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Amphetamine

Tejus Pradeep, Lindsay Rothenberg Standeven, M.D.

DRUG CLASS

  • CNS stimulant[1]

INDICATIONS

FDA

NON-FDA APPROVED USES

  • Depression in medically ill older adults or adult patients with terminal illness and/or receiving palliative care
  • Fatigue, cancer-related

MECHANISM

  • Increases intrasynaptic concentrations of NE and DA through reuptake inhibition

FORMS

brand name

generic

manufacturer

route

form

dosage^

cost*

Adderall

Amphetamine

DSM Pharmaceuticals Inc

PO

Tablet

2.5-40 mg

5 mg (100): $622.00

*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

ADULT DOSING

USUAL

Adderall IR

  • Starting dose is 2.5 mg twice daily, or 5 mg once a day[1]
  • Increase dosage by 5 mg/wk until therapeutic range is reached. Maximum dosage is 40 mg/day[1]

Adderall XR

  • Initial dosing at 10-20mg every morning. Maximum dosage is 40 mg/day

GERIATRIC

  • Amphetamines like Adderall have not been studied in the geriatric population[1]

RENAL

  • Renal dysfunction can hinder elimination of amphetamine[1]

HEPATIC

  • Hepatic insufficiency can hinder elimination of amphetamine[1]

PREGNANCY

  • Pregnancy Category C[1]

BREASTFEEDING

  • Amphetamine is excreted in breast milk[1]
  • It is not advised to take the drug while breastfeeding[1]

PEDIATRIC DOSING

USUAL

  • Children 3-5 yrs: starting dose is 2.5 mg in the morning[1]
  • Children over 6 yrs: starting dose is 2.5 mg twice daily, or 5 mg once a day[1]

RENAL

  • Renal dysfunction can hinder elimination of amphetamine[1]

ADVERSE DRUG REACTIONS

GENERAL

  • Appetite suppression, weight loss, transient sleep disturbances, abdominal pain, headaches[1]

COMMON

  • Headaches, dizziness, nausea, stomach pain, reduced appetite, weight loss

OCCASIONAL

  • Urticaria, hypersensitivity reactions, insomnia, euphoria, dysphoria, tremor[1]

RARE

  • Hypertension, tics, mania, hallucinations, aggression, anxiety, dyphoria
  • Blackbox warning: sudden death due to cardiac problems exacerbated by psychiatric drugs

DRUG INTERACTIONS

Drug-to-Drug Interactions

Drug

Effect of Interaction

Recommendations/Comments

Antacids

May increase effect of stimulants

Monitor therapy

Atomoxetine

May increase effect of stimulants

Monitor therapy

Cannabinoids

May increase effect of stimulants

Monitor therapy

Linezolid

May increase effect of stimulants

Monitor therapy

MAO Inhibitors

May increase effect of stimulants

Monitor therapy

Proton Pump Inhibitors

May increase effect of stimulants

Monitor therapy

TCAs

May increase effect of stimulants

Monitor therapy

Antipsychotics

May decrease effect of stimulants

Monitor therapy

Ascorbic Acid

May decrease effect of stimulants

Monitor therapy

Lithium

May decrease effect of stimulants

Monitor therapy

Multivitamins

May decrease effect of stimulants

Monitor therapy

Opioids

Stimulants may increase effect of opioids

Monitor therapy

Sympathomimetics

Stimulants may increase effect of sympathomimetics

Monitor therapy

PHARMACOKINETIC

Absorption

  • Immediate release: rapid absorption
  • Extended release: rapid absorption

Protein Binding

  • 16%

Bioavailability

  • The pH of GI system impacts bioavailability of amphetamine; it is well absorbed in the gut
  • Exact bioavailability not established

Distribution

  • 6 L/kg

New heading

  • D-amphetamine: 5 hours[2]
  • L-amphetamine: 5.25 hours[2]

