Contents

Search

methylphenidate (Ritalin, Concerta, Daytrana, Metadate CD, Centedrine)

Tradename: Ritalin. (methylphenidate hydrochloride) DEA-controlled substance: class 2. Indications: - attention deficit hyperactivity disorder [17] - may improve classroom behavior in children with ADHD [22] - narcolepsy - depression [14] - apathy [20] - may improve cognition after traumatic brain injury in children [21] Contraindications: Caution: 1) hypertension 2) seizures & EEG abnormalities 3) high potential for abuse Dosage: 1) 5-10 mg PO BID/TID, generally 30-45 minutes before meals 2) average dose is 20-30 mg/day 3) sustained release (SR) administered BID 4) maximum dose: 60 mg/day 5) Concerta: QAM dosing; 18-36 mg PO QD a) 18 mg QD is comparable to 5 mg Ritalin TID b) dosage should be taken in the morning c) generics for Concerta may not be bioequivalent [16] 6) Metadate CD: QD dosing 7) Ritalin LA: start 20 mg QD; max 60 mg QD [9] 8) Daytrana patch: QD, patch worn 9 hours/day [11] Tabs: 5, 10, 20 mg. Ritalin LA: 20, 30 & 40 mg capsules. Concerta: 18 & 36 mg.* DEXmethylphenidate: - dextro isomer (may have fewer adverse effects) Daytrana patch [12] * 2 generic versions of Concerta continue to be available in June 2015 months after the FDA deemed them not therapeutically equivalent [16] * when switching methylphenidate products, discontinue existing treatment & titrate the new product using a titration schedule [22] Pharmacokinetics: 1) onset of action 2-5 days 2) t1/2 2-7 hours 3) patch: effects of 9 hour patch last 12 hours [11] Adverse effects: 1) common (> 10%) - tachycardia, anorexia, nervousness, insomnia 2) less common (1-10%) - hypersensitivity, dizziness, drowsiness, epigastric pain 3) uncommon (< 1%) - anemia, blurred vision, leukopenia, thrombocytopenia, convulsions, nausea/vomiting, hypertension, hypotension, palpitations, cardiac arrhythmias, movement disorders, precipitation of Tourette's syndrome, fever, headache, rash, growth retardation, weight loss 4) increased risk of cardiac arrhythmias (RR=1.6) [18] - highest risk 1-3 days after initiation & in children with congenital heart disease - increased risk for myocardial infarction within the 1st 2 months of treatment - increased risk of hypertension 4-7 days after initiation [18] 5) other [2,5,10] - dry throat - hallucinations - suicidal ideation - risk of suicide attempts is not due to methylphenidate but precedes it [19] - no increased risk for suicide attempt after 90 days ofbmethylphenidate [19] - psychotic or violent behavior - no risk of psychosis or mania [23] - chest pain - Concerta tablets do NOT dissolve completely; ghost tablets may be seen in feces - Daytrana patch - skin irritation or hypersensitivity - chemical leukoderma [17] - not physically harmful, but is permanent - may affect subsequent tolerance of oral methyphenidate - priapism [15] Drug interactions: 1) methylphenidate decreases antihypertensive effect of guanethidine 2) methylphenidate increases plasma levels of: a) phenytoin b) tricyclic antidepressants (TCA) 3) MAO inhibitors may increase effects of methylphenidate Laboratory: - methylphenidate in specimen - methylphenidate in hair - methylphenidate in gastric fluid - methylphenidate in serum/plasma - methylphenidate in urine Mechanism of action: 1) piperidine derivative, structurally related to amphetamine 2) mild CNS stimulant with actions similar to amphetamine 3) inihibits dopamine reuptake 4) inhibits norepinephrine reuptake Abuse: -> tablets crushed & snorted for intense stimulant effect [7]

Interactions

drug adverse effects (more general classes)

Specific

dextromethylphenidate (Focalin, Focalin-XR DEXmethylphenidate)

General

adrenergic neuron stimulant amine analeptic (CNS stimulant) aromatic compound ester piperidine

