Brand name: Strattera
Drug class: Respiratory and CNS Stimulants

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Selective norepinephrine reuptake inhibitor.

Uses for Atomoxetine

Attention Deficit Hyperactivity Disorder

Treatment of ADHD, alone or combined with behavioral treatment, as an adjunct to psychological, educational, social, and other remedial measures in carefully selected adults and children ≥6 years of age.

Atomoxetine Dosage and Administration

General

• Can discontinue atomoxetine without tapering dosage.

Administration

Oral Administration

Administer orally once daily in the morning or in 2 equally divided doses in the morning and late afternoon/early evening.

Administer without regard to meals.

Ocular irritant; swallow capsules whole, do not open capsules or sprinkle contents on food.

If a dose is missed, take the missed dose as soon as it is remembered, but the amount taken within a 24-hour period should not exceed the prescribed total daily dosage.

Dosage

Available as atomoxetine hydrochloride; dosage expressed in terms of atomoxetine.

Pediatric Patients

ADHD

Oral

Children and adolescents weighing ≤70 kg: Initially, approximately 0.5 mg/kg daily. Increase dosage after ≥3 days to target dosage of approximately 1.2 mg/kg daily (do not exceed 100 mg daily).

Children and adolescents weighing >70 kg: Initially, 40 mg daily. Increase dosage after ≥3 days to target dosage of approximately 80 mg daily. If optimum response has not been achieved after 2–4 additional weeks of therapy, may increase dosage to maximum of 100 mg daily.

Adults

ADHD

Oral

Initially, 40 mg daily. Increase dosage after ≥3 days to target dosage of approximately 80 mg daily. If optimum response has not been achieved after 2–4 additional weeks of therapy, may increase dosage to maximum of 100 mg daily.

Prescribing Limits

Pediatric Patients

ADHD

Oral

Children and adolescents weighing ≤70 kg: Maximum 100 mg or 1.4 mg/kg daily (whichever is less); dosages >1.2 mg/kg daily have not been shown in clinical trials to result in additional therapeutic benefit.

Children and adolescents weighing >70 kg: Maximum 100 mg daily; dosages >100 mg daily have not been shown in clinical trials to result in additional therapeutic benefit. Safety of single doses >120 mg and total daily dosages >150 mg has not been established.

Long-term efficacy (i.e., >12 months in pediatric patients 6–15 years of age or >9 weeks in pediatric patients 16–18 years of age) not established. If used for extended periods, periodically reevaluate the usefulness of long-term therapy.

Adults

ADHD

Oral

Maximum 100 mg daily; dosages >100 mg daily have not been shown in clinical trials to result in additional therapeutic benefit. Safety of single doses >120 mg and total daily dosages >150 mg has not been established.

Long-term efficacy (i.e., >10 weeks) not established. If used for extended periods, periodically reevaluate the usefulness of long-term therapy.

Special Populations

Hepatic Impairment

Reduce initial and target dosages by 50% in patients with moderate hepatic impairment (Child-Pugh class B) and by 75% in those with severe hepatic impairment (Child-Pugh class C).

Cautions for Atomoxetine

Contraindications

• Known hypersensitivity to atomoxetine or any ingredient in the formulation.

• Current or recent (within 2 weeks) therapy with MAO inhibitor. Allow ≥2 weeks to elapse after discontinuing atomoxetine before initiating MAO inhibitor therapy. (See Specific Drugs under Interactions.)

• Angle-closure glaucoma.

Warnings/Precautions

Warnings

Suicidality Risk

Increased risk of suicidal thinking observed in a pooled analysis of short-term clinical trials in children and adolescents with ADHD. (See Pediatric Use under Cautions.) Not known whether risk extends to long-term use of the drug.

Similar analysis of data from adults with ADHD or major depressive disorder found no increased risk of suicidal ideation or behavior in those receiving atomoxetine.

Balance risk of suicidality against the clinical need for the drug.

Monitor pediatric patients closely for clinical worsening, suicidal ideation or behaviors, or unusual changes in behavior, particularly during the first few months of therapy and following dosage adjustment. Monitoring should include daily observation by family members and caregivers and frequent contact with the prescribing clinician, particularly if the patient’s behavior changes or is a concern.

Manufacturer recommends face-to-face contact between clinicians and patients or their family members or caregivers at least weekly during the first 4 weeks of therapy and then every other week for the next 4 weeks, with subsequent face-to-face contact at 12 weeks and as clinically indicated thereafter; additional contact via telephone may be appropriate between visits.

Consider discontinuance of therapy in patients with emergent suicidality or manifestations that may be precursors to emerging suicidality (e.g., anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania), particularly if such manifestations are severe or abrupt in onset or were not part of the patient’s presenting symptoms.

Sensitivity Reactions

Hypersensitivity Reactions

Angioedema, urticaria, and rash reported rarely.

