Description

Simple

A medication used to manage Attention Deficit Hyperactivity Disorder (ADHD) by improving the ability to pay attention and control impulses.

Clinical

A selective norepinephrine reuptake inhibitor (SNRI) used in the management of Attention Deficit Hyperactivity Disorder (ADHD).

Overview

Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor used for the treatment of attention deficit hyperactivity disorder (ADHD). Also known as the marketed product Strattera, atomoxetine is used with other treatment modalities (psychological, educational, cognitive behaviour therapy, etc) to improve developmentally inappropriate symptoms associated with ADHD including distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. Although the underlying pathophysiology that causes ADHD remains unclear, evidence suggests that dysregulation in noradrenergic and dopaminergic pathways plays a critical role in suboptimal executive functioning within prefrontal regions of the brain, which are involved in attention and memory.[5] Atomoxetine has been shown to specifically increase NA and DA within the prefrontal cortex, but not in the nucleus accumbens (NA) or striatum.[Read more

Pharmacology

Indication

Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults.

Pharmacodynamic

Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor used for the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine has been shown to specifically increase norepinephrine and dopamine within the prefrontal cortex, which results in improved ADHD symptoms.[ Read more

Mechanism of action

Atomoxetine is known to be a potent and selective inhibitor of the norepinephrine transporter (NET),[ Read more

Absorption

The pharmacokinetic profile of atomoxetine is highly dependent on cytochrome P450 2D6 genetic polymorphisms of the individual.[ Read more

Protein binding

At therapeutic concentrations, 98.7% of plasma atomoxetine is bound to protein, with 97.5% of that being bound to albumin, followed by alpha-1-acid glycoprotein and immunoglobulin G.[ Read more

Volume of distribution

The reported volume of distribution of oral atomoxetine was 1.6-2.6 L/kg. The steady-state volume of distribution of intravenous atomoxetine was approximately 0.85 L/kg.[ Read more

Clearance

The clearance rate of atomoxetine depends the CYP2D6 genetic polymorphisms of the individual and can range of 0.27-0.67 L.h/kg.[ Read more

Half life

The reported half-life depends on the CYP2D6 genetic polymorphisms of the individual and can range from 3 to 5.6 hours.[ Read more

Route of elimination

Atomoxetine is excreted primarily as 4-hydroxyatomoxetine-O-glucuronide, mainly in the urine (greater than 80% of the dose) and to a lesser extent in the feces (less than 17% of the dose). Only a small fraction (less than 3%) of the atomoxetine dose is excreted as unchanged atomoxetine, indicating e... Read more

Toxicity

There is limited clinical trial experience with atomoxetine overdose. During postmarketing, there have been fatalities reported involving a mixed ingestion overdose of atomoxetine capsules and at least one other drug. There have been no reports of death involving overdose of atomoxetine capsules alo... Read more

Adverse Effects

Contraindications

  • Regions: Canada
  • Patient Conditions:
      • Name: Advanced arteriosclerosis
      • Drugbank Id: DBCOND0107486
  • Regions: Canada
  • Patient Conditions:
      • Name: Moderate to Severe Hypertension
      • Drugbank Id: DBCOND0042937
  • Regions: Canada
  • Patient Conditions:
      • Name: Hyperthyroidism
      • Drugbank Id: DBCOND0009048
  • Route:
    • Oral
  • Dose Form:
    • Capsule
  • Hypersensitivity:
    • true
  • Regions: US
  • Regions: US
  • Patient Conditions:
      • Name: Narrow angle glaucoma
      • Drugbank Id: DBCOND0104923
  • Regions: US
  • Patient Conditions:
      • Name: Pheochromocytoma
      • Drugbank Id: DBCOND0002904
  • Regions: US
  • Patient Conditions:
      • Name: Severe cardiovascular disorders
      • Drugbank Id: DBCOND0107565
      • Modification Of:
        • Base:
          • Name: Cardiovascular Disorders
          • Drugbank Id: DBCOND0055730
        • Severity:
          • Includes:
            • severe
  • Regions: US
  • With Categories:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996

Food Interactions

  • Take with or without food.

