atomoxetine

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 98%.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP2D6 isoenzyme pathway; the CYP2D6 enzyme system exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↑ atomoxetine concentrations and an ↑ risk of adverse effects).

Half-Life: 5 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 hr	12–24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent or within 2 wk of therapy with MAO inhibitors;
Angle-closure glaucoma;
Pheochromocytoma;
Hypertension, tachycardia, cardiovascular, or cerebrovascular disease.

Use Cautiously in:

Personal or family history of bipolar disorder, mania, or hypomania;
Concurrent albuterol or vasopressors (↑ risk of adverse cardiovascular reactions);
CYP2D6 poor metabolizers (↓ dose);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Safety not established in breastfeeding;
May ↑ risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children or adolescents
;
Pedi: Children <6 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, orthostatic hypotension, QT interval prolongation, syncope, tachycardia

Derm: ↑sweating, rash, urticaria

GI: nausea, vomiting, dyspepsia, HEPATOTOXICITY, Adultsconstipation, dry mouth

GU: Adultsdysmenorrhea, ejaculatory problems, erectile dysfunction, libido changes, priapism, urinary hesitation, urinary retention

Metab: ↓appetite, ↓growth, weight loss

MS: RHABDOMYOLYSIS

Neuro: dizziness, fatigue, insomnia, mood swings, aggression, behavioral disturbances, delusions, hallucinations, hostility, mania, paresthesia, SUICIDAL THOUGHTS, thought disorder

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors may result in serious, potentially fatal reactions; concurrent use within 2 wk of each other contraindicated.
↑risk of cardiovascular effects with albuterol or vasopressors; use cautiously.
CYP2D6 inhibitors, including quinidine, fluoxetine, or paroxetine, may ↑ levels and risk of toxicity; dose ↓ recommended.

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥6 yr and >70 kg): 40 mg/day initially; may ↑ every 3 days to a daily target dose of 80 mg/day given as a single dose in the morning or evenly divided doses in the morning and late afternoon/early evening; may further ↑ after 2–4 wk up to 100 mg/day. Concurrent use of CYP2D6 inhibitor (quinidine, fluoxetine, paroxetine): 40 mg/day initially; may ↑ if needed to 80 mg/day after 4 wk.
PO (Children ≥6 yr and ≤70 kg): 0.5 mg/kg/day initially; may ↑ every 3 days to a daily target dose of 1.2 mg/kg, given as a single dose in the morning or evenly divided doses in the morning and late afternoon/early evening (not to exceed 1.4 mg/kg/day or 100 mg/day, whichever is less). Concurrent use of CYP2D6 inhibitor (quinidine, fluoxetine, paroxetine) or CYP2D6 poor metabolizer: 0.5 mg/kg/day initially; may ↑ if needed to 1.2 mg/kg/day after 4 wk.

Hepatic Impairment

PO (Adults and Children ): Moderate hepatic impairment:↓ initial and target dose by 50%; Severe hepatic impairment:↓ initial and target dose to 25% of normal.

Availability ⬆ ⬇

(Generic available)

Capsules: 10 mg; 18 mg; 25 mg; 40 mg; 60 mg; 80 mg; 100 mg

Assessment ⬆ ⬇

Assess attention span, impulse control, and interactions with others.
Assess for bipolar disorder (screen patients for a personal or family history of bipolar disorder, mania, or hypomania) before starting therapy.
Monitor BP and HR periodically during therapy. Obtain a history (including assessment of family history of sudden death or ventricular arrhythmia), physical exam to assess for cardiac disease, and further evaluation (ECG and echocardiogram), if indicated. If exertional chest pain, unexplained syncope, or other cardiac symptoms occur, evaluate promptly.
Monitor growth, body height, and weight in children.
Assess for signs of liver injury (pruritus, dark urine, jaundice, right upper quadrant tenderness, unexplained flu-like symptoms) during therapy. Discontinue and do not restart atomoxetine in patients with jaundice or laboratory evidence of liver injury.
Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression. Psychotic or manic symptoms (hallucinations, delusional thinking, mania) in patients without a history of psychotic illness or mania can be caused by atomoxetine at usual doses. If symptoms occur, consider discontinuing therapy.

Lab Test Considerations:

Monitor liver enzymes (at signs/symptoms of liver dysfunction and for several wk after discontinuation).
In normal, intermediate, and ultrarapid CYP2D6 metabolizers or in patients with unknown CYP2D6 metabolizer status, draw peak plasma concentrations 1–2 hr after dose. In intermediate CYP2D6 metabolizers, consider drawing peak plasma concentrations 2–4 hr after dose in patients with lower enzyme activity or if the *10 allele is present. For poor CYP2D6 metabolizers, draw peak plasma concentrations 4 hr after dose. Therapeutic reference range: 200–1000 ng/mL.Laboratory alert level: 2000 ng/mL.

Implementation ⬆ ⬇

Do not confuse atomoxetine with atorvastatin.
PO: Administer without regard to food. Doses may be discontinued without tapering. DNC: Swallow capsules whole; do not open, crush, or chew.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient/caregiver to read Patient Information before starting therapy. Instruct patient to take medication as directed. Take missed doses as soon as possible, but should not take more than the total daily amount in any 24-hr period.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Inform patient that sharing this medication may be dangerous.
Advise patient and/or caregiver to notify health care provider if thoughts about suicide or dying, attempts to commit suicide, new or worse depression, new or worse anxiety, feeling very agitated or restless, panic attacks, trouble sleeping, new or worse irritability, acting aggressive or hostile, being angry or violent, acting on dangerous impulses, an extreme ↑ in activity and talking, or other unusual changes in behavior or mood occur or if signs and symptoms of severe liver injury (pruritus, dark urine, jaundice, right upper quadrant tenderness, unexplained flu-like symptoms) occur.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Register patients who took atomoxetine during pregnancy in Pregnancy Exposure Registry to monitor pregnancy outcomes by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