Other Warnings and Precautions

Severe Hepatic Injury

Severe hepatic injury rarely reported; manifested by increased hepatic enzymes (up to 40 times ULN) and jaundice (bilirubin up to 12 times ULN). Risk of progression to acute hepatic failure resulting in death or requiring liver transplantation in a small percentage of patients. Adverse hepatic effects may occur several months after atomoxetine initiation; laboratory abnormalities may continue to worsen for several weeks after discontinuance.

Determine hepatic enzyme concentrations after first manifestation of hepatic dysfunction (e.g., pruritus, dark urine, jaundice, right upper quadrant tenderness, unexplained flu-like symptoms). Discontinue atomoxetine in patients with jaundice or laboratory evidence of hepatic injury and do not reinitiate.

Sudden Death and Serious Cardiovascular Events

Sudden unexplained death, stroke, and MI reported in adults with ADHD receiving usual dosages of atomoxetine; sudden death also reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of the drug.

Thoroughly review medical history (including evaluation for family history of sudden death or ventricular arrhythmia) and perform physical examination in all children, adolescents, and adults being considered for atomoxetine therapy; if initial findings suggest presence of cardiac disease, perform further cardiac evaluation (e.g., ECG, echocardiogram).

In general, avoid use in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, CAD, or other serious cardiac conditions.

Patients who develop exertional chest pain, unexplained syncope, or other manifestations suggestive of cardiac disease during atomoxetine therapy should undergo prompt cardiac evaluation.

Precipitation of Psychotic Symptoms

Psychotic symptoms (e.g., hallucinations, delusional thinking) may occur with usual dosages in children and adolescents without prior history of psychotic illness. If psychotic symptoms occur, consider causal relationship to atomoxetine, and discontinue therapy as appropriate.

Precipitation of Manic Symptoms

May precipitate mixed or manic episodes in ADHD patients with comorbid bipolar disorder; use with caution in these patients. Prior to initiating therapy, carefully screen patients with ADHD and comorbid depressive symptoms to identify risk for bipolar disorder; screening should include a detailed psychiatric history (e.g., family history of suicide, bipolar disorder, or depression).

Manic symptoms may occur with usual dosages in children and adolescents without prior history of mania. If manic symptoms occur, consider causal relationship to atomoxetine, and discontinue therapy as appropriate.

Cardiovascular Effects

Increased BP and heart rate reported in children, adolescents, and adults. Use with caution in patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. Measure BP and pulse rate before initiation of atomoxetine, following any increase in dosage, and periodically during therapy.

Orthostatic hypotension and syncope reported; use with caution in patients with conditions that would predispose them to hypotension.

Peripheral Vascular Effects

Exacerbation or precipitation of Raynaud’s phenomenon reported.

GU Effects

Possible urinary retention and urinary hesitation.

Growth Effects

Monitor growth of pediatric patients receiving atomoxetine. Potential for temporary suppression of normal height and/or weight patterns following initiation of therapy. (See Pediatric Use under Cautions.)

Behavioral Effects

Aggressive behavior and hostility frequently are observed in pediatric patients with ADHD and have been reported in patients receiving drug therapy (including atomoxetine) for the disorder.

Monitor patients beginning treatment for ADHD for the appearance or worsening of aggressive behavior or hostility.

Priapism

Priapism reported rarely in pediatric and adult patients; requires prompt medical attention. (See Advice to Patients.)

Tics

In a controlled study, atomoxetine did not worsen tics in patients with ADHD and comorbid Tourette’s disorder.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats; not known whether atomoxetine is distributed into human milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established in children <6 years of age.

Increased risk of suicidal ideation observed in a pooled analysis of 12 short-term controlled clinical trials in pediatric patients with ADHD (11 studies) or enuresis (1 study); risk of suicidal ideation was about 0.4% in those receiving atomoxetine versus 0% in those receiving placebo. One child receiving the drug attempted suicide; no completed suicides were reported. All events representing suicidal behavior or thinking occurred in children ≤12 years of age and occurred during the first month of therapy. Not known whether the risk extends to long-term use of the drug. Balance risk of suicidality against the clinical need for the drug. (See Suicidality Risk under Cautions.)

Sudden death reported in children and adolescents with structural cardiac abnormalities or other serious cardiac conditions receiving usual dosages of stimulants. (See Sudden Death and Serious Cardiovascular Events under Cautions.)

Potential for temporary (e.g., 9–12 months) suppression of normal height and/or weight patterns following initiation of atomoxetine therapy in pediatric patients; rebound in height and weight gains reported with continued therapy. Pattern observed regardless of metabolizer phenotype (poor or extensive metabolizer of the drug) or pubertal status upon initiation of therapy. Monitor growth of patients receiving atomoxetine therapy.

Geriatric Use

Safety and efficacy not established.

Hepatic Impairment

Increased systemic exposure to atomoxetine in patients with moderate or severe hepatic impairment. (See Hepatic Impairment under Dosage and Administration and Special Populations under Pharmacokinetics.)

