, Sanfilipo M, et al Central nervous system stimulants as symptomatic treatments for AIDS-related neuropsychiatric impairment. J Clin Psychophamiacol 12 268—272, 1992 Arnold LE, Lindsay RL, Connors CK, et al A douhle-hlind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention-deficit hyperactivity disorder. I Am Acad Child Adolesc Psychiatry 14 542—554, 2004 Belle DJ, Ernest CS, Sauer JM, et al Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. I Clin Pharmacol 42 1219-1227, 2002... 

Belle DJ, Ernest CS, Sauer JM, et al. Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. J Clin Pharmacol 2002 42 1219-27. 

SSRIs ATOMOXETINE t plasma concentrations and risk of adverse effects (abdominal pain, vomiting, nausea, fatigue, irritability) Atomoxetine is a selective norepinephrine reuptake inhibitor, t plasma concentrations due to inhibition of CYP2D6 by fluoxetine and paroxetine (potent), fluvoxamine and sertraline (less potent) and escitalopram and citalopram (weak) Avoid concurrent use. The interaction is usually severe with fluoxetine and paroxetine... 

Initiate therapy of these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. hydrocodone, oxycodone, desipramine, paroxetine, chlorpheniramine, mesoridazine, alprenolol, amphetamines, atomoxetine)... 

Plasma concentrations of atomoxetine may be increased by drugs that inhibit CYP450 2D6 (e.g., paroxetine, fluoxetine), so atomoxetine dose may need to be reduced if co-administered... 

SSRIs fluoxetine, paroxetine, sertraline Others bupropion, mirtazapine, nefazodone, trazodone, atomoxetine... 

Atomoxetine (CYP2D6) Fluoxetine Paroxetine AUC increase 6- to 8-fold in EM no change PM expected 21... 

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

Paroxetine markedly increases atomoxetine levels in extensive metabolisers of CYP2D6. Fluoxetine also raises atomoxetine levels. There is a possibility that this may increase adverse effects, and a slower titration of atomoxetine dose is su ested for patients taking paroxetine and other CYP2D6 inhibitors. 

Paroxetine 20 mg daily for 17 days, with atomoxetine 20 mg twice daily on days 12 to 17, was given to 22 healthy subjects who were extensive metabolisers of the cytochrome P450 isoenzyme CYP2D6 (most common phenotype). Paroxetine increased the AUC of atomoxetine 6.5-fold, increas l the maximum plasma level by 3.5-fold, and increased the elimination half-life by 2.5-fold, when compared with atomoxetine alone. No changes in paroxetine pharmacokinetics were seen. The pharmacokinetics of atomoxetine with paroxetine in these subjects was similar to that previously seen with atomoxetine alone in poor metaboliser subjects. 

Atomoxetine is extensively metabolised by CYP2D6, an isoenzyme that shows polymorphism, with up to 10% of the population lacking an active form (poor metabolisers). Paroxetine inhibits CYP2D6, and thereby increases atomoxetine levels in those with an extensive metaboliser phenotype. It would not be expected to have any effect in poor metabolisers. Fluoxetine can similarly inhibit CYP2D6. 

---