Introduction
Concerta (methylphenidate HCl extended-release) is a central nervous system stimulant prescription medication approved for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). It belongs to the methylphenidate class of medications and utilizes a unique osmotic controlled-release delivery system (OROS) that provides extended duration of effect with once-daily dosing.
Mechanism of Action
Methylphenidate, the active ingredient in Concerta, is a central nervous system stimulant that blocks the reuptake of norepinephrine and dopamine into presynaptic neurons by binding to and blocking the dopamine transporter (DAT) and norepinephrine transporter (NET). This action increases the extracellular concentrations of these neurotransmitters in specific brain regions, particularly the prefrontal cortex, which is involved in attention, executive function, and impulse control. The exact mechanism by which methylphenidate produces its therapeutic effects in ADHD is not fully understood but is believed to involve enhancement of dopaminergic and noradrenergic neurotransmission.
Indications
- Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children 6 years and older, adolescents, and adults
- As part of a comprehensive treatment program that may include psychological, educational, and social interventions
Dosage and Administration
Initial Dose:- Children and adolescents (6-17 years): 18 mg once daily in the morning
- Adults: 18 or 36 mg once daily in the morning
- May increase weekly in increments of 18 mg
- Maximum recommended dose: 54 mg daily for children 6-12 years; 72 mg daily for adolescents 13-17 years and adults
- Renal impairment: Use with caution
- Hepatic impairment: Use with caution
- Geriatric patients: Not studied; use with caution
- Tablets must be swallowed whole with water; do not crush, chew, or divide
Pharmacokinetics
Absorption: Rapidly absorbed with biphasic characteristics; initial peak concentrations at 1-2 hours, followed by gradual ascending concentrations Distribution: Apparent volume of distribution: 2.6±1.0 L/kg; plasma protein binding: 10-33% Metabolism: Primarily metabolized by de-esterification to alpha-phenyl-piperidine acetic acid (ritalinic acid) via carboxylesterase CES1A1 Elimination: Terminal half-life: approximately 3.5 hours; primarily excreted renally (78-97% of dose in urine as ritalinic acid within 48-96 hours)Contraindications
- Known hypersensitivity to methylphenidate or other product components
- Patients with glaucoma
- Patients with motor tics or Tourette's syndrome, or family history of Tourette's syndrome
- During or within 14 days following MAO inhibitor therapy
- Patients with marked anxiety, tension, or agitation
Warnings and Precautions
Boxed Warning:- High potential for abuse and dependence (CII controlled substance)
- Serious cardiovascular events including sudden death in patients with structural cardiac abnormalities
- exacerbation of pre-existing psychiatric disorders
- Growth suppression in pediatric patients (monitor height and weight)
- Priapism (prolonged and painful erections)
- Peripheral vasculopathy including Raynaud's phenomenon
- Visual disturbances
Drug Interactions
Significant Interactions:- MAO inhibitors: Risk of hypertensive crisis (contraindicated)
- Antihypertensive drugs: May decrease efficacy
- Warfarin: Altered anticoagulant response
- Anticonvulsants (phenobarbital, phenytoin, primidone): Altered concentrations
- Tricyclic antidepressants: Increased concentrations
- Clonidine: Serious adverse events reported
Adverse Effects
Common (≥5%):- Headache (22%)
- Upper abdominal pain (12%)
- Insomnia (12%)
- Decreased appetite (10%)
- Xerostomia (7%)
- Nausea (7%)
- Anxiety (6%)
- Dizziness (6%)
- Irritability (5%)
- Cardiovascular events (sudden death, stroke, MI)
- Psychiatric adverse reactions (psychosis, mania)
- Priapism
- Peripheral vasculopathy
- Growth suppression
Monitoring Parameters
Baseline:- Comprehensive medical history (cardiovascular, psychiatric)
- Physical examination including height, weight, and blood pressure
- Assessment for personal or family history of substance abuse
- Blood pressure and heart rate at each dose adjustment and periodically during treatment
- Height and weight in pediatric patients (plot on growth chart)
- Monitoring for emergence or worsening of aggressive behavior or hostility
- Assessment for signs of drug dependence and abuse
- Evaluation for psychiatric symptoms including psychotic or manic symptoms
Patient Education
- Take medication once daily in the morning with or without food
- Swallow tablets whole with water; do not crush, chew, or divide
- Medication may decrease appetite; maintain proper nutrition
- Report any chest pain, shortness of breath, or fainting
- Immediately report any prolonged or painful erections
- Monitor for emotional lability, aggression, or unusual thoughts
- Keep medication securely stored due to abuse potential
- Do not abruptly discontinue without medical supervision
- Inform all healthcare providers about Concerta use before procedures
References
1. Concerta® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021. 2. Wolraich ML, Hagan JF Jr, Allan C, et al. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2019;144(4):e20192528. 3. Stiefel G, Besag FM. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder. Drug Saf. 2010;33(10):821-842. 4. Kimko HC, Cross JT, Abernethy DR. Pharmacokinetics and clinical effectiveness of methylphenidate. Clin Pharmacokinet. 1999;37(6):457-470. 5. Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018;5(9):727-738.