indication

For the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) alone or in combination with behavioral treatment, as an adjunct to psychological, educational, social, and other remedial measures.

pharmacology

Atomoxetine is the first non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). Atomoxetine is classified as a norepinephrine reuptake inhibitor, and is approved for use in children, adolescents, and adults. However, its efficacy has not been studied in children under six years old. Its advantage over stimulants for the treatment of ADHD is that it has less abuse potential than stimulants, is not scheduled as a controlled substance and has proven in clinical trials to offer 24 hour coverage of symptoms associated with ADHD in adults and children.

mechanism of action

The precise mechanism by which atomoxetine produces its therapeutic effects in Attention-Deficit/Hyperactivity Disorder (ADHD) is unknown, but is thought to be related to selective inhibition of the pre-synaptic norepinephrine transporter, as determined through in-vitro studies. Atomoxetine appears to have minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors.

toxicity

The most commonly reported symptoms accompanying acute and chronic overdoses are somnolence, agitation, hyperactivity, abnormal behavior, and gastrointestinal symptoms.

biotransformation

Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine. 4-Hydroxyatomoxetine is equipotent to atomoxetine as an inhibitor of the norepinephrine transporter but circulates in plasma at much lower concentrations (1% of atomoxetine concentration in EMs and 0.1% of atomoxetine concentration in PMs).

absorption

Atomoxetine is rapidly absorbed after oral administration, with absolute bioavailability of about 63% in EMs and 94% in PMs. Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) have no effect on atomoxetine bioavailability. Absorption is minimally affected by food.

half life

5 hours

drug interactions

Amiodarone: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Chloroquine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Cocaine: CYP2D6 Inhibitors (Strong) such as cocaine may increase the serum concentration of atomoxetine. Initiate atomoxetine at a reduced dose (patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. The dose should only be increased to usual doses if symptoms fail to improve after 4 weeks. Patients established on atomoxetine therapy may require dosage reductions and should be monitored for increased levels/adverse effects with initiation/dose increase of a strong CYP2D6 inhibitor.

Diphenhydramine: Diphenhydramine, a moderate CYP2D6 inhibitor, may increase the therapeutic and adverse effects of atomoxetine by decreasing its metabolism.

Fluoxetine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Fluphenazine: Risk of additive CNS depressant effects. Monitor for increased CNS depression during concomitant therapy.

Haloperidol: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Isocarboxazid: Possible severe adverse reaction with this combination

Lomustine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Mibefradil: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Paroxetine: The CYP2D6 inhibitor, paroxetine, may increase the effect and toxicity of atomoxetine.

Perphenazine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Phenelzine: Possible severe adverse reaction with this combination

Propoxyphene: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Quinacrine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Quinidine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Quinidine barbiturate: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Quinine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Rasagiline: Possible severe adverse reaction with this combination

Ritonavir: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Terbinafine: Terbinafine, a CYP2D6 inhibitor, may reduce the metabolism and clearance of Atomoxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Atomoxetine if Terbinafine is initiated, discontinued or dose changed.

Thioridazine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Tranylcypromine: The MAO inhibitor, Tranylcypromine, may increase the central neurotoxic effects of the Atomoxetine. These agents should not be administered within 14 days of each other.

Triprolidine: The CNS depressants, Triprolidine and Atomoxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Vinorelbine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine

Yohimbine: The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine