ATOMOXETINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATOMOXETINE HYDROCHLORIDE (ATOMOXETINE HYDROCHLORIDE).
Selective norepinephrine reuptake inhibitor (NRI) that increases noradrenergic neurotransmission in the prefrontal cortex.
| Metabolism | Primarily metabolized by CYP2D6; forms 4-hydroxyatomoxetine (active) via oxidative metabolism. |
| Excretion | Primarily renal: approximately 80% of a dose is excreted in urine, with 2-3% as unchanged drug; 17% fecal. |
| Half-life | Terminal elimination half-life is approximately 5 hours in CYP2D6 extensive metabolizers; in poor metabolizers, half-life is prolonged to about 21-24 hours. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.85 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is approximately 63% in extensive metabolizers; may be higher in poor metabolizers due to reduced first-pass metabolism. |
| Onset of Action | Oral: clinical effects on ADHD symptoms may be observed within 1-2 weeks of starting therapy, but full therapeutic response may take 4-8 weeks. |
| Duration of Action | Sustained throughout the day with once-daily dosing; clinical effects last approximately 24 hours, allowing for once-daily administration. |
Initial 40 mg orally once daily; increase after minimum 3 days to 80 mg/day; maximum 100 mg/day if inadequate response after 2-4 weeks.
| Dosage form | CAPSULE |
| Renal impairment | No adjustment for mild to moderate impairment; severe (eGFR <30 mL/min/1.73 m²) or ESRD: use 40 mg/day initial, titrate cautiously; not studied in dialysis. |
| Liver impairment | Child-Pugh Class A: reduce dose by 50%; Class B: 75% reduction; Class C: contraindicated. |
| Pediatric use | Weight ≤70 kg: start 0.5 mg/kg/day, increase after 3 days to 1.2 mg/kg/day; maximum 1.4 mg/kg/day or 100 mg/day. Weight >70 kg: same as adult dosing. |
| Geriatric use | Insufficient data; use cautious low initial doses (40 mg/day) with gradual titration; monitor for cardiovascular effects and tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ATOMOXETINE HYDROCHLORIDE (ATOMOXETINE HYDROCHLORIDE).
| Breastfeeding | Excreted in human milk; M/P ratio unknown. Relative infant dose estimated <0.2% of maternal weight-adjusted dose. Monitor infant for agitation, poor feeding, decreased weight gain. Consider risks of untreated maternal condition. |
| Teratogenic Risk | Pregnancy Category C. Animal studies show fetal harm (e.g., reduced viability, low birth weight) at doses 7-23x human exposure. No adequate human studies. First trimester: increased risk of congenital anomalies not confirmed. Second/third trimester: risk of preterm delivery, low birth weight, neonatal adaptation syndrome (respiratory distress, feeding difficulty, irritability). Consider risk-benefit. |
■ FDA Black Box Warning
Increased risk of suicidal ideation in children and adolescents with ADHD; monitor for clinical worsening, suicidality, or unusual changes in behavior.
| Serious Effects |
Hypersensitivity to atomoxetine, concurrent use or within 14 days of MAOIs, narrow-angle glaucoma, and phaeochromocytoma.
| Precautions | Suicidal thoughts and behaviors, severe liver injury, cardiovascular effects (increased blood pressure and heart rate), allergic reactions, and urinary retention. |
| Food/Dietary | No significant food interactions. Grapefruit juice does not affect atomoxetine. Can be taken with or without food. |
| Clinical Pearls |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate throughout pregnancy. Assess fetal growth via ultrasound, monitor for preterm labor. Neonatal monitoring for withdrawal symptoms (irritability, tachypnea, feeding intolerance) for 48 hours after delivery. |
| Fertility Effects | Animal studies: no impairment of fertility in male or female rats at clinically relevant doses. Human data: limited; no evidence of significant impairment. Consider effects on libido or erectile function in males. |
| Atomoxetine is a selective norepinephrine reuptake inhibitor (NRI) used for ADHD. It has no abuse potential and is not a controlled substance. Onset of therapeutic effect may take 2-4 weeks. Monitor for suicidal ideation, especially in children and adolescents. CYP2D6 poor metabolizers have higher exposure; consider lower starting dose. Avoid use in narrow-angle glaucoma. May cause orthostatic hypotension; advise patients to rise slowly. Can increase heart rate and blood pressure; monitor baseline and periodically. Contraindicated with MAOIs within 14 days. Use caution with hepatic impairment; reduce dose in moderate impairment, not recommended in severe. |
| Patient Advice | Take atomoxetine exactly as prescribed, usually once or twice daily. · May be taken with or without food. · Do not crush or chew capsules; swallow whole. · Effect may take several weeks to be fully noticeable. · Avoid alcohol as it may worsen side effects. · Report any suicidal thoughts or unusual changes in mood immediately. · Stand up slowly from sitting or lying down to prevent dizziness. · Notify doctor if you experience fast or irregular heartbeat, difficulty urinating, or yellowing of skin/eyes. · Do not stop abruptly; discuss with doctor before discontinuing. · Keep out of reach of children. |