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Methylphenidate Controlled-Delivery Capsules (Equasym™XL, Metadate CD™)

A Review of its Use in the Treatment of Children and Adolescents with Attention-Deficit Hyperactivity Disorder

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Summary

Abstract

Controlled-delivery methylphenidate (methylphenidate CD) [Equasym™XL, Metadate CD™], an oral stimulant, is approved in the US and EU to treat children aged ≥6 years who have been diagnosed with attention-deficit hyperactivity disorder (ADHD).

Once-daily methylphenidate CD is generally well tolerated and effective in the treatment of children and adolescents with ADHD. Methylphenidate CD resulted in superior control of ADHD symptoms compared with osmotic release oral system (OROS®) methylphenidate over a time period corresponding to that of an average school day in a laboratory classroom. In 3-week clinical trials conducted in a community setting, methylphenidate CD was superior to placebo and noninferior to methylphenidate immediate-release (IR) in the treatment of children and adolescents with ADHD. Thus, methylphenidate CD should be considered an important primary treatment on its own or in addition to behavioral and psychosocial interventions, for when a reduction in ADHD symptoms is required during the school day in preference to the evening.

Pharmacologic Properties

Methylphenidate CD is a CNS stimulant that is thought to inhibit the reuptake of dopamine and norepinephrine (noradrenaline) into the presynaptic neuron. The increase in these monoamines in the extraneuronal space may be responsible for the improvement in ADHD symptoms observed with methylphenidate treatment. Improvements in cognitive function, behavior, accuracy, reaction time, short-term memory, vigilance, impulsivity control, and possibly learning have been observed with the use of methylphenidate.

Oral methylphenidate CD has a biphasic, dose-proportional pharmacokinetic profile, with peak plasma concentrations reached at ≈1.5 and ≈4.5 hours. The bioavailability of methylphenidate CD is ≈28% (with breakfast). Although foods such as applesauce do not affect the absorption profile of methylphenidate CD, a high-fat meal can alter the bioavailability of the stimulant. Elimination of methylphenidate CD is mainly though the urinary elimination of ritalinic acid. Methylphenidate CD has an elimination half-life of ≈6 hours.

Clinical Efficacy

The effect of methylphenidate CD on ADHD symptoms in children was compared with that of OROS® methylphenidate and placebo in a well designed trial conducted in a laboratory classroom (the COMACS study). In the COMACS study, significantly lower Swanson, Kotkin, Atkins, M-Flynn, and Pelham Deportment (SKAMP-D) scores were seen with methylphenidate CD than with OROS® methylphenidate from 1.5 through to 4.5 hours after drug administration, and for 7.5 hours versus placebo. A summary score averaging SKAMP-D scores over 1.5–7.5 hours post-dose revealed a significantly lower SKAMP-D score for methylphenidate CD than for OROS® methylphenidate over this time period.

The clinical efficacy of methylphenidate CD in children and/or adolescents with ADHD was also shown in two well designed, 3-week, placebo-controlled trials, one of which was also a noninferiority trial with methylphenidate IR, and a 3-week, noncomparative postmarketing study, all of which were conducted in a community setting. The noninferiority of methylphenidate CD to methylphenidate IR was shown when the lower limit of the confidence interval for the between-group difference in the inattention/overactivity (I/O) component of the Teacher’s Inattention/Overactivity With Aggression (IOWA) Conners’ rating scale was greater than the set limit (−1.5 points) at week 3. Methylphenidate CD was significantly more effective than placebo in reducing the symptoms of ADHD as seen by a significantly lower score (improvement) in the I/O component of the overall ten-item Teacher’s IOWA Conners’ rating scale in one placebo-controlled trial and a significant reduction from baseline in the Conners’ Teacher Global Index in the other placebo-controlled trial. In addition, 65% of methylphenidate CD recipients responded to treatment on the Clinical Global Index improvement subscale in the postmarketing study.

Tolerability

Methylphenidate CD 20–60mg once daily was generally well tolerated in children and adolescents with ADHD; adverse events were usually of mild severity. In four studies, the most commonly reported adverse events in methylphenidate CD recipients were headache, anorexia, abdominal pain, and insomnia. No clinically significant changes in parameters such as hematology, biochemistry, urinalysis, or vital signs were noted in two studies, although one study observed a small decrease in systolic blood pressure and a small increase in heart rate.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. American Academy of Pediatrics. Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics 2000; 105(5): 1158–70

    Article  Google Scholar 

  2. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet 2005 Jul 16; 366(9481): 237–48

    Article  PubMed  Google Scholar 

  3. Faraone SV, Sergeant J, Gillberg C, et al. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2003 Jun; 2(2): 104–13

    PubMed  Google Scholar 

  4. UCB Inc. Once daily Metadate CD™ (methylphenidate HCL, USP) extended-release capsules: prescribing information [online]. Available from URL: http://www.ucb-group.com [Accessed 2006 Jul 21]

