(AT oh mox e teen)
- Atomoxetine Hydrochloride
- Methylphenoxy-Benzene Propanamine
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Strattera: 10 mg, 18 mg, 25 mg, 40 mg, 60 mg
Strattera: 80 mg, 100 mg [contains fd&c blue #2 (indigotine)]
Brand Names: U.S.
- Norepinephrine Reuptake Inhibitor, Selective
Selectively inhibits the reuptake of norepinephrine (Ki 4.5 nM) with little to no activity at the other neuronal reuptake pumps or receptor sites.
Vd: IV: 0.85 L/kg
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
Urine (80%, as conjugated 4-hydroxy metabolite; <3% is excreted unchanged); feces (17%)
Time to Peak
Plasma: 1-2 hours; delayed 3 hours by high-fat meal
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)
98%, primarily albumin
Special Populations: Renal Function Impairment
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.
Special Populations: Hepatic Function Impairment
AUC is increased in extensive metabolizers with moderate or severe hepatic impairment.
Use: Labeled Indications
Attention-deficit/hyperactivity disorder: Treatment of attention-deficit/hyperactivity disorder (ADHD)
Hypersensitivity to atomoxetine or any component of the formulation; use with or within 14 days of MAO inhibitors; narrow-angle glaucoma; current or past 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 ).
Canadian labeling: Additional contraindications (not in U.S. labeling): Symptomatic cardiovascular diseases, moderate-to-severe hypertension; advanced arteriosclerosis; uncontrolled hyperthyroidism
Attention deficit hyperactivity disorder (ADHD) treatment: Oral: Note: Atomoxetine may be discontinued without the need for tapering dose.
Initial: 40 mg/day, increased after minimum of 3 days to ~80 mg/day; may administer as either a single daily dose or 2 evenly divided doses in morning and late afternoon/early evening. May increase to 100 mg/day in 2-4 additional weeks to achieve optimal response. Maximum daily dose: 100 mg/day.
Dosage adjustment in patients receiving strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or patients known to be CYP2D6 poor metabolizers: Initial: 40 mg/day; if tolerating therapy but inadequate response, may increase after minimum of 4 weeks to 80 mg/day.
Initial: 40 mg/day for 7-14 days (Step 1); if tolerated, may increase dose at 7-14 day intervals to 60 mg/day (Step 2) then to 80 mg/day (Step 3). If optimal response is not obtained after 2-4 additional weeks, may increase to a maximum dose of 100 mg/day.
Dosage adjustment in patients receiving strong CYP2D6 inhibitors: Initial: 40 mg/day; may increase to next dosage level after 14 days if previous dose is well tolerated but response is inadequate. Note: Canadian labeling does not include specific dosing recommendations in regards to patients who are poor CYP2D6 metabolizers although similar dose reductions would appear necessary.
Use has not been evaluated in the elderly.
ADHD treatment: Oral: Note: Atomoxetine may be discontinued without the need for tapering dose.
Children ≥6 years and ≤70 kg:
Initial: 0.5 mg/kg/day, increase after minimum of 3 days to ~1.2 mg/kg/day; may administer as either a single daily dose or 2 evenly divided doses in morning and late afternoon/early evening. Maximum daily dose: 1.4 mg/kg or 100 mg, whichever is less.
Dosage adjustment in patients receiving strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or patients known to be CYP2D6 poor metabolizers: Initial: 0.5 mg/kg/day; if tolerating therapy but inadequate response, may increase after minimum of 4 weeks to 1.2 mg/kg/day.
Initial: ~0.5 mg/kg/day for 7-14 days (Step 1); if tolerated, may increase to ~0.8 mg/kg/day for 7-14 days (Step 2), then to ~1.2 mg/kg/day (Step 3); re-evaluate after ≥30 days and adjust for response if necessary. Maximum daily dose: 1.4 mg/kg or 100 mg, whichever is less. Note: Children should weigh at least 20 kg at the time of initiation as 10 mg is the lowest available capsule strength and capsules are to be swallowed whole.
Dosing recommendations according to weight:
Initial (Step 1):
20-29 kg: 10 mg/day
30-44 kg: 18 mg/day
45-64 kg: 25 mg/day
65-70 kg: 40 mg/day
First titration (Step 2):
20-29 kg: 18 mg/day
30-44 kg: 25 mg/day
45-64 kg: 40 mg/day
65-70 kg: 60 mg/day
Second titration (Step 3):
20-29 kg: 25 mg/day
30-44 kg: 40 mg/day
45-64 kg: 60 mg/day
65-70 kg: 80 mg/day
Dosage adjustment in patients receiving strong CYP2D6 inhibitors: Initial: 0.5 mg/kg/day; may increase to next dosage level after 14 days if previous dose is well tolerated but response is inadequate. Note: Canadian labeling does not include specific dosing recommendations in regards to patients who are poor CYP2D6 metabolizers although similar dose reductions would appear necessary.
