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Pronunciation: A-toe-MOX-e-teen HYE-droe-KLOR-ide
Class: Psychotherapeutic agent
- Capsules, oral 10 mg
- Capsules, oral 18 mg
- Capsules, oral 25 mg
- Capsules, oral 40 mg
- Capsules, oral 60 mg
- Capsules, oral 80 mg
- Capsules, oral 100 mg
Selective inhibition of the presynaptic norepinephrine transporter is suspected.
C max is reached approximately 1 to 2 h after dosing. Rapidly absorbed with an absolute bioavailability of approximately 63% in extensive metabolizers and 94% in poor metabolizers. Administration with a high-fat meal decreased the rate of absorption (decreased C max by 37% [adults] and 9% [children] ) and delayed T max by 3 h (adults). May be administered with or without food.
Vd is 0.85 L/kg (IV dose) and 98% is protein bound, primarily to albumin.
Primarily metabolized by CYP2D6; CYP2C19 and other CYP-450 enzymes are involved to a lesser extent. Major metabolite is 4-hydroxyatomoxetine, which is equipotent to atomoxetine but circulates at much lower concentrations.
Cl is approximately 0.35 L/h/kg and half-life is 5.2 h for extensive metabolizers. Cl is approximately 0.03 L/h/kg and half-life is 21.6 h for poor metabolizers. More than 80% is excreted in the urine and less than 17% in the feces (as metabolite). Less than 3% is excreted as unchanged atomoxetine.
Special PopulationsRenal 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.Hepatic Function Impairment
AUC is increased in extensive metabolizers with moderate or severe hepatic impairment. Dosage adjustment is required.Elderly
Pharmacokinetics in elderly patients have not been evaluated.Children
Pharmacokinetics in children and adolescents are similar to those in adults.Gender
Pharmacokinetics are similar in men and women.Race
Does not affect atomoxetine pharmacokinetics, except poor metabolizing is more common in white patients.
Indications and Usage
Treatment of attention deficit hyperactivity disorder (ADHD).
Binge eating disorder; nocturnal enuresis; weight reduction in women with obesity.
Narrow-angle glaucoma; use with MAOIs or within 2 weeks after discontinuing an MAOI; pheochromocytoma or a history of pheochromocytoma; hypersensitivity to any component of the product.
Dosage and AdministrationAdults and Children (more than 70 kg)
PO Start with 40 mg/day and increase the dose after a minimum of 3 days to a target total daily dosage of approximately 80 mg. After 2 to 4 additional weeks, the dosage may be increased to a max of 100 mg/day in patients who have not achieved an optimal response. In patients receiving a strong CYP2D6 inhibitor (eg, fluoxetine), increase the 40 mg/day dosage to the target dosage of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dosage is well tolerated.Children (70 kg or less)
PO Start with 0.5 mg/kg/day and increase the dosage after a minimum of 3 days to a target total dosage of approximately 1.2 mg/kg/day (max, 1.4 mg/kg or 100 mg/day, whichever is less). In children receiving a strong CYP2D6 inhibitor (eg, fluoxetine) or known to be CYP2D6 poor metabolizers, increase the 0.5 mg/kg/day dosage to the target dosage of 1.2 mg/kg/day only if symptoms fail to improve after 4 weeks and the initial dosage is well tolerated.Hepatic Function Impairment
PO In patients with moderate hepatic impairment (Child-Pugh class B), reduce initial and target doses to 50% of the normal dose; in patients with severe hepatic impairment (Child-Pugh class C), reduce the initial dose and target dose to 25% of normal.
- Administer prescribed dose without regard to meals. Administer with food if GI upset occurs.
- May be administered as a single daily dose or as evenly divided doses in the morning and late afternoon or early evening.
- Can be discontinued without being tapered.
- Should be taken whole; capsules should not be opened.
Store between 59° and 86°F.
Use with caution; the CV effects of albuterol may be potentiated.CYP2D6 inhibitors (eg, fluoxetine, paroxetine, quinidine)
The AUC and peak plasma level of atomoxetine may be increased. Dosage adjustment may be necessary.CYP3A4 substrates (eg, midazolam)
Plasma concentrations may be increased by atomoxetine; however, dosage adjustments are not recommended.Iobenguane
Atomoxetine may reduce uptake and diagnostic efficacy of iobenguane. False-negative iobenguane imaging tests may result. Discontinue atomoxetine approximately 24 h prior to iobenguane administration.MAOIs (eg, isocarboxazid)
Coadministration is contraindicated. Do not administer atomoxetine within 2 weeks after discontinuing an MAOI and do not initiate treatment with an MAOI within 2 weeks after discontinuing atomoxetine.Pressor agents (eg, dobutamine, dopamine)
Possible increased BP. Use with caution.
Hot flush (8%); palpitations, syncope (3%); orthostatic hypotension, tachycardia (2%); QT prolongation, Raynaud phenomenon (postmarketing).
Headache (19%); insomnia (15%); somnolence (11%); fatigue (9%); depression (7%); dizziness, irritability (6%); tremor (5%); decreased libido (4%); paresthesia, sinus headache, sleep disorder (3%); feeling jittery, mood swings (2%); anxiety, hypoesthesia, lethargy, seizures, sensory disturbances, tics (postmarketing).
Hyperhidrosis (4%); rash (2%).