Common Adverse Effects

In children and adolescents, abdominal pain, decreased appetite, vomiting, somnolence, nausea, fatigue, irritability, dizziness.

In adults, dry mouth, nausea, insomnia, decreased appetite, constipation, fatigue, erectile dysfunction, hot flush, urinary hesitation and/or retention, dysmenorrhea.

Drug Interactions

Metabolized principally by CYP2D6. Does not cause clinically important inhibition or induction of CYP enzymes, including 1A2, 3A, 2D6, and 2C9.

Drugs Affecting Hepatic Microsomal Enzymes

Potential for increased plasma atomoxetine concentrations during concomitant therapy with CYP2D6 inhibitors in individuals with extensive metabolizer CYP2D6 phenotype (concentrations may be similar to those achieved in poor metabolizers).

If used concomitantly with a potent CYP2D6 inhibitor or in patients with poor metabolizer CYP2D6 phenotype, initiate atomoxetine therapy at usual initial daily dosage (approximately 0.5 mg/kg daily in children and adolescents weighing ≤70 kg; 40 mg daily in adults and children and adolescents weighing >70 kg); increase dosage to usual target dosage (approximately 1.2 mg/kg daily [maximum 100 mg daily] in children and adolescents weighing ≤70 kg; 80 mg daily in adults and children and adolescents weighing >70 kg) only if ADHD symptoms fail to improve after 4 weeks of therapy and initial dosage is well tolerated.

Specific Drugs

Atomoxetine Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration, with peak plasma concentration attained in approximately 1–2 hours.

Absolute bioavailability is 63% in extensive metabolizers of CYP2D6 substrates and 94% in poor metabolizers.

In patients with the poor metabolizer CYP2D6 phenotype, AUC and peak plasma concentrations of atomoxetine are 10- and 5-fold greater, respectively, than in extensive metabolizers.

Food

Standard high-fat meal decreases rate but not extent of absorption in adults. In children and adolescents, food reduces peak plasma concentration by 9%.

Special Populations

In patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment, systemic exposure is increased twofold or fourfold, respectively.

Distribution

Extent

Distributed into milk in animals; not known whether atomoxetine distributes into human milk or crosses the placenta.

Plasma Protein Binding

98% (principally albumin).

Elimination

Metabolism

Principally metabolized by CYP2D6 to an equipotent metabolite (4-hydroxyatomoxetine) that circulates in plasma at much lower concentrations; undergoes subsequent conjugation with glucuronic acid.

Elimination Route

Excreted mainly as metabolites in urine (80%) and in feces (<17%).

Half-life

Extensive metabolizers: about 5 hours.

Poor metabolizers: about 22 hours.

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).

Actions

• Mechanism of action in the management of ADHD appears to be related to selective inhibition of the presynaptic norepinephrine transporter.

• Minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors.

• Not considered a stimulant.

Advice to Patients

• Provide patient or caregiver with a copy of the manufacturer’s patient information (medication guide); discuss and answer questions about its contents as needed. Instruct patient or caregiver to read and understand contents of medication guide before initiating therapy and each time the prescription is refilled.

• Risk of suicidal thinking. Importance of daily observation by family members and caregivers and of close communication with clinician. Importance of immediately informing clinician if clinical worsening, anxiety, agitation, panic attacks, insomnia, irritability, aggressive behaviors, hostility, impulsivity, restlessness, mania, depression, suicidal ideation or behaviors, or unusual changes in behavior occur, particularly during the first few months after initiation of therapy or following dosage adjustments.

• Hepatic dysfunction may rarely develop. Importance of informing clinician immediately if symptoms of hepatic injury (e.g., pruritus, jaundice, dark urine, upper right-sided abdominal tenderness, unexplained flu-like symptoms) occur.

• Importance of informing clinician immediately if adverse cardiovascular effects (e.g., chest pain, shortness of breath, fainting) occur.

• Importance of informing clinician immediately if precipitation of psychotic (e.g., hallucinations, delusional thinking) or manic symptoms occurs.

• Potential for drug to impair patient’s ability to perform potentially hazardous activities; use caution when driving or operating machinery until the effects of the drug on the individual are known.

• Risk of priapism. Importance of seeking immediate medical attention if erection persists for >4 hours.

• Importance of taking atomoxetine exactly as prescribed. (See Oral Administration under Dosage and Administration.)

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of advising patient or caregiver that the drug is an ocular irritant and that the capsules should not be opened; if eye contact occurs, flush affected eye(s) with water immediately, obtain medical advice, and wash hands and potentially contaminated surfaces as soon as possible.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and herbal products, as well as any concomitant illnesses/conditions (e.g., glaucoma, suicidal ideation or behaviors, cardiac/cardiovascular disease, mental/psychiatric disorder, hepatic disease).

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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