Children ≥6 years and >70 kg: Refer to adult dosing.
Dosing: Renal Impairment
No dosage adjustment necessary.
Dosing: Hepatic Impairment
Mild impairment (Child-Pugh class A): No dosage adjustment provided in manufacturer’s labeling.
Moderate impairment (Child-Pugh class B): All doses should be reduced to 50% of normal.
Severe impairment (Child-Pugh class C): All doses should be reduced to 25% of normal.
Administer with or without food as a single daily dose in the morning or as two evenly divided doses in morning and late afternoon/early evening. Swallow capsules whole; do not open capsules. If opened accidentally, do not touch eyes; wash hands immediately (product is an ocular irritant).
Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
Beta2-Agonists: AtoMOXetine may enhance the tachycardic effect of Beta2-Agonists. Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of AtoMOXetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Imatinib: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Iobenguane I 123: Antidepressants (Selective Norepinephrine Reuptake Inhibitor) may diminish the therapeutic effect of Iobenguane I 123. Avoid combination
MAO Inhibitors: May enhance the neurotoxic (central) effect of AtoMOXetine. Avoid combination
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Sympathomimetics: AtoMOXetine may enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Percentages as reported in children and adults; some adverse reactions may be increased in "poor metabolizers" (CYP2D6). Frequency not always defined.
Central nervous system: Headache (19%; children and adolescents), insomnia (1% to 19%), drowsiness (8% to 11%)
Dermatologic: Hyperhidrosis (4% to 15%)
Gastrointestinal: Xerostomia (17% to 35%), nausea (7% to 26%), decreased appetite (15% to 23%), abdominal pain (7% to 18%), vomiting (4% to 11%), constipation (1% to 11%)
Genitourinary: Erectile dysfunction (8% to 21%)
1% to 10%:
Cardiovascular: Increased diastolic blood pressure (5% to 9%; ≥15 mm Hg), systolic hypertension (4% to 5%), palpitations (3%), cold extremities (1% to 3%), syncope (≤3%), flushing (≥2%), orthostatic hypotension (≤2%), tachycardia (≤2%), prolonged Q-T interval on ECG
Central nervous system: Fatigue (6% to 10%), dizziness (5% to 8%), depression (4% to 7%), disturbed sleep (3% to 7%), irritability (5% to 6%), jitteriness (2% to 5%), abnormal dreams (4%), chills (3%), paresthesia (adults 3%; postmarketing observation in children), anxiety (≥2%), hostility (children and adolescents 2%), emotional lability (1% to 2%), agitation, restlessness, sensation of cold
Dermatologic: Excoriation (2% to 4%), skin rash (2%), pruritus, urticaria
Endocrine & metabolic: Weight loss (2% to 7%), decreased libido (3%), hot flash (3%), increased thirst (2%), menstrual disease
Gastrointestinal: Dyspepsia (4%), anorexia (3%), dysgeusia, flatulence
Genitourinary: Ejaculatory disorder (2% to 6%), urinary retention (1% to 6%), dysmenorrhea (3%), dysuria (2%), orgasm abnormal, pollakiuria, prostatitis, testicular pain, urinary frequency
Neuromuscular & skeletal: Tremor (1% to 5%), muscle spasm, weakness
Ophthalmic: Blurred vision (1% to 4%), conjunctivitis (1% to 3%), mydriasis
Respiratory: Pharyngolaryngeal pain
Miscellaneous: Therapeutic response unexpected (2%)
<1% (Limited to important or life-threatening): Cerebrovascular accident, delusions, growth suppression (children), hallucination, hepatotoxicity, hypersensitivity reaction, hypomania, impulsivity, mania, myocardial infarction, panic attack, pelvic pain, priapism, Raynaud's phenomenon, rhabdomyolysis, seizure (including patients with no prior history or known risk factors for seizure), severe hepatic disease, suicidal ideation, tics
Concerns related to adverse effects:
• Aggressive behavior: New or worsening symptoms of hostility or aggressive behaviors have been associated with atomoxetine, particularly with the initiation of therapy.
• Allergic reactions: Anaphylactic reactions, angioneurotic edema, urticaria, and rash may occur (rare).
• Altered cardiac conduction: In clinical trials, at therapeutic doses, atomoxetine consistently did not prolong the QT/QTc interval; however, one placebo-controlled study in healthy CYP2D6 poor metabolizers demonstrated a statistically significant increase in QTc with increasing atomoxetine concentrations (Loghin 2012; Martinez-Raga 2013). Case reports suggest that atomoxetine overdose may increase the QT interval; however, this occurred when atomoxetine was combined with other agents known to have QT prolongation potential or inhibit CYP2D6 (Barker 2004; Sawant 2004). Atomoxetine, at high concentrations ex vivo, has demonstrated hERG channel block (Scherer 2009).
