Version May 2024
Atomoxetine increased the risk of suicidal ideation in short-term studies in children or adolescents with attention deficit hyperactivity disorder (ADHD). Anyone considering the use of atomoxetine in a child or adolescent must balance this risk with the clinical need. Comorbidities occurring with ADHD may be associated with an increase in the risk of suicidal ideation and/or behavior. Closely monitor patients who are started on therapy for suicidality (suicidal thinking and behavior), clinical worsening, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the prescribing health care provider. Atomoxetine is approved for ADHD in pediatric and adult patients. Atomoxetine is not approved for major depressive disorder (MDD).
Pooled analyses of short-term (6- to 18-week), placebo-controlled trials of atomoxetine in children and adolescents (12 trials involving more than 2,200 patients, including 11 trials in ADHD and 1 trial in enuresis) have revealed a greater risk of suicidal ideation early during treatment in those receiving atomoxetine compared with placebo. The average risk of suicidal ideation in patients receiving atomoxetine was 0.4% compared with none in placebo-treated patients. No suicides occurred in these trials.
Attention-deficit/hyperactivity disorder (ADHD):
Note: Generally reserved for patients with a history of substance use disorder or those who cannot tolerate or do not have a sufficient response to preferred agents (Ref).
Oral: Initial: 40 mg once daily. Increase after ≥3 days to 80 mg/day; may administer as a single daily dose in the morning or as 2 evenly divided doses in the morning and late afternoon/early evening. After an additional 2 to 4 weeks, may increase based on response and tolerability to 100 mg/day in 1 or 2 divided doses. Maximum: 100 mg/day.
Dosage adjustment based on CYP2D6 metabolizer status: Patients known to be CYP2D6 poor metabolizers: Initial: 40 mg/day; if tolerating therapy but inadequate response, may increase after ≥4 weeks to 80 mg/day.
Orthostatic hypotension, neurogenic (off-label use):
Note: May be useful for management of symptoms unresponsive to volume repletion in patients with normal or elevated serum norepinephrine levels (Ref).
Oral: Initial: 10 mg twice daily; may increase to 18 mg twice daily, if needed, based on response and tolerability (Ref). Note: Although short-term trials demonstrated efficacy of a fixed dose of 18 mg once daily, an initial dose of 10 mg twice daily, adjusted if needed, may be preferred for individualizing therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Mild impairment (Child-Pugh class A): No dosage adjustment provided in manufacturer's labeling.
Moderate impairment (Child-Pugh class B): Reduce dose to 50% of normal dose.
Severe impairment (Child-Pugh class C): Reduce dose to 25% of normal dose.
Use has not been evaluated in older adults.
(For additional information see "Atomoxetine: Pediatric drug information")
Attention-deficit/hyperactivity disorder: Note: Use is suggested in patients who are intolerant of or lack a response to stimulants; an adequate stimulant trial of at least 6 weeks is suggested prior to initiating atomoxetine; not typically used first-line (Ref). Atomoxetine may be an optimal selection for patients with tics or Tourette syndrome comorbidity, or if stimulant diversion or misuse is a concern (Ref). As a nonstimulant drug, atomoxetine may take longer to provide therapeutic effect than stimulant therapy (Ref).
Children ≥6 years and Adolescents:
Patient weight ≤70 kg: Oral: Initial: ~0.5 mg/kg/day; increase after a minimum of 3 days to ~1.2 mg/kg/day; may administer either once daily in the morning or in 2 evenly divided doses in the morning and late afternoon/early evening; maximum daily dose: 1.4 mg/kg/day or 100 mg/day, whichever is less. Note: Doses >1.2 mg/kg/day have not been shown to provide additional benefit.
Dosage adjustment in patients known to be CYP2D6 poor metabolizers: Oral: Initial: 0.5 mg/kg/day; if tolerating therapy but inadequate response, may increase after a minimum of 4 weeks to 1.2 mg/kg/day.
