STRATTERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STRATTERA (STRATTERA).
Selective norepinephrine reuptake inhibitor (NRI). Increases norepinephrine and dopamine in the prefrontal cortex by blocking the norepinephrine transporter.
| Metabolism | Primarily via CYP2D6 to 4-hydroxyatomoxetine; active metabolite with similar activity. Also undergoes glucuronidation. |
| Excretion | Renal excretion of metabolites (80-97% as conjugated metabolites in urine, <1% unchanged atomoxetine; fecal excretion <3%). |
| Half-life | Terminal half-life 5.2 hours (extensive metabolizers, CYP2D6 normal) and 21.6 hours (poor metabolizers); clinical context: requires twice-daily dosing in extensive metabolizers, poor metabolizers may need lower doses. |
| Protein binding | 98% bound to albumin; 1% bound to alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd 0.85 L/kg; indicates distribution throughout total body water with some tissue binding. |
| Bioavailability | Oral bioavailability 63% for atomoxetine; decreased to 40-50% in poor metabolizers due to reduced CYP2D6 activity. |
| Onset of Action | Oral: 1-2 hours after single dose for initial effect; full therapeutic response may take 1-4 weeks. |
| Duration of Action | Duration ~12 hours after twice-daily dosing; immediate-release formulation requires twice-daily dosing for continuous coverage. |
Initial 40 mg orally once daily, increase after minimum 3 days to 80 mg once daily, then after additional 2-4 weeks to 100 mg once daily if needed. Maximum 100 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; use with caution in GFR <30 mL/min or ESRD, consider reducing dose. |
| Liver impairment | Child-Pugh Class A: reduce dose to 50% of normal; Class B: reduce to 25% of normal; Class C: contraindicated. |
| Pediatric use | Weight ≤70 kg: initial 0.5 mg/kg/day orally for 3 days, then increase to 1.2 mg/kg/day. Maximum 1.4 mg/kg/day or 100 mg, whichever less. Weight >70 kg: same as adult dosing. |
| Geriatric use | No specific dose adjustment; start at lowest adult dose and titrate slowly due to possible increased sensitivity or comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STRATTERA (STRATTERA).
| Breastfeeding | Atomoxetine is excreted in human milk. In a study of 8 nursing women, the milk-to-plasma ratio (M/P) was approximately 0.4. The estimated infant dose is about 0.4% of the maternal weight-adjusted dose. Caution should be exercised when administered to a nursing woman; consider developmental and health benefits of breastfeeding along with mother's clinical need and potential adverse effects on the breastfed child. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. Atomoxetine and its metabolites cross the placenta in rats. In animal studies, there was evidence of decreased fetal weight and increased incidence of skeletal abnormalities at doses less than the maximum human dose. Pregnancy Category C. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
Increased risk of suicidal ideation in children and adolescents with ADHD; monitor for clinical worsening, suicidality, or unusual behavioral changes.
| Serious Effects |
["Hypersensitivity to atomoxetine or any components","Use with or within 14 days of MAOIs (risk of hypertensive crisis)","Narrow-angle glaucoma","Pheochromocytoma (risk of hypertensive crisis)","Severe untreated cardiovascular disease (e.g., prolonged QT interval, severe hypertension)"]
| Precautions | ["Suicidal thoughts/behaviors in children and adolescents","Severe liver injury (elevated transaminases, jaundice)","Cardiovascular effects (increased heart rate, blood pressure; caution in hypertension, tachycardia, or cardiovascular disease)","Emergence of new psychotic or manic symptoms","Potential for urinary retention (especially in males with prostatic hypertrophy)","Use caution in patients with bipolar disorder (may induce mixed/manic episodes)","Aggressive behavior or hostility","Allergic reactions including angioedema","Effects on growth (weight loss, height delay in children)"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly. Assess for signs of hepatotoxicity including elevated liver enzymes, jaundice, dark urine, or unexplained flu-like symptoms. In pregnancy, monitor fetal growth and well-being with ultrasound if clinically indicated. Consider monitoring for maternal weight gain and signs of preeclampsia. |
| Fertility Effects | In animal studies, no adverse effects on fertility were observed in rats at doses up to 100 mg/kg/day (8 times the maximum human dose on mg/m² basis). Human data on fertility effects are lacking. Atomoxetine may cause sexual dysfunction in males (ejaculatory dysfunction, erectile dysfunction) which could impair fertility; however, no direct effect on fertility has been established. |