Conjunctivitis (3%); mydriasis (2%).
Dry mouth, nausea (21%); abdominal pain (18%); vomiting (11%); constipation (9%); dyspepsia (4%); anorexia (3%).
Erectile dysfunction (9%); urinary hesitancy and/or urinary retention (7%); dysmenorrhea (6%); delayed ejaculation and/or ejaculation disorder, dysuria (3%); menstruation irregularities (2%); male pelvic pain, priapism (postmarketing).
Appetite decreased (16%); weight decrease (7%).
Excoriation (4%); chills, unexpected therapeutic response (3%); early morning awakening (2%).
Atomoxetine increased the risk of suicidal thinking in short-term studies in children and adolescents. When considering the use of atomoxetine, balance the risk with clinical need. Observe children or adolescents closely for 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 prescriber. Atomoxetine is not approved for major depressive disorder.
Monitor patients closely for suicidality (suicidal thinking and behavior), clinical worsening, or unusual changes in behavior, especially during the initial few months of therapy or at times of dose changes. Monitor patients beginning therapy for the appearance or worsening of aggressive behavior or hostility. Monitor growth during treatment. Monitor pulse and BP at baseline, following dose increases, and periodically during therapy. Determine liver enzyme levels upon the first sign or symptom of liver dysfunction. Perform a careful history and physical exam to assess for the presence of cardiac disease. Conduct a prompt cardiac evaluation for patients who develop symptoms suggestive of cardiac disease during therapy.ADHD symptoms
Assess ADHD symptoms before and periodically throughout therapy.
Category C .
Safety and efficacy not established in children younger than 6 y.
Safety and efficacy have not been established.
Reactions, including angioneurotic edema, rash, and urticaria, can occur.
Dosage adjustment is recommended in patients with moderate to severe hepatic insufficiency.
Aggression or hostility
Aggressive behavior or hostility was observed more frequently among children and adolescents treated with atomoxetine compared with placebo.
Use with caution in patients with ADHD and comorbid bipolar disorder because of possible induction of a mixed/manic episode in patients at risk for bipolar disorder.
Sudden death has been associated with atomoxetine treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Sudden death, stroke, and MI have been reported in adults taking atomoxetine at usual doses for ADHD. In addition, because therapy can increase BP and heart rate, use with caution in patients with hypertension, tachycardia, or CV or cerebrovascular disease.
Poor CYP2D6 metabolizers have a 10-fold higher AUC and 5-fold higher C max to a given dose of atomoxetine compared with extensive metabolizers. The higher plasma levels in the poor metabolizers lead to a higher rate of some adverse reactions.
Monitor growth during treatment; mean weight and growth changes have been reported to be less than those occurring with placebo administration.
Rare cases of clinically significant liver injury have been reported during postmarketing use. Discontinue in patients with jaundice or laboratory evidence of liver injury; do not restart.
Use was associated with increased risk of mydriasis. Contraindicated in patients with narrow-angle glaucoma.
Peripheral vascular effects
Reports of new-onset and exacerbation of Raynaud phenomenon.
Elevated blood pressure and tachyarrhythmia have been reported in patients with pheochromocytoma taking atomoxetine. Use is contraindicated.
Painful and nonpainful penile erection lasting more than 4 h has been reported for adults and children receiving atomoxetine.
Psychotic or manic symptoms
Treatment-emergent psychotic or manic symptoms in children and adolescents without a history of psychotic illness or mania can occur.
Rate of occurrence of urinary retention and hesitancy may be increased.
Abnormal behavior; agitation; dizziness; GI symptoms; hyperactivity; mental changes, including disorientation and hallucinations; QT prolongation; somnolence; sympathetic nervous system activation (eg, blood pressure increased, dry mouth, mydriasis, tachycardia); tremor.
- Advise patient, family, or caregiver that the medication is started at a low dose and gradually increased as needed and tolerated.
- Advise patients, families, or caregivers that the medication should be taken as prescribed and not to stop taking or change the dose unless advised by their health care provider.
- Instruct patients that if they miss a dose, they should take it as soon as possible, but should not take more than the prescribed total daily amount in any 24-hour period.
- Advise patients, families, or caregivers to be alert for symptoms of aggressiveness, agitation, anxiety, depression, hostility, hypomania, insomnia, irritability, lack of impulse control, mania, panic attacks, psychomotor restlessness, suicidal thoughts, or other unusual changes in behavior, and to report such symptoms to their health care provider immediately.
- Advise patient, family, or caregiver that this drug is part of a total treatment program that should also include psychological, educational, and social interventions.
- Advise patient that drug may cause dizziness or other CNS disorders and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
- Advise patient that the drug may cause eye irritation if capsules are opened. If capsule content comes into contact with the eyes, flush eyes immediately with water and obtain medical advice. Wash hands and any potentially contaminated surfaces.
- Tell patients that the drug may be taken with or without food.
- Instruct patients that severe liver injury may develop while on therapy and to contact their health care provider if they develop dark urine, jaundice, right upper quadrant tenderness, or unexpected flu-like illness.
- Inform patients that rare cases of painful and nonpainful penile erection lasting more than 4 h have been reported and to contact their health care provider immediately if this occurs.
- Instruct patients to contact their health care provider if they are breast-feeding, pregnant, or thinking of becoming pregnant while taking this medication.
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