Patient weight >70 kg: Oral: Initial: 40 mg once daily; increase after a minimum of 3 days to ~80 mg daily; may administer either once daily in the morning or in 2 evenly divided doses in morning and late afternoon/early evening. If optimal response has not been achieved after an additional 2 to 4 weeks of therapy, may increase dose up to a maximum daily dose: 100 mg/day.
Dosage adjustment in patients known to be CYP2D6 poor metabolizers: Oral: Initial: 40 mg once daily; if tolerating therapy but inadequate response, may increase after a minimum of 4 weeks to 80 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents: No dosage adjustments are recommended.
Children ≥6 years and Adolescents:
Moderate hepatic impairment: Administer 50% of normal dose.
Severe hepatic impairment: Administer 25% of normal dose.
Atomoxetine has been associated with aggressive behavior and hostility in pediatric patients, particularly with initiation. Overall, these events have occurred infrequently in trials with atomoxetine-treated children and adolescents, making it difficult to assess causality. Of note, some studies have not observed an increased risk. Irritability, which may be a precursor to hostility and aggression, has been observed more frequently with use. In addition, a case report of activation syndrome, described as an aggravation of preexisting attention-deficit/hyperactivity disorder (ADHD) symptoms in addition to new-onset aggression, irritability, disinhibition, and insomnia, has been reported in a child treated with a relatively high dose of atomoxetine (Ref).
Mechanism: Unknown; aggressive behavior, by itself, is affected by many factors, such as genetics, environmental and psychosocial factors, cognition, hormones, and neurotransmitters. Atomoxetine, a potent inhibitor of presynaptic norepinephrine transporter may play a role in impulsive aggression through its actions on norepinephrine. It has also been suggested that increased irritability and aggression is due to incompletely treated ADHD and/or related to the condition of ADHD or other comorbidities and not related to pharmacologic therapy (Ref).
Onset: Intermediate; in one long-term safety and tolerability trial in children and adolescents with ADHD treated for ≥3 years, irritability and aggression occurred more frequently within the first month of treatment and then tended to subside over time; reports of hostility were observed sporadically over time (Ref). One meta-analysis also observed a mean onset of 4 weeks following therapy initiation (Ref).
Risk factors:
• ADHD, regardless of medication use, has been associated with aggressive behavior (Ref).
Atomoxetine, similar to the CNS stimulants used for attention-deficit/hyperactivity disorder (ADHD), has been associated with rare, but serious cardiovascular events, including sudden cardiac death (SCD), acute myocardial infarction (MI), or cerebrovascular accident (Ref). However, a large retrospective cohort study in children and young adults (2 to 24 years) showed no evidence that current use of an ADHD medication (including atomoxetine) was associated with an increased risk of serious cardiovascular events compared to non-use (Ref). Other cohort studies in children and adolescents with ADHD have also failed to demonstrate an increased risk for SCD, MI, or stroke (Ref). Consistent with these results, retrospective cohort studies in adults also found no evidence of an increased risk of MI, SCD, or stroke associated with current users of ADHD medication compared to non-users (Ref). Atomoxetine use has been shown to cause statistically significant increases in blood pressure and increased heart rate (HR) (Ref). Most pediatric patients experience a moderate increase in BP and/or HR, although in 8% to 12% of patients, a more significant increase occurred (ie, BP (≥15 to 20 mm Hg) and HR (≥20 bpm) (Ref). In adult and pediatric patients, average increases in HR, systolic BP, and diastolic BP range from 3 to 10 bpm, 3 to 8 mm Hg and 2 to 14 mm Hg respectively (Ref). The manufacturer generally recommends against atomoxetine use in children and adolescents with serious cardiac conditions (eg, structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities) and to consider avoiding use in adults with serious cardiac conditions. The American Academy of Pediatrics/American Heart Association (AAP/AHA) recommends that children undergo a cardiovascular evaluation prior to therapy initiation (Ref).
Mechanism: Has not been fully elucidated, but it has been suggested that atomoxetine, due to its selective inhibition of the presynaptic norepinephrine transporter, may increase blood pressure by way of increased norepinephrine in peripheral sympathetic neurons in select individuals (Ref).
