Description

Simple

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

Clinical

A stimulant used in the management of Attention Deficit Hyperactivity Disorder (ADHD).

Overview

Methylphenidate is a central nervous system stimulant used most commonly in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) and for narcolepsy. Also known as the marketed products Ritalin, Concerta, or Biphentin, methylphenidate is used with other treatment modalities (psychological, educational, cognitive behaviour therapy, etc) to improve the following group of developmentally inappropriate symptoms associated with ADHD: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. Long-acting formulations of psychostimulants such as methylphenidate, [DB01576], and [DB01255] are considered the most effective and widely used treatment for ADHD, and are considered first-line options for children, adolescents, and adults as recommended by CADDRA (Canadian ADHD Resource Alliance). [12] CADDRA recommends the use of methylphenidate due to long term studies, of over twenty years in duration, which show methylphenidate is safe and effective.

While its exact mechanism is unclear, methylphenidate (MPH) has been shown to act as a norepinephrine and dopamine reuptake inhibitor (NDRI), thereby increasing the presence of these neurotransmitters in the extraneuronal space and prolonging their action.[Read more

Pharmacology

Indication

Methylphenidate is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older and for the treatment of narcolepsy.

Pharmacodynamic

Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer. Radioligand binding studies demonstrate that binding of methylphenidate in the brain is localized to dopamine-rich areas, in particular in the prefrontal cortex wh... Read more

Mechanism of action

While its exact mechanism is unclear, methylphenidate (MPH) has been shown to act as a norepinephrine and dopamine reuptake inhibitor (NDRI), thereby increasing the presence of these neurotransmitters in the extraneuronal space and prolonging their action.[ Read more

Absorption

Concerta®: Methylphenidate is readily absorbed. Following oral administration of Concerta, plasma methylhphenidate concentrations reach an initial maximum at about 1 hour followed by gradual ascending concentrations over the next 5-9 hours. Mean times to reach peak plasma concentrations across all d... Read more

Protein binding

Concerta: In humans, 15 ± 5% of methylphenidate in the blood is bound to plasma proteins. [15]

Biphentin: In blood, methylphenidate and its metabolites are distributed between plasma (57%) and
erythrocyte... Read more

Volume of distribution

Concerta: Plasma methylphenidate concentrations in adults decline bi-exponentiallyfollowing oral administration.[15]Biphentin: The apparent distribution volume of methylphenidate in children is approximately... Read more

Clearance

The apparent mean systemic clearance after an oral dose is 10.2 and 10.5 L/h/kg in children and adults, respectively for a 0.3 mg/kg dose, and 0.565 L/h/kg after an intravenous dose of the racemate in healthy adult volunteers.[ Read more

Half life

Concerta: The half-life of methylphenidate in adults following oral administration of Concerta® was approximately 3.5 h.[15]

Biphentin: Methylphenidate is eliminated from plasma with a mean half-life of 2.... Read more

Route of elimination

After oral administration of an immediate release formulation of methylphenidate, 78%-97% of the dose is excreted in the urine and 1%-3% in the feces in the form of metabolites within 48-96 hours. Only small quantities ( Read more

Toxicity

Symptoms of overdose include vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, and d... Read more

Adverse Effects

Contraindications

  • Dose Form:
    • Capsule, extended release
    • Capsule, film coated, extended release
  • Time Period: Contraindicated during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following discontinuation of treatment with a monoamine oxidase inhibitor (hypertensive crises may result).
  • Regions: US
  • With Categories Coadmin:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: Canada
  • Patient Conditions:
      • Name: Pheochromocytoma
      • Drugbank Id: DBCOND0002904
  • Regions: Canada
  • Patient Conditions:
      • Name: Moderate to Severe Hypertension
      • Drugbank Id: DBCOND0042937
  • Regions: Canada
  • Patient Conditions:
      • Name: Symptomatic cardiovascular disease
      • Drugbank Id: DBCOND0107487
      • Modification Of:
        • Base:
          • Name: Cardiovascular Disease
          • Drugbank Id: DBCOND0028376
        • Severity:
          • Includes:
            • symptomatic
  • Regions: Canada
  • Patient Conditions:
      • Name: Advanced arteriosclerosis
      • Drugbank Id: DBCOND0107486
  • Regions: Canada
  • Patient Conditions:
      • Name: Thyrotoxicosis
      • Drugbank Id: DBCOND0021770
  • Dose Form:
    • extended release
    • chewable tablets
    • oral solution
    • transdermal patch
  • Regions: US
  • Patient Conditions:
      • Name: Motor tics
      • Drugbank Id: DBCOND0107725
  • Dose Form:
    • extended release
    • chewable tablets
    • oral solution
    • transdermal patch
  • Regions: US
  • Patient Conditions:
      • Name: Family history of Tourette's syndrome
      • Drugbank Id: DBCOND0107726
  • Dose Form:
    • extended release
    • chewable tablets
    • oral solution
    • transdermal patch
  • Regions: US
  • Patient Conditions:
      • Name: Tourette's Syndrome
      • Drugbank Id: DBCOND0028246
  • Regions: US
  • Patient Conditions:
      • Name: Anxiety
      • Drugbank Id: DBCOND0018828
  • Hypersensitivity:
    • methylphenidate
  • Regions: US
  • Regions: US
  • Patient Conditions:
      • Name: Tension
      • Drugbank Id: DBCOND0018825
  • Regions: US
  • Patient Conditions:
      • Name: Agitation
      • Drugbank Id: DBCOND0017779
  • Regions: US
  • Patient Conditions:
      • Name: Glaucoma
      • Drugbank Id: DBCOND0010013

Food Interactions

  • Avoid alcohol. Co-administration with alcohol may cause a "dose-dumping" effect with some extended-release formulations of methylphenidate. It may also potentiate the CNS effects of methylphenidate.
  • Take with or without food. Patients may take methylphenidate with food to alleviate GI upset.