Interactions

Type in a drug name to check for interaction with Atomoxetine
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Atomoxetine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1-benzylimidazole
The risk or severity of hypertension can be increased when Atomoxetine is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of hypertension can be increased when Atomoxetine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of hypertension can be increased when Atomoxetine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of hypertension can be increased when Atomoxetine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Atomoxetine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Atomoxetine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Atomoxetine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Atomoxetine.
Abacavir
Atomoxetine may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abatacept
The metabolism of Atomoxetine can be increased when combined with Abatacept.
Abediterol
Atomoxetine may increase the tachycardic activities of Abediterol.
Abexinostat
The risk or severity of QTc prolongation can be increased when Atomoxetine is combined with Abexinostat.
Abiraterone
The metabolism of Atomoxetine can be decreased when combined with Abiraterone.
Acarbose
Acarbose may decrease the excretion rate of Atomoxetine which could result in a higher serum level.
Acebutolol
The metabolism of Atomoxetine can be decreased when combined with Acebutolol.
Aceclofenac
Aceclofenac may decrease the excretion rate of Atomoxetine which could result in a higher serum level.
Acemetacin
Acemetacin may decrease the excretion rate of Atomoxetine which could result in a higher serum level.
Acepromazine
The risk or severity of adverse effects can be increased when Atomoxetine is combined with Acepromazine.
Aceprometazine
The risk or severity of QTc prolongation can be increased when Atomoxetine is combined with Aceprometazine.
18 References
  1. 1 . Yu G, Li GF, Markowitz JS: Atomoxetine: A Review of Its Pharmacokinetics and Pharmacogenomics Relative to Drug Disposition. J Child Adolesc Psychopharmacol. 2016 May;26(4):314-26. doi: 10.1089/cap.2015.0137. Epub 2016 Feb 9.PubMed: 26859445
  2. 2 . Hutchison SL, Ghuman JK, Ghuman HS, Karpov I, Schuster JM: Efficacy of atomoxetine in the treatment of attention-deficit hyperactivity disorder in patients with common comorbidities in children, adolescents and adults: a review. Ther Adv Psychopharmacol. 2016 Oct;6(5):317-334. doi: 10.1177/2045125316647686. Epub 2016 May 20.PubMed: 27721971
  3. 3 . Aman MG, Smith T, Arnold LE, Corbett-Dick P, Tumuluru R, Hollway JA, Hyman SL, Mendoza-Burcham M, Pan X, Mruzek DW, Lecavalier L, Levato L, Silverman LB, Handen B: A review of atomoxetine effects in young people with developmental disabilities. Res Dev Disabil. 2014 Jun;35(6):1412-24. doi: 10.1016/j.ridd.2014.03.006. Epub 2014 Apr 16.PubMed: 24732041
  4. 4 . Kratochvil CJ, Heiligenstein JH, Dittmann R, Spencer TJ, Biederman J, Wernicke J, Newcorn JH, Casat C, Milton D, Michelson D: Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry. 2002 Jul;41(7):776-84. doi: 10.1097/00004583-200207000-00008.PubMed: 12108801
  5. 5 . Del Campo N, Chamberlain SR, Sahakian BJ, Robbins TW: The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2011 Jun 15;69(12):e145-57. doi: 10.1016/j.biopsych.2011.02.036. Epub 2011 May 6.PubMed: 21550021
  6. 6 . Marshall CA, Brodnik ZD, Mortensen OV, Reith MEA, Shumsky JS, Waterhouse BD, Espana RA, Kortagere S: Selective activation of Dopamine D3 receptors and norepinephrine transporter blockade enhances sustained attention. Neuropharmacology. 2019 Apr;148:178-188. doi: 10.1016/j.neuropharm.2019.01.003. Epub 2019 Jan 8.PubMed: 30633928
  7. 7 . Verbeeck W, Bekkering GE, Van den Noortgate W, Kramers C: Bupropion for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2017 Oct 2;10:CD009504. doi: 10.1002/14651858.CD009504.pub2.PubMed: 28965364
  8. 8 . Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW: Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002 Nov;27(5):699-711.PubMed: 12431845
  9. 9 . Ding YS, Naganawa M, Gallezot JD, Nabulsi N, Lin SF, Ropchan J, Weinzimmer D, McCarthy TJ, Carson RE, Huang Y, Laruelle M: Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD. Neuroimage. 2014 Feb 1;86:164-71. doi: 10.1016/j.neuroimage.2013.08.001. Epub 2013 Aug 9.PubMed: 23933039
  10. 10 . Ludolph AG, Udvardi PT, Schaz U, Henes C, Adolph O, Weigt HU, Fegert JM, Boeckers TM, Fohr KJ: Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations. Br J Pharmacol. 2010 May;160(2):283-91. doi: 10.1111/j.1476-5381.2010.00707.x.PubMed: 20423340
  11. 11 . Coleman J., Cox A. and Cowley N. (2011). Side Effects of Drugs Annual. Elsevier.
  12. 12 . Waller D., and Sampson A. (2018). Medical Pharmacology and Therapeutics (5th ed.). Elsevier.
  13. 13 . Kolevzon A. (2013). The neuroscience of autism spectrum disorders. Elsevier.
  14. 14 . FDA approvals Link
  15. 15 . NIH Link
  16. 16 . CADDRA - Canadian ADHD Practice Guidelines Link
  17. 17 . FDA Approved Drug Products: Strattera (atomoxetine) oral capsules Link
  18. 18 . FDA Label - atomoxetine File