  5. 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

    Article  PubMed  CAS  Google Scholar 

  6. Kimko HC, Cross JT, Abernethy DR. Pharmacokinetics and clinical effectiveness of methylphenidate. Clin Pharmacokinet 1999 Dec; 37(6): 457–70

    Article  PubMed  CAS  Google Scholar 

  7. Greenhill LL, Halperin JM, Abikoff H. Stimulant medications. J Am Acad Child Adolesc Psychiatry 1999 May; 38(5): 503–12

    Article  PubMed  CAS  Google Scholar 

  8. Markowitz JS, Patrick KS. Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet 2001; 40(10): 753–72

    Article  PubMed  CAS  Google Scholar 

  9. Lyseng-Williamson KA, Keating GM. Extended-release methylphenidate (Ritalin® LA). Drugs 2002; 62(15): 2251–9

    Article  PubMed  CAS  Google Scholar 

  10. Rapport MD, Moffitt C. Attention deficit/hyperactivity disorder and methylphenidate: a review of height/weight, cardiovascular, and somatic complaint side effects. Clin Psychol Rev 2002 Nov; 22(8): 1107–31

    Article  PubMed  Google Scholar 

  11. Anderson VR, Scott LJ. Methylphenidate transdermal system: in attention-deficit hyperactivity disorder in children. Drugs 2006; 66(8): 1117–26

    Article  PubMed  CAS  Google Scholar 

  12. Wigal SB, Sanchez DY, DeCory HH, et al. Selection of the optimal dose ratio for a controlled-delivery formulation of methylphenidate. J Appl Res 2003; 3(1): 46–63

    CAS  Google Scholar 

  13. Swanson JM, Wigal SB, Wigal T, et al. A comparison of once-daily extended-release methylphenidate formulations in children with attention-deficit/hyper-activity disorder in the laboratory school (the Comacs study). Pediatrics 2004 Mar; 113(3): e206–16

    Article  PubMed  Google Scholar 

  14. Findling RL, Quinn D, Hatch SJ, et al. Comparison of the clinical efficacy of twice-daily Ritalin® and once-daily Equasym™ XL with placebo in children with attention deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry. Epub 2006 Jul 21

    Google Scholar 

  15. Greenhill LL, Findling RL, Swanson JM, et al. A double-blind, placebo-controlled study of modified-release methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics 2002 Mar; 109(3): E39

    Article  PubMed  Google Scholar 

  16. Hirshey Dirksen SJ, D’Imperio JM, Birdsall D, et al. A postmarketing clinical experience study of Metadate® CD. Curr Med Res Opin 2002; 18(7): 371–80

    Article  Google Scholar 

  17. MTA Cooperative Group. National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: changes in effectiveness and growth after the end of treatment. Pediatrics 2004 Apr; 113(4): 762–9

    Article  Google Scholar 

  18. Spencer TJ, Faraone SV, Biederman J, et al. Does prolonged therapy with a long-acting stimulant suppress growth in children with ADHD? J Am Acad Child Adolesc Psychiatry 2006 May; 45(5): 527–37

    Article  PubMed  Google Scholar 

  19. Pliszka SR, Matthews TL, Braslow KJ, et al. Comparative effects of methylphenidate and mixed salts amphetamine on height and weight in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2006 May; 45(5): 520–6

    Article  PubMed  Google Scholar 

  20. Pentikis HS, Simmons RD, Benedict MF, et al. Methylphenidate bioavailability in adults when an extended-release multiparticulate formulation is administered sprinkled on food or as an intact capsule. J Am Acad Child Adolesc Psychiatry 2002 Apr; 41(4): 443–9

    Article  PubMed  Google Scholar 

  21. Rochdi M, Gonzalez MA, Hirshey Dirksen SJ. Dose-proportional pharmacokinetics of a methylphenidate extended-release capsule. Int J Clin Pharmacol Ther 2004 May; 42(5): 285–92

    PubMed  CAS  Google Scholar 

  22. UCB Pharma Limited. Equasym™ XL 10mg, 20mg or 30mg capsules: summary of product characteristics [online]. Available from URL: http://www.ucb-group.com [Accessed 2006 Aug 4]

  23. Markowitz JS, Straughn AB, Patrick KS. Advances in the pharmacotherapy of attention-deficit-hyperactivity disorder: focus on methylphenidate formulations. Pharmacotherapy 2003; 23(10): 1281–99

    Article  PubMed  CAS  Google Scholar 

  24. Chan YP, Swanson JM, Soldin SS, et al. Methylphenidate hydrochloride given with or before breakfast: II. Effects on plasma concentration of methylphenidate and ritalinic acid. Pediatrics 1983 Jul; 72(1): 56–9

    PubMed  CAS  Google Scholar 

  25. Swanson JM, Sandman CA, Deutsch C, et al. Methylphenidate hydrochloride given with or before breakfast: I. Behavioral, cognitive, and electrophysiologic effects. Pediatrics 1983 Jul 1; 72(1): 49–55

    PubMed  CAS  Google Scholar 

  26. Gonzalez MA, Pentikis HS, Anderl N, et al. Methylphenidate bioavailability from two extended-release formulations. Int J Clin Pharmacol Ther 2002 Apr; 40(4): 175–84