Interactions

Type in a drug name to check for interaction with Methylphenidate
Type a drug name in the box above to get started
  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Methylphenidate.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Methylphenidate.
1-benzylimidazole
The risk or severity of hypertension can be increased when Methylphenidate is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of hypertension can be increased when Methylphenidate is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of hypertension can be increased when Methylphenidate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,5-Dinitrocatechol
The risk or severity of adverse effects can be increased when Methylphenidate is combined with 3,5-Dinitrocatechol.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of hypertension can be increased when Methylphenidate is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Methylphenidate.
4-Methoxyamphetamine
The risk or severity of hypertension can be increased when Methylphenidate is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of hypertension can be increased when Methylphenidate is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole
The therapeutic efficacy of 7-Nitroindazole can be decreased when used in combination with Methylphenidate.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypertensive activities of Methylphenidate.
Abacavir
Methylphenidate may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abediterol
The risk or severity of hypertension can be increased when Methylphenidate is combined with Abediterol.
Acarbose
Acarbose may decrease the excretion rate of Methylphenidate which could result in a higher serum level.
Acebutolol
Methylphenidate may decrease the antihypertensive activities of Acebutolol.
Aceclofenac
Aceclofenac may decrease the excretion rate of Methylphenidate which could result in a higher serum level.
Acemetacin
Acemetacin may decrease the excretion rate of Methylphenidate which could result in a higher serum level.
Acenocoumarol
The metabolism of Acenocoumarol can be decreased when combined with Methylphenidate.
Acepromazine
The risk or severity of adverse effects can be increased when Acepromazine is combined with Methylphenidate.
17 References
  1. 1 . Keating GM, McClellan K, Jarvis B: Methylphenidate (OROS formulation). CNS Drugs. 2001;15(6):495-500; discussion 501-3.PubMed: 11524026
  2. 2 . Markowitz JS, DeVane CL, Pestreich LK, Patrick KS, Muniz R: A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study. J Child Adolesc Psychopharmacol. 2006 Dec;16(6):687-98.PubMed: 17201613
  3. 3 . Fone KC, Nutt DJ: Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder. Curr Opin Pharmacol. 2005 Feb;5(1):87-93.PubMed: 15661631
  4. 4 . Sharma RP, Javaid JI, Pandey GN, Easton M, Davis JM: Pharmacological effects of methylphenidate on plasma homovanillic acid and growth hormone. Psychiatry Res. 1990 Apr;32(1):9-17.PubMed: 2190251
  5. 5 . Hodgkins P, Shaw M, Coghill D, Hechtman L: Amfetamine and methylphenidate medications for attention-deficit/hyperactivity disorder: complementary treatment options. Eur Child Adolesc Psychiatry. 2012 Sep;21(9):477-92. doi: 10.1007/s00787-012-0286-5. Epub 2012 Jul 5.PubMed: 22763750
  6. 6 . Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, Hamilton C, Spencer RC: Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry. 2006 Nov 15;60(10):1111-20. doi: 10.1016/j.biopsych.2006.04.022. Epub 2006 Jun 23.PubMed: 16806100
  7. 7 . Solanto MV: Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res. 1998 Jul;94(1):127-52.PubMed: 9708845
  8. 8 . Brennan AR, Arnsten AF: Neuronal mechanisms underlying attention deficit hyperactivity disorder: the influence of arousal on prefrontal cortical function. Ann N Y Acad Sci. 2008;1129:236-45. doi: 10.1196/annals.1417.007.PubMed: 18591484
  9. 9 . Berridge CW, Shumsky JS, Andrzejewski ME, McGaughy JA, Spencer RC, Devilbiss DM, Waterhouse BD: Differential sensitivity to psychostimulants across prefrontal cognitive tasks: differential involvement of noradrenergic alpha(1) - and alpha(2)-receptors. Biol Psychiatry. 2012 Mar 1;71(5):467-73. doi: 10.1016/j.biopsych.2011.07.022. Epub 2011 Sep 3.PubMed: 21890109
  10. 10 . Calipari ES, Ferris MJ, Salahpour A, Caron MG, Jones SR: Methylphenidate amplifies the potency and reinforcing effects of amphetamines by increasing dopamine transporter expression. Nat Commun. 2013;4:2720. doi: 10.1038/ncomms3720.PubMed: 24193139
  11. 11 . 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
  12. 12 . CADDRA - Canadian ADHD Practice Guidelines Link
  13. 13 . Concerta FDA label Link
  14. 14 . FDA Approved Drug Products: Daytrana® transdermal system Link
  15. 15 . Health Canada Label - Concerta File
  16. 16 . Health Canada Label - Biphentin File
  17. 17 . Health Canada - Ritalin File