Metabolism

  • Hepatic metabolism via CYP2D6 enzyme

Elimination

  • Primarily eliminated in urine

Half Life

  • Immediate release: 9 hours
  • Extended release: 10-13 hours

COMMENTS

  • The FDA classifies Adderall as a Schedule II controlled substance[1]
  • Amphetamines are frequently abused and are established to cause dependence[1]
  • In case of overdose, contact Poison Control Center immediately[1]
  • The FDA estimates approximately 3 kg of weight loss after the first year and 1 kg of weight loss after the second year of using amphetamines
  • Decision between short- and long-acting products should be based on patient’s daily behavioral routines
  • It is not necessary to taper when discontinuing stimulant use
  • It is recommended for patients to eat a high-fat meal in the evenings, as stimulant effects are lower at this time. This helps address nausea and appetite issues.
  • Use with caution in individuals with preexisting or possible: Bipolar disorder (possible induction of mixed/manic episode), preexisting psychotic disorder, tic or Tourette’s (exacerbate motor and phonic tics and Tourette’s syndrome) and substance use disorder. [1]

References

  1. Adderall (FDA Package Insert). DSM Pharmaceuticals Inc. Greenville, NC. 2007. Accessed: January 3, 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011522s040lbl.pdf
  2. Amphetamine. Drug Bank. Accessed: January 3, 2019. https://www.drugbank.ca/drugs/DB00182
  3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.). Washington, DC: American Psychiatric Association, 2000.
  4. Caballero J, Nahata MC. Atomoxetine hydrochloride for the treatment of attention-deficit/hyperactivity-disorder. Clin Ther. 2003; 25: 3065-83.
  5. Curatolo P, D’Agati E, Moavero R. The neurobiological basis of ADHD. Ital J Pediatr. 2010; 36: 79.
  6. Daughton JM, Kratochvil CJ. Review of ADHD pharmacotherapies: advantages, disadvantages, and clinical pearls. J Am Acad Child Adolsc Psychiatry. 2000; 48:240-8.
  7. Dopheide JA, Pliszka SR. Attention-deficit-hyperactivity-disorder: an update. Pharmacotherapy. 2009; 29: 656-79.
  8. Jain R, Segal S, Kollins SH, et al. Clonidine extended-release tablets for pediatric patients with attention-deficit/hyperactivity-disorder. J Am Acad Child Adolesc Psychiatry. 2011; 50: 171-9.
  9. LexiComp® Online. 2017. Accessed 23rd October 2016.
  10. Pediatric Pharmacotherapy. Chapter 30: Attention-Deficit/Hyperactivity Disorder. American College of Clinical Pharmacy. Lenexa, Kansas.
  11. Pliska S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivit-disorder. J Am Acad Child Adolsc Psychiatry. 2007; 46: 894-921.
  12. Sallee FR, Lyne A, Wigal T, et al. Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity-disorder. J Child Adolesc Psychopharmacol. 2009; 19: 215-26.
  13. Sallee FR, McGrough J, Wigal T, et al. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity-disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2009; 48: 155-65.
  14. Scahill L. Alpha-2 adrenergic agonists in children with inattention, hyperactivity, and impulsiveness. CNS Drugs. 2009; 23(suppl 1): 43-9.
  15. Stahl S. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 2nd ed. New York: Cambridge University Press, 2000.
  16. Tripp G, Wickens JR. Neurobiology of ADHD. Neuropharmacology. 2009; 57: 579-89.
  17. Valera EM, Faraone SV, Murray KE, et al. Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2010; 61: 1361-9.

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Last updated: January 3, 2019

Citation

Pradeep, Tejus, and Lindsay R Standeven. "Amphetamine." Johns Hopkins Psychiatry Guide, 2019. Johns Hopkins Guide, www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Psychiatry_Guide/787274/all/Amphetamine.
Pradeep T, Standeven LR. Amphetamine. Johns Hopkins Psychiatry Guide. 2019. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Psychiatry_Guide/787274/all/Amphetamine. Accessed March 19, 2019.
Pradeep, T., & Standeven, L. R. (2019). Amphetamine. In Johns Hopkins Psychiatry Guide. Available from https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Psychiatry_Guide/787274/all/Amphetamine
Pradeep T, Standeven LR. Amphetamine [Internet]. In: Johns Hopkins Psychiatry Guide. ; 2019. [cited 2019 March 19]. Available from: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Psychiatry_Guide/787274/all/Amphetamine.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Amphetamine ID - 787274 A1 - Pradeep,Tejus, AU - Standeven,Lindsay,M.D. Y1 - 2019/01/03/ BT - Johns Hopkins Psychiatry Guide UR - https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Psychiatry_Guide/787274/all/Amphetamine DB - Johns Hopkins Guide DP - Unbound Medicine ER -