Onset: Varied; in studies, observed increases in HR and BP have occurred early in treatment (initial 12 to 24 weeks of treatment) but tend to stabilize over time (Ref).
Risk factors:
Serious cardiovascular events:
• Patients with serious structural heart disease, including cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems (manufacturer’s labeling) Note: ADHD is common in children with congenital structural cardiac disease (Ref)
Increases in BP and/or HR:
• Patients with central autonomic failure (may increase the risk of hypertension) (Ref)
• CYP2D6 poor metabolizers (potential risk factor; conflicting evidence exists) (Ref)
• Preexisting hypertension
• Preexisting tachycardia
• Known cardiovascular disease
• Known cerebrovascular disease
Growth retardation (weight and height) have been observed in atomoxetine-treated pediatric patients during the early phase of treatment, but effects tend to be reversible or recover over the long term. Specifically, data suggests that decreases in body weight and/or height may occur in the first 2 years of atomoxetine treatment in pediatric patients; however, weight and growth recovers or starts to recover over 2 to 5 years of atomoxetine (Ref).
Mechanism: Unknown since growth is affected by many factors; however, it has been suggested that reductions in weight due to atomoxetine may be secondary to decreased appetite, resulting from the GI side effects associated with atomoxetine (eg, nausea, vomiting, upper abdominal pain); these GI side effects are typically highest in the first 1 to 3 months of treatment (Ref).
Onset: In one long-term, open-label study, atomoxetine-treated patients weighed less than expected compared to the population norm as early as 1 month following treatment initiation, with a maximum effect on weight observed at 15 months. This same trial observed an effect on height at 12 months with a maximum effect at 18 months (Ref).
Risk factors:
• Pediatric patients who are above average in height and weight before treatment have shown a more persistent decrease in growth in open-label studies (potential risk factor) (Ref)
Hepatobiliary events, typically described as mild increased serum alanine aminotransferase and increased serum aspartate aminotransferase (without jaundice or other signs of liver failure) have been observed with atomoxetine use (Ref). There are also case reports of severe hepatic injury, including acute hepatitis and acute hepatic failure with one case of acute liver failure requiring emergency liver transplantation with atomoxetine (Ref). Therapy discontinuation is warranted in any patient with signs of jaundice and/or laboratory evidence of liver injury.
Mechanism: Unknown, but atomoxetine is metabolized primarily by CYP2D6 in the liver, therefore, metabolic idiosyncrasy due to a toxic intermediate or byproduct has been suggested as a potential mechanism. In some cases, drug-induced autoimmune hepatitis has also been suggested as a potential mechanism (Ref).
Onset: Varied; most reports of severe liver injury describe an onset of within 3 to 12 weeks following initiation, although it has been observed as early as 2 days after therapy or as late as 23 months following initiation (Ref).
Rare cases of priapism have been reported in pediatric patients treated with atomoxetine alone, and in pediatric patients taking atomoxetine and risperidone concomitantly (Ref).
Mechanism: Has not been elucidated; atomoxetine may cause priapism through central dopaminergic and peripheral noradrenergic actions (Ref).
Onset: Varied; in one case report, onset occurred 2 weeks following atomoxetine initiation and the morning after a dose increase (Ref) and in another case report, onset occurred several years after being maintained on a stable dose of atomoxetine (Ref).
Risk factors:
• Hematological dyscrasias (eg, sickle cell disease) (Ref)
• Malignancies (Ref)
• Perineal trauma (Ref)
• Illicit substance use or alcohol (Ref)
• Concomitant medications associated with priapism (psychotropic drugs such as trazodone, antihypertensive such as prazosin) (Ref)
Treatment-emergent psychosis (predominately manifested as auditory hallucination), mania, or hypomania have been reported in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) receiving therapeutic doses of atomoxetine. In the vast majority of cases, these events have occurred in patients with no identifiable risk factor (Ref). Of note, bipolar disorder is highly comorbid with ADHD and there may be a potential risk for induction of manic symptoms with atomoxetine use (Ref).
