What is the proper usage and dosage of Metadate CD (methylphenidate) for a patient with Attention Deficit Hyperactivity Disorder (ADHD)?

Metadate CD: Proper Usage and Dosage for ADHD

Primary Indication and Patient Selection

Metadate CD (methylphenidate extended-release) is FDA-approved for treating ADHD in patients 6 years and older, delivering once-daily symptom control through a microbead technology that provides 8-hour coverage, with particular strength during the school day. 1, 2

• Metadate CD is indicated for ADHD in adults and pediatric patients 6 years of age and older, as well as for narcolepsy 1
• This formulation utilizes microbead technology to provide extended-release effects lasting approximately 8 hours, making it particularly effective for school-day symptom control 2, 3

Dosing Recommendations

Pediatric Patients (6 Years and Older)

Start with 5 mg twice daily before breakfast and lunch (preferably 30-45 minutes before meals), then increase gradually by 5-10 mg weekly based on response. 1

• The recommended starting dosage is 5 mg orally twice daily 1
• Titrate in increments of 5-10 mg weekly to achieve optimal symptom control 1
• Daily dosage above 60 mg is not recommended 1
• Maximum behavioral effects occur when plasma concentrations are increasing, typically 1-3 hours post-dose 2

Adult Patients

Administer in divided doses 2-3 times daily, preferably 30-45 minutes before meals, with an average dosage of 20-30 mg daily and a maximum of 60 mg daily. 1

• The maximum recommended daily dose is 60 mg for adults 1
• For patients unable to sleep if medication is taken late in the day, administer the last dose before 6 p.m. 1
• Weight-based dosing is not clinically useful due to high variability in individual behavioral responses 2

Special Population Considerations

Preschool-Aged Children (4-5 Years)

Behavioral therapy should be initiated first for preschool-aged children, with methylphenidate reserved only for those with moderate-to-severe dysfunction who have not responded adequately to behavioral interventions. 4, 5

• Only preschool-aged children with moderate-to-severe dysfunction should be considered for medication, defined as symptoms persisting for at least 9 months with dysfunction in both home and other settings 4
• Methylphenidate metabolism is slower in children 4-5 years of age, requiring lower starting doses and smaller incremental increases 4, 5
• Concerns about effects on growth during this rapid growth period support prioritizing behavioral therapy first 4

Adolescents (12-18 Years)

Before initiating treatment in adolescents, assess for substance use symptoms and monitor for medication diversion, considering longer-acting formulations to provide coverage during driving hours. 4

• Screen adolescents for active substance use before beginning medication; if identified, refer to a subspecialist 4
• Monitor prescription refill requests for signs of misuse or diversion by the patient, parents, classmates, or acquaintances 4
• Provide medication coverage for symptom control while driving, as adolescents with ADHD face increased risks of crashes and motor vehicle violations 4

Clinical Efficacy and Comparative Effectiveness

Metadate CD provides superior symptom control during the morning and school day (1.5-6 hours post-dose) compared to OROS methylphenidate (Concerta), making it particularly advantageous when daytime symptom control is the priority. 3, 6, 7

• In laboratory classroom studies, Metadate CD resulted in superior control of ADHD symptoms compared to OROS methylphenidate during the average school day 3, 6
• Lower daily doses of Metadate CD (20-40 mg) provided equivalent morning symptom control to higher doses of Concerta (36-54 mg), allowing for reduced total daily MPH exposure 7
• In clinical trials, 65% of patients demonstrated a positive response (CGI Global Improvement rating of very much or much improved) 8
• Among previously treated patients, 71% rated Metadate CD as much better or better than their previous methylphenidate treatment 8

Pretreatment Screening Requirements

Before prescribing Metadate CD, assess for cardiac disease through careful history, family history of sudden death or ventricular arrhythmia, and physical examination, and evaluate family history for motor/verbal tics or Tourette's syndrome. 1

• Perform cardiac assessment including history of structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease 1
• Clinically evaluate patients for tics or Tourette's syndrome before initiating treatment 1
• Screen patients for risk factors for developing manic episodes prior to initiation 1

Critical Safety Considerations and Monitoring

Abuse Potential and Controlled Substance Status

Metadate CD is a Schedule II controlled substance with high potential for abuse and misuse; assess each patient's risk before prescribing and monitor throughout treatment for signs of diversion or substance use disorder. 1