• Cardiovascular events: Atomoxetine has been associated with serious cardiovascular events including sudden death in patients with preexisting structural cardiac abnormalities or other serious heart problems (sudden death in children and adolescents; sudden death, stroke, and MI in adults). Atomoxetine should be avoided in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that could increase the risk of sudden death that these conditions alone carry. Patients should be carefully evaluated for cardiac disease prior to initiation of therapy. Perform a prompt cardiac evaluation in patients who develop symptoms of exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during treatment.
• Hepatotoxicity: Use may be associated with rare but severe hepatotoxicity, including hepatic failure; discontinue and do not restart if signs or symptoms of hepatotoxic reaction (eg, jaundice, pruritus, flu-like symptoms, dark urine, right upper quadrant tenderness) or laboratory evidence of liver injury are noted. The majority of reported cases occurred within 120 days of initiation of therapy.
• Orthostasis: Orthostasis and subsequent syncope may occur. Use with caution in patients predisposed to hypotension, or with conditions associated with abrupt heart rate or blood pressure changes.
• Priapism: Prolonged and painful erections (priapism), sometimes requiring surgical intervention, have been reported (rarely) with methylphenidate and atomoxetine use in pediatric and adult patients. Priapism has been reported to develop after some time on the drug, often subsequent to an increase in dose but also during a period of drug withdrawal (drug holidays or discontinuation). Patients with certain hematological dyscrasias (eg, sickle cell disease), malignancies, perineal trauma, or concomitant use of alcohol, illicit drugs, or other medications associated with priapism may be at increased risk. Patients who develop abnormally sustained or frequent and painful erections should discontinue therapy and seek immediate medical attention. An emergent urological consultation should be obtained in severe cases. Priapism has been associated with different dosage forms and products; it is not known if rechallenge with a different formulation will risk recurrence. Avoidance of stimulants and atomoxetine may be preferred in patients with severe cases that were slow to resolve and/or required detumescence (Eiland, 2014).
• Psychiatric effects: Treatment-emergent psychotic or manic symptoms (eg, hallucinations, delusional thinking, mania) may occur in children and adolescents without a prior history of psychotic illness or mania. Consider discontinuation of treatment if symptoms occur.
• ADHD and comorbidities: Randomized, controlled trials have demonstrated that atomoxetine does not worsen anxiety in patients with existing anxiety disorders or tics related to Tourette’s disorder.
• Bipolar disorder: Use caution in patients with comorbid bipolar disorder; therapy may induce mixed/manic episodes. Atomoxetine is not approved for major depressive disorder; patients presenting with depressive symptoms should be screened for bipolar disorder.
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustments necessary in moderate and severe hepatic insufficiency.
• Hypertension: Use with caution in patients with hypertension and other cardiovascular or cerebrovascular conditions that might be exacerbated by increases in blood pressure or heart rate. CYP2D6 poor metabolizers may experience greater increases in blood pressure and heart rate effects.
• Urinary retention: Use with caution in patients with a history of urinary retention or bladder outlet obstruction; may cause urinary retention/hesitancy.
• CYP2D6 poor metabolizers: Dosage adjustments are recommended in CYP2D6 poor metabolizers; these patients have increased exposure to atomoxetine.
• Pediatric: [US. Boxed Warning]: Use with caution in pediatric patients; may be an increased risk of suicidal ideation. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. Growth should be monitored during treatment. Height and weight gain may be reduced during the first 9 to 12 months of treatment, but should recover by 3 years of therapy.
• ADHD treatment: Appropriate use: Recommended to be used as part of a comprehensive treatment program for attention deficit disorders.
Patient growth (weight/height gain in children); attention, hyperactivity, anxiety, worsening of aggressive behavior or hostility; blood pressure and pulse (baseline and following dose increases and periodically during treatment)
Family members and caregivers need to monitor patient daily for emergence of irritability, agitation, unusual changes in behavior, and suicide ideation. Pediatric patients should be monitored closely for suicidality, clinical worsening, or unusual changes in behavior, especially during the initial for months of therapy or at times of dose changes. Appearance of symptoms needs to be immediately reported to healthcare provider.
Thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Martinez-Raga, 2013; Vetter, 2008). Periodically reevaluate the long-term usefulness of the drug for the individual patient.
Pregnancy Risk Factor
Adverse events have been observed in animal reproduction studies. Information related to atomoxetine use in pregnancy is limited; appropriate contraception is recommended for sexually active women of childbearing potential (Heiligenstein, 2003).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience abdominal pain, insomnia, nausea, vomiting, lack of appetite, dry mouth, constipation, sexual dysfunction, loss of strength and energy, or fatigue. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), behavioral changes, irritability, agitation, panic attacks, hallucinations, tachycardia, abnormal heartbeat, severe headache, difficult urination, priapism, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), angina, shortness of breath, severe dizziness, or passing out (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
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Other brands: Strattera