Mechanism: Norepinephrine hyperactivity has been suggested as a potential mechanism for inducing mania; atomoxetine increases norepinephrine concentration in the brain by its inhibition of the presynaptic norepinephrine transporter. Psychosis has been attributed to dopaminergic mechanisms; it has been suggested that atomoxetine may affect dopamine levels indirectly by its inhibition of the presynaptic norepinephrine transporter and it has also been suggested that due to structural similarities between norepinephrine and dopamine, the norepinephrine transporter may also reuptake dopamine (Ref).
Onset: Varied; data from an analysis of events in patients with ADHD treated with either atomoxetine or a stimulant, onset of psychiatric symptoms occurred within days or weeks of therapy initiation in ~2/3 of the postmarketing reports to Medwatch. In the remainder 1/3 of patients, onset began after months, except for a few cases where symptom onset occurred after years of treatment (Ref).
Prolonged QT interval on ECG has been reported postmarketing according to the manufacturer’s labeling and in a single published case report (Ref). However, in clinical trials, there is no consistent evidence that atomoxetine results in clinically significant QTc prolongation at therapeutic doses in children and adolescents (Ref). However, some literature has shown clinically significant QTc prolongation in certain populations. One placebo-controlled study in healthy CYP2D6 poor metabolizer adult males (atomoxetine is metabolized primarily by CYP2D6) did not observe a clinically significant change in QTc on day 7 compared with baseline, but did observe statistically significant increase in QTc observed with increasing atomoxetine concentrations (Ref). In the setting of overdose, case reports suggest that atomoxetine may increase the QT interval at supratherapeutic doses; however, atomoxetine was combined with other agents known to have QT prolongation potential or inhibit CYP2D6 (Ref).
Mechanism: In overdose settings, atomoxetine has been shown to inhibit human ether-à-go-go-related gene (hERG) potassium channels, leading to prolongation of the QT interval (Ref).
Risk factors:
Atomoxetine specifically:
• CYP2D6 poor metabolizers (potential risk factor) (Ref)
• Females (potential risk factor) (Ref)
• Higher/supratherapeutic doses (potential risk factor) (Ref)
Drug-induced QTc prolongation/torsades de pointes (TdP) (in general):
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with a reduced ejection fraction) (Ref)
• History of drug-induced TdP (Ref)
• Genetic defects of cardiac ion channels (Ref)
• Congenital long QT syndrome (Ref)
• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Electrolyte disturbances (eg, hypokalemia, hypocalcemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Coadministration of multiple medications (≥2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QTc prolonging medications (Ref)
• Substance use (Ref)
A meta-analysis observed a statically significant higher incidence of suicidal ideation with atomoxetine use in children and adolescent patients with attention-deficit/hyperactivity disorder (ADHD) compared to placebo. No deaths by suicide were reported in the clinical trials used in this meta-analysis although 1 patient attempted suicide (Ref). Other data or retrospective analysis have also observed an association with atomoxetine and suicidal ideation in pediatric patients with ADHD (Ref). However, one observational study failed to find a statistically significant increased risk of suicidal ideation in atomoxetine-treated children and adolescents (Ref) and one cohort study did not find an increased risk of suicidal events in pediatric patients treated with atomoxetine (to determine if increased risk of suicidal ideation observed in trials translated into an increased risk of suicide and suicide attempts). To date, there is no evidence for an increased risk of suicidal behavior or ideation in adults treated with atomoxetine (Ref).
Mechanism: Unknown; although it has been suggested that the relationship between ADHD and suicidal ideation (if one exists) may be related to underlying impulsivity and aggression and/or indirectly mediated by comorbidities such as depression rather than related to medication use (Ref).
Onset: In one meta-analysis, time to onset of the suicide-related events ranged from 9 to 32 days (Ref).