Properties

MISC-INFO: elimination route LIVER KIDNEY therapeutic-range 10-40 NG/ML pregnancy-category ? safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Prescriber's Letter 7(8):48 2000
  5. Prescriber's Letter 7(9):51 2000
  6. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  7. Prescriber's Letter 8(2):11 2001
  8. Journal Watch 21(14):117, 2001 Pelham et al, Pediatrics 107:e105, 2001
  9. Prescriber's Letter 9(8):47 2002
  10. Prescriber's Letter 12(8): 2005 Safety Concerns of ADHD Drugs Detail-Document#: 210810 (subscription needed) http://www.prescribersletter.com
  11. Prescriber's Letter 13(2): 2006 Drug Treatment for Attention Deficit Hyperactivity Disorder Detail-Document#: 220214 (subscription needed) http://www.prescribersletter.com
  12. Prescriber's Letter 13(6): 2006 New Drug: Daytrana (Methylphenidate Transdermal System) Detail-Document#: 220606 (subscription needed) http://www.prescribersletter.com
  13. Prescriber's Letter 14(9): 2007 Defective Daytrana Patches Detail-Document#: 230903 (subscription needed) http://www.prescribersletter.com
  14. Deprecated Reference
  15. FDA MedWatch - Dec 17, 2012 Methylphenidate ADHD Medications: Drug Safety Communication - Risk of Long-lasting Erections http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm378876.ht16) - FDA Drug Safety and Availability. Nov 13, 2014 Methylphenidate Hydrochloride Extended Release Tablets (generic Concerta) made by Mallinckrodt and Kudco. [11-13-2014] FDA concerns about therapeutic equivalence with two generic versions of Concerta tablets (methylphenidate hydrochloride extended-release) http://www.fda.gov/Drugs/DrugSafety/ucm422568.htm - Orciari Herman A, Sadoughi S, Saitz R Generic ADHD Drugs Remain on the Market, Despite Lack of Therapeutic Equivalence. Physician's First Watch, June 18, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  16. FDA Safety Alert. 06/24/2015 Daytrana Patch (methylphenidate transdermal system): Drug Safety Communication - Permanent Skin Color Changes. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm452595.htm - FDA Drug Safety Communication: 06/24/2015 FDA reporting permanent skin color changes associated with use of Daytrana patch (methylphenidate transdermal system) for treating ADHD. http://www.fda.gov/Drugs/DrugSafety/ucm452244.htm
  17. Storebo OJ et al Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. BMJ 2015;351:h5203 PMID: 26608309 http://www.bmj.com/content/351/bmj.h5203 - Fazel M Methylphenidate for ADHD. BMJ 2015;351:h5875 PMID: 26608974 http://www.bmj.com/content/351/bmj.h5875
  18. Shin JY et al Cardiovascular safety of methylphenidate among children and young people with attention-deficit/hyperactivity disorder (ADHD): nationwide self controlled case series study. BMJ 2016;353:i2550 PMID: 27245699 Free PMC Article http://www.bmj.com/content/353/bmj.i2550 - Jackson JW The cardiovascular safety of methylphenidate. BMJ 2016;353:i2874 PMID: 27245078 http://www.bmj.com/content/353/bmj.i2874
  19. Man KKC, Coghill D, Chan EW et al Association of Risk of Suicide Attempts With Methylphenidate Treatment. JAMA Psychiatry. Published online July 26, 2017. PMID: 28746699 http://jamanetwork.com/journals/jamapsychiatry/article-abstract/2645499
  20. Padala PR, Padala KP, Lensing SY et al. Methylphenidate for apathy in community-dwelling older veterans with mild Alzheimer's disease: A double-blind, randomized, placebo-controlled trial. Am J Psychiatry 2017 Sep 15 PMID: 28945120
  21. LeBlond E, Smith-Paine J, Riemersma JJ et al. Influence of methylphenidate on long-term neuropsychological and everyday executive functioning after traumatic brain injury in children with secondary attention problems. J Int Neuropsychol Soc 2019 Aug; 25:740-749. PMID: 31178001
  22. Windle ML Rapid Rx Quiz: Stimulants Medscape.Oct 23, 2022 https://reference.medscape.com/viewarticle/981392
  23. Moran LV, Skinner JP, Shinn AK et al Risk of Incident Psychosis and Mania With Prescription Amphetamines. Am J Psychiatry. 2024 Sep 12:appiajp20230329. PMID: 39262211