Introduction
Quillivant XR (methylphenidate hydrochloride) is an extended-release oral suspension formulation of a central nervous system stimulant approved for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). It represents a significant advancement in methylphenidate delivery systems by providing extended duration of effect with the convenience of a liquid formulation, particularly beneficial for patients who have difficulty swallowing tablets or capsules.
Mechanism of Action
Methylphenidate, the active component of Quillivant XR, is believed to block 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 availability of these neurotransmitters in the extraneuronal space, particularly in the prefrontal cortex. The exact mechanism by which methylphenidate exerts its mental and behavioral effects in ADHD patients remains incompletely understood but is thought to involve cortical stimulation and possible activation of the reticular activating system.
Indications
Quillivant XR is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients 6 years and older. The effectiveness of Quillivant XR for this indication has been established in controlled clinical trials in children with ADHD.
Dosage and Administration
Initial Dose: 20 mg once daily in the morning Titration: May increase weekly in increments of 10 mg to 20 mg daily Maximum Dose: 60 mg daily (not to exceed 2 mg/kg for patients <50 kg) Administration: Shake bottle for at least 10 seconds before use. Administer orally using the provided dosing syringe. May be taken with or without food. Special Populations:- Renal Impairment: Use with caution; no specific dosage recommendations
- Hepatic Impairment: Use with caution; no specific dosage recommendations
- Geriatric Patients: Safety and effectiveness not established
- Pediatric Patients: Approved for ages 6 years and older
Pharmacokinetics
Absorption: Peak plasma concentrations achieved approximately 5 hours after administration. The extended-release profile provides therapeutic effects throughout the day with once-daily dosing. Distribution: Apparent volume of distribution is 2.65 L/kg. Plasma protein binding is 10-33%. Metabolism: Primarily metabolized by de-esterification to alpha-phenyl-piperidine acetic acid (ritalinic acid). The metabolic pathway involves carboxylesterase CES1A1. Elimination: Terminal half-life is approximately 3.5 hours. Approximately 78-97% of the dose is excreted in urine and 1-3% in feces as metabolites.Contraindications
- Known hypersensitivity to methylphenidate or other components of Quillivant XR
- Patients with glaucoma
- Patients with pheochromocytoma
- Patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation
- Patients with motor tics or Tourette's syndrome or family history of Tourette's syndrome
Warnings and Precautions
Serious Cardiovascular Events: Sudden death, stroke, and myocardial infarction have been reported in adults with stimulant drugs at usual doses. Use with caution in patients with structural cardiac abnormalities or other serious heart problems. Blood Pressure and Heart Rate Increases: Monitor blood pressure and heart rate at appropriate intervals. Psychiatric Adverse Reactions: May exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychotic disorders. May precipitate mixed/manic episodes in patients with bipolar disorder. Suppression of Growth: Monitor growth during treatment; may need to interrupt therapy if growth is not as expected. Seizures: May lower seizure threshold; use with caution in patients with epilepsy. Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported.Drug Interactions
MAO Inhibitors: Contraindicated due to risk of hypertensive crisis Antihypertensive Drugs: Methylphenidate may decrease the effectiveness of drugs used to treat hypertension Warfarin: Methylphenidate may inhibit warfarin metabolism Anticonvulsants: Methylphenidate may inhibit metabolism of phenobarbital, phenytoin, and primidone Tricyclic Antidepressants: May increase plasma concentrations of tricyclic antidepressants Clonidine: Serious adverse events reported with concomitant use (limited evidence)Adverse Effects
Most Common Adverse Reactions (≥5% and twice the rate of placebo):- Decreased appetite (25%)
- Anxiety (8%)
- Vomiting (7%)
- Decreased weight (7%)
- Nausea (6%)
- Insomnia (6%)
- Abdominal pain (5%)
- Irritability (5%)
- Sudden death in patients with structural cardiac abnormalities
- Stroke and myocardial infarction in adults
- Increased blood pressure and heart rate
- Psychiatric adverse events
- Priapism
- Peripheral vasculopathy including Raynaud's phenomenon
Monitoring Parameters
- Height and weight in pediatric patients (at least every 6 months)
- Blood pressure and heart rate at initiation, following dose changes, and periodically during therapy
- Complete blood count with differential
- Psychiatric symptoms including emergence of new psychotic or manic symptoms
- Signs of drug dependence or abuse
- Visual function if visual disturbances occur
Patient Education
- Take Quillivant XR exactly as prescribed; do not adjust dose without medical supervision
- Shake bottle well for at least 10 seconds before each use
- Use the provided dosing syringe for accurate measurement
- May be taken with or without food
- Report any chest pain, shortness of breath, or fainting to healthcare provider immediately
- Report any new or worsening behavioral problems, aggression, or mood changes
- Inform healthcare provider of all medications being taken, including over-the-counter products
- Store at room temperature; discard any unused portion after 4 months
- Keep out of reach of children due to potential for abuse and dependence
References
1. Quillivant XR [package insert]. New York, NY: Pfizer Inc.; 2022. 2. Childress AC, Wigal SB, Brams MN, et al. Efficacy and safety of extended-release methylphenidate in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2013;23(4):216-225. 3. Faraone SV. The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018;87:255-270. 4. 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. 5. 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.