Risk factors:
• Patients with ADHD, regardless of medication use, are often considered to be at a higher risk for suicide compared to the general population and typically have an increased prevalence of many psychiatric comorbidities, such as depression, conduct disorder, and substance abuse, which are associated with an increased risk of suicide, regardless of medication use (Ref)
• Children and adolescents with a history of serious suicidal attempt or depression (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages as reported in children, adolescents, and adults; some adverse reactions are increased in CYP2D6 poor or extensive metabolizers.
>10%:
Cardiovascular: Increased diastolic blood pressure (≥15 mm Hg: 5% to 22%), increased heart rate (≥20 bpm: 10% to 23%) (Fay 2019) (table 1), increased systolic blood pressure (≥15 mm Hg: 4% to 13%)
|
Drug (Atomoxetine) |
Placebo |
Population |
Comments |
|---|---|---|---|
|
23% |
12% |
Children and adolescents |
Heart rate ≥20 bpm; proportion of patients meeting threshold at any one time during clinical trial |
|
12% |
4% |
Children and adolescents |
Heart rate ≥20 bpm; endpoint of trial |
|
22% |
8% |
Adults |
Heart rate ≥20 bpm; proportion of patients meeting threshold at any one time during clinical trial |
|
10% |
2% |
Adults |
Heart rate ≥20 bpm; endpoint of trial |
Dermatologic: Hyperhidrosis (4% to 15%)
Gastrointestinal: Abdominal pain (7% to 18%), constipation (1% to 11%), decreased appetite (15% to 23%), nausea (7% to 26%), vomiting (4% to 11%), xerostomia (17% to 35%)
Genitourinary: Erectile dysfunction (8% to 21%)
Nervous system: Drowsiness (8% to 11%), headache (19%), insomnia (1% to 19%) (table 2)
|
Drug (Atomoxetine) |
Placebo |
Population |
Number of Patients (Atomoxetine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
11% |
N/A |
Children and adolescents |
N/A |
N/A |
CYP2D6 poor metabolizers |
|
6% |
N/A |
Children and adolescents |
N/A |
N/A |
CYP2D6 extensive metabolizers |
|
3% |
N/A |
Children and adolescents |
N/A |
N/A |
Middle insomnia; CYP2D6 poor metabolizers |
|
1% |
N/A |
Children and adolescents |
N/A |
N/A |
Middle insomnia; CYP2D6 extensive metabolizers |
|
19% |
N/A |
Adults |
N/A |
N/A |
CYP2D6 poor metabolizers |
|
15% |
8% |
Adults |
1,697 |
1,560 |
N/A |
|
11% |
N/A |
Adults |
N/A |
N/A |
CYP2D6 extensive metabolizers |
|
5% |
N/A |
Adults |
N/A |
N/A |
Middle insomnia; CYP2D6 poor metabolizers |
|
3% |
N/A |
Adults |
N/A |
N/A |
Middle insomnia; CYP2D6 extensive metabolizers |
|
3% |
N/A |
Adults |
N/A |
N/A |
Terminal insomnia; CYP2D6 poor metabolizers |
|
1% |
N/A |
Adults |
N/A |
N/A |
Terminal insomnia; CYP2D6 extensive metabolizers |
1% to 10%:
Cardiovascular: Cold extremity (1% to 3%), orthostatic hypotension (≤2%), palpitations (3%), syncope (≤3%), tachycardia (≤2%) (table 3)
|
Drug (Atomoxetine) |
Placebo |
Population |
Number of Patients (Atomoxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
0.3% |
0% |
Children and adolescents |
1,597 |
934 |
|
2% |
0.5% |
Adults |
540 |
402 |
Dermatologic: Excoriation of skin (2% to 4%), skin rash (2%)
Endocrine & metabolic: Decreased libido (3%), hot flash (3%), increased thirst (2%), weight loss (2% to 7%)
Gastrointestinal: Anorexia (3%), dyspepsia (4%)
Genitourinary: Dysmenorrhea (3%), dysuria (2%), ejaculatory disorder (2% to 6%), urinary hesitancy (6%), urinary retention (1% to 6%)
