Dosing and uses of Strattera (atomoxetine)
Adult dosage forms and strengths
capsule
- 10mg
- 18mg
- 25mg
- 40mg
- 60mg
- 80mg
- 100mg
Attention-Deficit/Hyperactivity Disorder
40 mg PO once daily initially; increased after ≥3 days to 80 mg PO once daily or divided q12hr; may be increased to ≤100 mg if optimal response is not achieved
Dosing considerations
- When drug is coadministered with strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or used in patients known to be poor CYP2D6 metabolizers, decrease dosage; initiate with 40 mg/day, but do not exceed 80 mg/day
Dosing Modifications
Renal impairment: Dosage adjustment not necessary
Mild hepatic impairment (Child-Pugh class A): Dosage adjustment not necessary
Moderate hepatic impairment (Child-Pugh class B): Decrease initial and target dosage by 50%
Severe hepatic impairment (Child-Pugh class C): Decrease initial and target dosage by 75%
Pediatric dosage forms and strengths
capsule
- 10mg
- 18mg
- 25mg
- 40mg
- 60mg
- 80mg
- 100mg
Attention-Deficit/Hyperactivity Disorder
>6 years and ≤70 kg: 0.5 mg/kg PO once daily; increased after ≥3 days to target dosage of ~1.2 mg/kg PO once daily or divided q12hr; total daily dose not to exceed 1.4 mg/kg or 100 mg, whichever is less; no benefit observed with higher doses
>70 kg: 40 mg PO once daily initially; increased after ≥3 days to 80 mg PO once daily or divided q12hr; if necessary, may be increased after 2-4 additional weeks to 100 mg PO once daily
Dosing considerations
- When drug is coadministered with strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or used in patients known to be poor CYP2D6 metabolizers, decrease dosage
- ≤70 kg: 0.5 mg/kg/day initially; increased to usual target dosage of 1.2 mg/kg/day only if symptoms fail to improve after 4 weeks and initial dosage is well tolerated
- >70 kg: 40 mg/day initially; not to exceed 80 mg/day
Administration
Must be swallowed whole with aid of liquids; must not be chewed, divided, or crushed
Administer once daily in morning, with or without food
Strattera (atomoxetine) adverse (side) effects
>10%
Xerostomia (dry mouth) (21%)
Headache (2-19%)
Abdominal pain (7-18%)
Decreased appetite (11-16%)
Insomnia (2-15%)
Cough (11%)
Somnolence (11%)
Vomiting (3-11%)
1-10%
Nausea (10%)
Increases in blood pressure (BP; ≥15-20 mm Hg) and heart rate (HR; ≥20 beats/min) (5-10%)
Erectile dysfunction (9%)
Hot flashes (8%)
Dizziness (5-8%)
Urinary hesitation or retention (7%)
Decreased weight (4-7%)
Depression (4-7%)
Irritability (<6%)
Dyspepsia (4%)
Ejaculation disorder (3%)
Sinus headache (3%)
Constipation (2%)
Dermatitis (2%)
Menstrual disorder (2%)
Mood swings (1-2%)
Postmarketing Reports
Paresthesia
Cardiovascular: QT prolongation, syncope
Peripheral vascular: Raynaud phenomenon
General: Lethargy
Neurologic: Hypesthesia, paresthesia in children and adolescents, sensory disturbances, tics
Psychiatric: Depression and depressed mood, anxiety
Seizures: Cases include patients with preexisting seizure disorders and those with identified risk factors for seizures, as well as patients with neither history of nor identified risk factors for seizures; exact relation between atomoxetine and seizures is difficult to evaluate because of uncertainty about background risk of seizures in patients with attention-deficit/hyperactivity disorder (ADHD)
Skin: Hyperhidrosis
Urogenital: Male pelvic pain, urinary hesitation or retention in children and adolescents
Musculoskeletal: Rhabdomyolysis
Warnings
Black box warnings
Atomoxetine use has been associated with increased risk of suicidal ideation in short-term studies in children or adolescents with ADHD; this risk must be balanced against clinical need in patients with ADHd
Monitor patients closely for suicidal thinking and behavior, clinical worsening, or unusual behavioral changes; families and caregivers should be advised of need for close observation and communication with prescribing healthcare provider
Average risk of suicidal ideation in patients receiving atomoxetine has been shown to be ~0.4% (5/1357 patients)
Contraindications
Hypersensitivity
Narrow-angle glaucoma
Administration concomitantly with or within 14 days of monoamine oxidase inhibitor (MAOI) therapy; risk of potentially fatal reaction, including hyperthermia, myoclonus, altered mental status, and neuroleptic malignant syndrome (NMS)-like symptoms
Pheochromocytoma: Serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with current or previous pheochromocytoma
Severe cardiovascular disorders where condition would deteriorate because BP increases by 15-20 mm Hg or HR increases by 20 beats/min; risk is greater in poor CYP2D6 metabolizers
Cautions
If drug is given concomitantly with CYP2D6 inhibitor, wait 4 weeks after initiation before adjusting dosage
Liver injury reported within 120 days of initiation of atomoxetine; patients may present with elevated liver enzymes (>20 × ULN) and jaundice with significantly elevated bilirubin levels (>2 × ULN), followed by recovery upon discontinuance of atomoxetine
Orthostatic hypotension and syncope reported
Risk of suicidal thoughts in children and adolescents
Small risk of allergic reaction
Use caution in hypertension, tachycardia (see Contraindications)
Sudden deaths, stroke, and myocardial infarction reported in patients with structural cardiac abnormalities or other serious heart problems taking stimulants at usual doses; patients should have a careful history and physical exam to assess for presence of cardiovascular disease; consider not using atomoxetine in adults with clinically significant cardiac abnormalities
Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation
Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder because of concern for possible induction of mixed/manic episode in such patients
Aggressive behavior or hostility is often observed in children and adolescents with ADHD; monitor for the appearance of or worsening of aggressive behavior or hostility
Monitor growth of children ages 7 to 10 years during treatment with stimulants; may need to interrupt therapy in patients not growing or gaining weight as expected
Urinary hesitancy or sexual dysfunction may occur
Rare instances of priapism reported, sometimes necessitating surgical intervention; typically not reported during initiation but often occurring subsequent to dosage increase; immediate medical attention should be sought for abnormally sustained or frequent and painful erections
Drug can be discontinued without being tapered
Hypesthesia, paresthesia in children and adolescents, sensory disturbances
Rare reports of allergic reactions, including anaphylactic reactions, angioneurotic edema, urticaria, and rash
Use with caution in patietns with bipolar disorder, history of hypertension, hepatic impairment, existing anxiety disorder, history of urinary retention, or tics related to Tourette disorder
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown whether drug is excreted in milk; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Strattera (atomoxetine)
Mechanism of action
Selective inhibition of presynaptic norepinephrine reuptake
Absorption
Bioavailability: 63-94%
Onset: 2-4 wk
Peak plasma time: 1-2 hr
Distribution
Vd: 0.85 L/kg (IV)
Protein bound: 98%
Vd: 0.85 L/kg
Metabolism
Metabolized in liver by CYP2D6
Metabolites: 4-Hydroxyatomoxetine (equipotent), N-desmethylatomoxetine (less potent)
Elimination
Half-life: 5.2 hr
Total body clearance: 0.35 L/hr/kg
Excretion: Urine (80%), feces (17%)