    PubMed  CAS  Google Scholar 

  27. Sonuga-Barke EJ, Swanson JM, Coghill D, et al. Efficacy of two once-daily methylphenidate formulations compared across dose levels at different times of the day: preliminary indications from a secondary analysis of the COMACS study data. BMC Psychiatry 2004 Sep 30; 4: 28

    Article  PubMed  Google Scholar 

  28. Kutcher S, Aman M, Brooks SJ, et al. International consensus statement on attention-deficit/hyperactivity disorder (ADHD) and disruptive behaviour disorders (DBDs): clinical implications and treatment practice suggestions. Eur Neuropsychopharmacol 2004 Jan; 14(1): 11–28

    Article  PubMed  CAS  Google Scholar 

  29. Taylor E, Döpfner M, Sergeant J, et al. European clinical guidelines for hyperkinetic disorder: first upgrade. Eur Child Adolesc Psychiatry 2004; 13Suppl. 1: I7–30

    PubMed  Google Scholar 

  30. Reeves G, Schweitzer J. Pharmacological management of attention-deficit hyperactivity disorder. Expert Opin Pharmacother 2004; 5(6): 1313–20

    Article  PubMed  CAS  Google Scholar 

  31. Greydanus DE, Pratt HD, Sloane MA, et al. Attention-deficit/hyperactivity disorder in children and adolescents: interventions for a complex costly clinical conundrum. Pediatr Clin North Am 2003; 50(5): 1049–92

    Article  PubMed  Google Scholar 

  32. American Academy of Pediatrics. Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics 2001 Oct; 108(4): 1033–44

    Article  Google Scholar 

  33. Banaschewski T, Coghill D, Santosh P, et al. Long-acting medications for the hyperkinetic disorders: a systematic review and European treatment guideline. Eur Child Adolesc Psychiatry. Epub 2006 May 5

    Google Scholar 

  34. Methylphenidate hydrochloride. In: McEvoy GK, Snow EK, editors. AHFS drug information 2006. Betheseda (MD): American Society of Health-System Pharmacists, Inc., 2006: 2436–42

  35. Coghill D. Current issues in child and adolescent psychopharmacology: part 1. Attention-deficit hyperactivity and affective disorders. Adv Psychiatr Treat 2003; 9(2): 86–94

    Article  Google Scholar 

  36. Horrigan JP, Kohli RR. The impact of dosing frequency on psychostimulant compliance in ADHD [abstract]. 42nd annual New Clinical Drug Evaluation Unit meeting; 2002 Jun 10–13; Baco Raton (FL)

  37. Connor DF, Steingard RJ. New formulations of stimulants for attention-deficit hyperactivity disorder: therapeutic potential. CNS Drugs 2004; 18(14): 1011–30

    Article  PubMed  CAS  Google Scholar 

  38. Ross RG. Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder. Am J Psychiatry 2006 Jul; 163(7): 1149–52

    Article  PubMed  Google Scholar 

  39. Kratochvil CJ. Newer agents and formulations for the treatment of ADHD. Adv Studies Med 2003; 3(5C): S452–7

    Google Scholar 

  40. McKeage K, Scott LJ. SLI-381 (Adderall XR®). CNS Drugs 2003; 17(9): 669–75

    Article  PubMed  CAS  Google Scholar 

  41. Keating GM, McClellan K, Jarvis B. Methylphenidate (OROS® formulation). CNS Drugs 2001; 15(6): 495–500

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

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Corresponding author

Correspondence to Vanessa R. Anderson.

Additional information

Various sections of the manuscript reviewed by: F.X. Castellanos, Institute for Pediatric Neuroscience, New York University Child Study Center, New York University School of Medicine, New York, New York, USA; D.E. Greydanus, Pediatrics and Human Development, Michigan State University, Kalamazoo, Michigan, USA; M.D. Rappley, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA; V. Roessner, Department of Child and Adolescent Psychiatry, University of Goettingen, Goettingen, Germany; P.J. Santosh, Centre for Interventional Paediatric Psychopharmacology, Department of Child & Adolescent Mental Health, Great Ormond Street Hospital for Children, London, England; C.K. Varley, Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘methylphenidate’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE, and AdisBase search terms were ‘methylphenidate’ and (‘controlled release’ or ‘extended release’ or ‘modified release’). Searches were last updated 2 October 2006.

Selection: Studies in pediatric patients aged 6–17 years with attention-deficit hyperactivity disorder (ADHD) who received controlled-delivery methylphenidate (Metadate CD™ and Equasym™XL). Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Methylphenidate, extended-release, controlled-delivery, ADHD, pharmacodynamics, pharmacokinetics, therapeutic use.

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Anderson, V.R., Keating, G.M. Methylphenidate Controlled-Delivery Capsules (Equasym™XL, Metadate CD™). Pediatr-Drugs 8, 319–333 (2006). https://doi.org/10.2165/00148581-200608050-00005

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