Nervous system: Abnormal dreams (4%), chills (3%), depression (4% to 7%), dizziness (5% to 8%), emotional lability (1% to 2%), fatigue (6% to 10%), hostility (≤2%) (table 4), irritability (5% to 6%) (table 5), jitteriness (2% to 5%), paresthesia (3%), sedated state (2% to 4%), sleep disturbance (3% to 7%)
|
Drug (Atomoxetine) |
Placebo |
Population |
Number of Patients (Atomoxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
2% |
1% |
Children and adolescents |
1,308 |
806 |
|
0.4% |
0.3% |
Adults |
1,697 |
1,560 |
|
Drug (Atomoxetine) |
Placebo |
Population |
Number of Patients (Atomoxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
6% |
3% |
Children and adolescents |
1,597 |
934 |
|
5% |
3% |
Adults |
1,697 |
1,560 |
Neuromuscular & skeletal: Tremor (1% to 5%)
Ophthalmic: Blurred vision (1% to 4%), conjunctivitis (1% to 3%), mydriasis (1% to 2%)
Miscellaneous: Therapeutic response unexpected (2%)
<1%: Nervous system: Delusion, hallucination, mania (Henderson 2004), psychotic symptoms (including psychosis and auditory hallucinations) (Mosholder 2009), seizure (Finsterer 2020), suicidal ideation (Bangs 2008)
Frequency not defined:
Cardiovascular: Flushing, sinus tachycardia
Dermatologic: Pruritus, urticaria
Endocrine & metabolic: Menstrual disease, orgasm abnormal
Gastrointestinal: Dysgeusia, flatulence
Genitourinary: Pollakiuria, prostatitis, testicular pain, urinary urgency
Nervous system: Agitation, anxiety, restlessness, sensation of cold
Neuromuscular & skeletal: Asthenia, muscle spasm
Postmarketing:
Cardiovascular: Acute myocardial infarction (Seifi 2011), cardiomyopathy (takotsubo) (Yamaguchi 2014), cerebrovascular accident, prolonged QT interval on ECG (Yamaguchi 2014), Raynaud's disease (Gökçen 2013)
Dermatologic: Alopecia
Endocrine & metabolic: Change in libido, growth retardation
Genitourinary: Pelvic pain (male), priapism (Armstrong 2015, Goetz 2014)
Hepatic: Hepatic failure (can be acute hepatic failure) (Erdogan 2011), hepatic injury (severe) (Erdogan 2011, Lim 2006), hepatitis (Lim 2006), hepatotoxicity (Lim 2006), increased serum alanine aminotransferase (Abrams 2021, Bangs 2008), increased serum aspartate aminotransferase (Abrams 2021, Bangs 2008), jaundice (Lim 2006)
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction
Nervous system: Abnormal sensory symptoms, aggressive behavior (Donnelly 2009, Polzer 2007), akathisia (Yazici 2014), depressed mood, hypoesthesia, hypomania (Henderson 2004), impulsivity, lethargy, overstimulation (activation syndrome; Karakaya 2021), panic attack, tic disorder (Ledbetter 2005)
Neuromuscular & skeletal: Rhabdomyolysis
Hypersensitivity to atomoxetine or any component of the formulation; use with or within 14 days of MAO inhibitors; narrow-angle glaucoma; current or history of pheochromocytoma; severe cardiac or vascular disorders in which the condition would be expected to deteriorate with clinically important increases in blood pressure (eg, 15 to 20 mm Hg) or heart rate (eg, 20 beats/minute).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Symptomatic cardiovascular diseases, moderate to severe hypertension; advanced arteriosclerosis; uncontrolled hyperthyroidism
Disease-related concerns:
• Attention-deficit/hyperactivity disorder and comorbidities: Randomized, controlled trials have demonstrated that atomoxetine does not worsen anxiety in patients with existing anxiety disorders or tics related to Tourette disorder.
• Bipolar disorder: Patients with bipolar disorder or risk factors for bipolar disorder (eg, family history of mania and depression) may be at increased risk for mania or mixed episodes during therapy.