• Misuse and abuse can result in overdose and death, with increased risk at higher doses or unapproved methods of administration (snorting, injection) 1
• Educate patients and families about proper storage (preferably locked) and disposal of unused medication 1
• Throughout treatment, reassess each patient's risk and frequently monitor for signs of abuse, misuse, and addiction 1

Cardiovascular Monitoring

Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease; monitor blood pressure and pulse regularly during treatment. 1

• Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious cardiac problems 1
• Monitor blood pressure and heart rate throughout treatment 1

Growth Suppression

Closely monitor height and weight in pediatric patients, as long-term stimulant use may suppress growth by 1-2 cm, with effects diminishing by the third year of treatment. 4, 1

• The MTA study revealed more persistent effects of stimulants on decreasing growth velocity than previous studies, particularly with higher and more consistently administered doses 4
• Pediatric patients not growing or gaining height or weight as expected may need treatment interruption 1

Psychiatric Adverse Reactions

Screen for risk factors for manic episodes before initiating treatment; if new psychotic or manic symptoms occur, consider discontinuing Metadate CD. 1

• An uncommon but significant adverse effect is the occurrence of hallucinations and other psychotic symptoms 4
• Prior to initiating treatment, screen patients for risk factors for developing a manic episode 1

Ophthalmologic Monitoring

Patients at risk for acute angle closure glaucoma (e.g., significant hyperopia) should be evaluated by an ophthalmologist before treatment; prescribe cautiously to patients with open-angle glaucoma or increased intraocular pressure. 1

• Closely monitor patients with a history of increased IOP or open-angle glaucoma 1
• Only prescribe if the benefit of treatment outweighs the risk in these populations 1

Common Adverse Effects

The most common adverse reactions include tachycardia, palpitations, headache, insomnia, anxiety, hyperhidrosis, weight loss, decreased appetite, dry mouth, nausea, and abdominal pain. 1

• Appetite suppression and insomnia are the most commonly reported adverse effects 2
• Preschool-aged children may experience increased mood lability and dysphoria 4
• Methylphenidate has a wide margin of safety with relatively mild adverse effects 2

Dosage Adjustment and Discontinuation

If paradoxical aggravation of symptoms or adverse reactions occur, reduce dosage or discontinue; if no improvement after one month of appropriate dosage adjustment, discontinue treatment. 1

• Reduce dosage if paradoxical aggravation of symptoms or other adverse reactions occur 1
• If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue Metadate CD 1

Contraindications

Do not prescribe Metadate CD to patients with known hypersensitivity to methylphenidate or those receiving MAOIs or within 14 days of MAOI discontinuation. 1

• Contraindicated in patients with known hypersensitivity to methylphenidate or other components; hypersensitivity reactions including angioedema and anaphylactic reactions have been reported 1
• Contraindicated during treatment with MAOIs or within 14 days following MAOI discontinuation due to risk of hypertensive crises 1

Combination and Multimodal Treatment

Behavioral therapy combined with stimulant medication offers superior outcomes for functional performance beyond medication alone, particularly when ADHD coexists with other conditions. 4

• Studies indicate that behavioral therapy has positive effects when combined with medication for preadolescent children 4
• Only extended-release guanfacine and extended-release clonidine have FDA approval as adjunctive therapy with stimulant medications 4
• Other medications used in combination off-label lack sufficient evidence for safety or efficacy and cannot be recommended 4

Clinical Pearls and Common Pitfalls

Individual behavioral responses to methylphenidate are highly variable; start at low doses and titrate to maximally effective dosage regardless of weight, as plasma concentration monitoring is not clinically useful. 2

• Because of variability in behavioral responses, assessment of plasma concentrations is not clinically useful, nor does weight help in deciding appropriate dosage 2
• Maximum behavioral effects occur when plasma concentrations are increasing, not at peak levels 2
• Patients previously treated with immediate-release or extended-release tablet formulations can be successfully converted to Metadate CD at a comparable dose 8
• The 8-hour duration of Metadate CD makes it particularly suitable when reduction in ADHD symptoms is required during the school day rather than into the evening 3, 6