BLACK BOX WARNING
- suicidal ideation in children and adolescents during initial treatment
atomoxetine
Brand: Strattera
⚠ BBW Prototype Drug
Drug Class: selective norepinephrine reuptake inhibitor (NRI)
Drug Family: CNS stimulant
Subclass: non-stimulant ADHD medication
Organ Systems: cns
Mechanism of Action
Selectively inhibits the norepinephrine transporter (NET) in the prefrontal cortex, increasing norepinephrine availability in circuits involved in attention and impulse control. Unlike stimulants, it also modestly increases dopamine in the prefrontal cortex through indirect NET-mediated mechanisms, without directly increasing striatal dopamine (therefore no significant abuse potential).
NET (norepinephrine transporter)
Indications
- ADHD (children ≥6 years, adolescents, and adults)
Contraindications
- concurrent MAOI use
- narrow-angle glaucoma
- pheochromocytoma
Adverse Effects
Common
- decreased appetite
- nausea
- somnolence (especially at initiation)
- headache
- dry mouth
- dizziness
- urinary retention (adults)
Serious
- suicidal ideation (pediatric)
- hepatotoxicity (rare)
- serious cardiovascular effects (elevated HR and BP)
- priapism (rare)
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~63-94% depending on CYP2D6 metabolizer status |
| Distribution | protein binding ~98%; primarily albumin |
| Metabolism | primarily CYP2D6; 4-hydroxyatomoxetine (equipotent active metabolite in extensive metabolizers); poor metabolizers have 10-fold higher AUC |
| Excretion | primarily renal |
| Half-life | 5.2 hours (extensive metabolizers); 21.6 hours (poor metabolizers) |
| Onset | therapeutic effect may require 2-6 weeks (not immediate like stimulants) |
| Peak | 1-2 hours |
| Duration | 24 hours (once-daily dosing may work due to long half-life in PMs) |
| Protein Binding | 98% |
| Vd | 0.85 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAOIs | hypertensive crisis | contraindicated |
| CYP2D6 inhibitors (fluoxetine, paroxetine) | poor-metabolizer-like pharmacokinetics; dose reduction needed | major |
| albuterol | potential additive cardiovascular effects | moderate |
Nursing Considerations
- Onset of therapeutic effect takes 2-6 weeks — patients and families must be counseled that atomoxetine is not immediately effective like stimulants; premature discontinuation based on lack of immediate response is common.
- Monitor liver function tests if patient develops jaundice, dark urine, or abdominal pain; rare hepatotoxicity has been reported.
- Assess for suicidal ideation at every visit during the first weeks of therapy per the pediatric BBW; document assessment.
- A key clinical advantage over stimulants is the lack of abuse potential (not a controlled substance); this makes it preferred in patients with substance use disorder or in situations where controlled substance access is difficult.
Clinical Pearls
- Atomoxetine is the only non-stimulant ADHD medication approved for adults as well as children; its non-controlled status and once-daily dosing make it an important option in settings where stimulant diversion is a concern.
- CYP2D6 poor metabolizers (7-10% of Caucasians) have 10-fold higher atomoxetine exposure than extensive metabolizers; starting at lower doses and monitoring for adverse effects is warranted when CYP2D6 metabolizer status is unknown or when CYP2D6 inhibitors are co-administered.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.