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustments necessary in moderate and severe hepatic insufficiency.
• Urinary retention: Use with caution in patients with a history of urinary retention or bladder outlet obstruction; may cause urinary retention/hesitancy.
Special populations:
• CYP2D6 poor metabolizers: When atomoxetine is being used to treat attention-deficit/hyperactivity disorder, dosage adjustments are recommended in CYP2D6 poor metabolizers; these patients have increased exposure to atomoxetine.
Other warnings/precautions:
• Attention-deficit/hyperactivity disorder treatment: Appropriate use: Recommended to be used as part of a comprehensive treatment program for attention deficit disorders.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Strattera: 10 mg, 18 mg
Strattera: 25 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Strattera: 40 mg, 60 mg, 80 mg [contains corn starch, fd&c blue #2 (indigotine,indigo carmine)]
Strattera: 100 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg, 100 mg
Yes
Capsules (Atomoxetine HCl Oral)
10 mg (per each): $14.22 - $14.23
18 mg (per each): $14.22 - $14.23
25 mg (per each): $14.22 - $14.23
40 mg (per each): $7.60 - $15.47
60 mg (per each): $15.45 - $15.47
80 mg (per each): $16.67 - $16.69
100 mg (per each): $16.67 - $16.69
Capsules (Strattera Oral)
10 mg (per each): $15.82
18 mg (per each): $15.82
25 mg (per each): $15.82
40 mg (per each): $17.18
60 mg (per each): $17.18
80 mg (per each): $18.54
100 mg (per each): $18.54
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Strattera: 10 mg [DSC], 18 mg
Strattera: 25 mg [DSC], 40 mg [DSC], 60 mg, 80 mg, 100 mg [DSC] [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg, 100 mg
Oral: Administer without regard to food. Do not crush, chew, or open capsule; swallow whole. Note: Atomoxetine is an ocular irritant; if capsule is opened inadvertently and contents come into contact with eye, flush eye immediately with water and obtain medical advice; wash hands and any potentially contaminated surface as soon as possible.
Oral: May be administered without regard to food. Do not crush, chew, or open capsule; swallow whole with water or other liquids. Note: Atomoxetine is an ocular irritant; if capsule is opened inadvertently and contents come into contact with eye, flush eye immediately with water and obtain medical advice; wash hands and any potentially contaminated surface as soon as possible.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021411s048lbl.pdf#page=19, must be dispensed with this medication.
Attention-deficit/hyperactivity disorder: Treatment of attention-deficit/hyperactivity disorder (ADHD).
Orthostatic hypotension, neurogenic
Atomoxetine may be confused with atorvastatin.
Substrate of CYP2C19 (minor), CYP2D6 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Beta2-Agonists: Atomoxetine may enhance the tachycardic effect of Beta2-Agonists. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Atomoxetine. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Iobenguane Radiopharmaceutical Products: Selective Norepinephrine Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination
Monoamine Oxidase Inhibitors: May enhance the neurotoxic (central) effect of Atomoxetine. Risk X: Avoid combination
Ozanimod: May enhance the hypertensive effect of Selective Norepinephrine Reuptake Inhibitors. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Sympathomimetics: Atomoxetine may enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Appropriate contraception is recommended for sexually active women of childbearing potential (Heiligenstein 2003). An agent other than atomoxetine is preferred for the treatment of attention-deficit/hyperactivity disorder (ADHD) in women planning a pregnancy (Larsen 2015).
In comparison to other agents used for the treatment of attention-deficit/hyperactivity disorder (ADHD), information related to atomoxetine use in pregnancy is limited (Bro 2015; Haervig 2014; Heiligenstein 2003; Ornoy 2018).
If medication is needed for the treatment of ADHD during pregnancy, an agent other than atomoxetine is preferred. Consider discontinuing or changing treatment in patients who become pregnant during atomoxetine therapy (Larsen 2015).
Data collection to monitor pregnancy and infant outcomes following exposure to atomoxetine is ongoing. Health care providers are encouraged to enroll patients exposed to atomoxetine during pregnancy in the National Pregnancy Registry for ADHD medications at 1-866-961-2388.
