Atomoxetine Hydrochloride

Approved Indications:

• Attention-Deficit/Hyperactivity Disorder (ADHD):
• Adults and Pediatric Patients (≥6 years): For the treatment of ADHD, including inattentive, hyperactive-impulsive, or combined presentation.
• Adolescents and Adults: Can also improve executive function and reduce emotional dysregulation associated with ADHD.

Clinically Accepted Off-label Uses:

• Treatment-Resistant Depression (Adjunctive)
• Binge Eating Disorder (BED)
• Cognitive Dysfunction in Traumatic Brain Injury
• Narcolepsy (adjunct or alternative therapy)

Route of Administration: Oral
Frequency: Once or twice daily with or without food

Adults (≥18 years):

• Initial: 40 mg/day
• Maintenance: 80 mg/day (after ≥3 days); max 100 mg/day

Children and Adolescents (6 to <70 kg):

• Initial: 0.5 mg/kg/day
• Titrate to 1.2 mg/kg/day (target dose)
• Max: 1.4 mg/kg/day or 100 mg/day, whichever is less

Children and Adolescents (≥70 kg):

• Initial: 40 mg/day
• Increase after ≥3 days to 80 mg/day
• Max: 100 mg/day

Hepatic Impairment:

• Moderate (Child-Pugh B): Reduce dose to 50%
• Severe (Child-Pugh C): Reduce dose to 25%

Renal Impairment:

• No dosage adjustment generally required, but monitor closely in severe renal dysfunction

Elderly:

• Use with caution; not widely studied in patients >65 years

Duration: Long-term use may be continued if therapeutic benefits persist

Atomoxetine is a selective norepinephrine reuptake inhibitor (NRI). It blocks the presynaptic norepinephrine transporter (NET), thereby increasing extracellular concentrations of norepinephrine in the prefrontal cortex. This action enhances attention, reduces hyperactivity, and improves impulse control. Unlike stimulants, it has minimal dopaminergic activity in the striatal regions, reducing abuse potential.

• Absorption: Rapid; peak plasma concentration (Tmax) within 1–2 hours
• Bioavailability: ~63% due to significant first-pass hepatic metabolism
• Distribution: Widely distributed; protein binding ~98%
• Metabolism: Primarily via hepatic CYP2D6 enzyme
• Active Metabolite: 4-hydroxyatomoxetine (equally potent)
• Half-life:
• Extensive metabolizers: ~5.2 hours
• Poor metabolizers (CYP2D6 deficient): ~21.6 hours
• Elimination: Primarily urine (>80%) as metabolites

• Pregnancy: Not assigned a specific FDA pregnancy category under new labeling rules; animal studies show adverse fetal effects at high doses. Use only if potential benefit justifies risk.
• Lactation: Excreted in human milk. Potential for serious adverse reactions in nursing infants. Avoid use or discontinue breastfeeding if treatment is necessary.
• Caution: Use only if clearly needed; consult a specialist for pregnant or lactating patients.

• Primary: Non-stimulant ADHD Medication
• Subclass: Selective Norepinephrine Reuptake Inhibitor (NRI)
• Drug Schedule: Not a controlled substance

• Known hypersensitivity to Atomoxetine or its components
• Narrow-angle glaucoma
• Current use of or use within 14 days of monoamine oxidase inhibitors (MAOIs)
• Pheochromocytoma or history of pheochromocytoma
• Severe cardiovascular disorders (e.g., symptomatic heart disease)

• Suicidal Ideation: Risk especially in children and adolescents; monitor closely during initiation and dose changes
• Cardiovascular Effects: Increased heart rate and blood pressure; screen for underlying heart disease
• Liver Injury: Rare but potentially serious hepatotoxicity; discontinue if signs occur
• Growth Suppression: Monitor height and weight in pediatric patients
• Psychiatric Events: Can worsen anxiety, aggression, mania, or psychosis
• Urinary Retention: May occur, especially in males or those with BPH

Common (≥10%):

• CNS: Insomnia, headache, dizziness, fatigue
• GI: Dry mouth, decreased appetite, nausea, vomiting, abdominal pain
• CV: Increased heart rate and blood pressure

Less Common (<10%):

• Sexual dysfunction (e.g., erectile dysfunction, decreased libido)
• Menstrual irregularities
• Urinary retention
• Weight loss

Serious/Rare:

• Hepatotoxicity
• Suicidal ideation
• Syncope
• Severe allergic reactions (angioedema, urticaria)

• CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine): May increase Atomoxetine levels; dose adjustment may be required
• MAO Inhibitors: Contraindicated due to hypertensive crisis risk
• Albuterol (systemic): May potentiate CV effects (e.g., tachycardia)
• Antihypertensives: May reduce their efficacy
• Alcohol: CNS depressant effects may be additive

• Recent Labeling: FDA advises heightened monitoring for suicidal ideation in pediatric and adolescent patients.
• Guidelines (APA, NICE, AACAP): Atomoxetine is a recommended first-line treatment for ADHD in patients where stimulant use is contraindicated or not preferred.
• New Safety Note: EMA recommends monitoring liver function periodically in long-term users due to rare hepatotoxicity.

• Store at 20°C to 25°C (68°F to 77°F)
• Excursions permitted between 15°C to 30°C
• Protect from excessive heat and humidity
• Keep in original packaging until use
• No refrigeration or reconstitution required