It is not known if atomoxetine is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. An agent other than atomoxetine is preferred for the treatment of attention-deficit/hyperactivity disorder (ADHD) in women who are breastfeeding (Larsen 2015).
Liver enzymes (upon signs/symptoms of liver dysfunction and for several weeks after discontinuation for liver dysfunction). Cardiac evaluation should be completed at baseline (medical history and family history of sudden death or ventricular arrhythmia, physical exam to assess for cardiac disease; further evaluation such as ECG if findings suggest cardiac disease) and on any patient who develops exertional chest pain, unexplained syncope, and any symptom of cardiac disease during treatment. Monitor BP and heart rate (baseline, following dose increases and periodically during treatment); growth (weight and height) and appetite in children; weight in adults; sleep and behavioral changes. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial few months of therapy or during periods of dosage adjustments (increases or decreases). Screen for risk factors for bipolar disorder (eg, personal or family history of bipolar disorder, mania, hypomania and depression) prior to therapy initiation; monitor for signs/symptoms of mania/hypomania during therapy.
Timing of serum samples: In normal, intermediate, and ultrarapid CYP26 metabolizers or in patients with unknown CYP2D6 metabolizer status, draw peak plasma concentrations 1 to 2 hours after dose. In intermediate CYP2D6 metabolizers, consider drawing peak plasma concentrations 2 to 4 hours after dose in patients with lower enzyme activity or if the *10 allele is present. For poor CYP2D6 metabolizers, draw peak plasma concentrations 4 hours after dose (Brown 2019; Hiemke 2018).
Therapeutic reference range: 200 to 1,000 ng/mL (782 to 3,910 nmol/L) (Hiemke 2018). Note: There is no clear correlation with therapeutic levels and efficacy or tolerability; base dosing on therapeutic response as opposed to serum concentrations (Hazell 2009; Michelson 2007). However, therapeutic drug levels may be useful in patients with CYP2D6 polymorphisms that have a poor treatment response (Brown 2019).
Laboratory alert level: 2,000 ng/mL (7,820 nmol/L) (Hiemke 2018).
Selectively inhibits the reuptake of norepinephrine (Ki 4.5 nM) with little to no activity at the other neuronal reuptake pumps or receptor sites.
Note: The pharmacokinetics in pediatric patients ≥6 years of age have been shown to be similar to those of adult patients.
Duration of action: Up to 24 hours (Jain 2017)
Absorption: Rapid
Distribution: Vd: IV: 0.85 L/kg
Protein binding: 98%, primarily albumin
Metabolism: Hepatic, via CYP2D6 and CYP2C19; forms metabolites (4-hydroxyatomoxetine, active, equipotent to atomoxetine; N-desmethylatomoxetine, limited activity); Note: CYP2D6 poor metabolizers have atomoxetine AUCs that are ~10-fold higher and peak concentrations that are ~fivefold greater than extensive metabolizers; 4-hyroxyatomoxetine plasma concentrations are very low (extensive metabolizers: 1% of atomoxetine concentrations; poor metabolizers: 0.1% of atomoxetine concentrations
Bioavailability: 63% in extensive metabolizers; 94% in poor metabolizers
Half-life elimination: Atomoxetine: 5 hours (up to 24 hours in poor metabolizers); Active metabolites: 4-hydroxyatomoxetine: 6-8 hours; N-desmethylatomoxetine: 6-8 hours (34-40 hours in poor metabolizers)
Time to peak, plasma: 1-2 hours; delayed 3 hours by high-fat meal
Excretion: Urine (80%, as conjugated 4-hydroxy metabolite; <3% is excreted unchanged); feces (17%)
Altered kidney function: Extensive metabolizers with ESRD had higher systemic exposure (approximately a 65% increase), but there was no difference when exposure was corrected for mg/kg dose.
Hepatic function impairment: AUC is increased in extensive metabolizers with moderate or severe hepatic impairment.
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