For a patient aged 6 years or older with ADHD, how do Azstarys (serdexmethylphenidate/dexmethylphenidate) and Vyvanse (lisdexamfetamine) compare in terms of FDA approval, dosing regimens, duration of effect, safety profile, and abuse potential?

Azstarys vs Vyvanse for ADHD Treatment

Both Azstarys (serdexmethylphenidate/dexmethylphenidate) and Vyvanse (lisdexamfetamine) are FDA-approved, first-line stimulant medications for ADHD in patients aged 6 years and older, with the choice between them primarily determined by the need for abuse-deterrent properties and duration of effect preferences. 1

FDA Approval and Age Indications

• Azstarys is FDA-approved for patients aged ≥6 years with ADHD 2, 3
• Vyvanse is FDA-approved for children aged 6-12 years and adults aged 18-55 years with ADHD 4
• Both medications fall under the American Academy of Pediatrics' Grade A recommendation for FDA-approved stimulant medications in elementary and middle school-aged children (6-12 years) 1

Mechanism and Pharmacokinetics

Azstarys (SDX/d-MPH)

• Contains a prodrug (serdexmethylphenidate) combined with immediate-release dexmethylphenidate in a 3:1 ratio 3
• The prodrug component is enzymatically converted to d-methylphenidate, providing extended duration 3
• Demonstrates rapid onset at 0.5 hours post-dose with sustained efficacy extending to 13 hours 3

Vyvanse (Lisdexamfetamine)

• A prodrug of dextroamphetamine covalently bound to l-lysine, activated during first-pass metabolism 4
• Rate-limited enzymatic biotransformation occurs in erythrocyte cells 1
• Provides approximately 12 hours duration of activity with once-daily dosing 4

Dosing Regimens

Azstarys

• Starting dose: 39.2 mg/7.8 mg once daily 3
• Maximum dose: 52.3 mg/10.4 mg once daily 3
• Titration occurs weekly during a 3-week optimization phase 3

Vyvanse

• Starting dose typically 20-30 mg once daily 1
• Maximum dose: 70 mg/day 1
• Dose adjustments made in increments over 2-4 weeks 5

Duration of Effect

• Azstarys demonstrates efficacy from 0.5 to 13 hours post-dose, providing slightly longer coverage than Vyvanse 3
• Vyvanse provides approximately 12 hours of symptom control 4
• Both medications eliminate the need for midday dosing at school 6, 4

Safety Profile

Common Adverse Events (Both Medications)

• Decreased appetite (18.5% for Azstarys) 2
• Insomnia 4, 2
• Headache (>10% incidence) 4
• Weight loss 2, 7
• Upper respiratory tract infections and nasopharyngitis 2

Cardiovascular Considerations

• Neither medication showed clinically meaningful trends in ECG abnormalities, cardiac events, or blood pressure changes leading to discontinuation in clinical trials 2
• Both require monitoring for cardiovascular adverse effects including sudden cardiac death risk, as with all CNS stimulants 4, 7

Growth Effects

• Concerns about growth suppression apply to both medications, as they are CNS stimulants 7
• Regular monitoring of height and weight is necessary 1

Abuse Potential

Vyvanse (Lower Abuse Risk)

• The American Academy of Pediatrics specifically identifies lisdexamfetamine (Vyvanse) as having "less abuse potential" compared to other stimulants 1
• Only activated after ingestion when metabolized by erythrocyte cells to dexamphetamine, making extraction difficult 1
• Particularly recommended for adolescents at risk for medication diversion 1

Azstarys (Moderate Abuse Risk)

• Contains immediate-release dexmethylphenidate component, which theoretically could be extracted 3
• The prodrug component provides some abuse deterrence through rate-limited conversion 3
• Classified as a controlled substance requiring careful monitoring 6

Clinical Decision Algorithm

Choose Vyvanse when:

• Adolescent patient with substance abuse concerns or high diversion risk 1
• Family history of substance use disorder 1
• Patient requires maximum abuse-deterrent properties 1

Choose Azstarys when:

• Patient requires the longest possible duration of effect (up to 13 hours) 3
• Rapid onset of action is critical (0.5 hours vs typical stimulant onset) 3
• Patient has not responded optimally to amphetamine-based stimulants 3
• Methylphenidate formulations are preferred over amphetamines 5

Critical Implementation Points

• Both medications must be combined with behavioral interventions (parent training and classroom interventions) per Grade A recommendations 1, 5
• Screen for personal or family history of bipolar disorder, mania, or hypomania before initiating either medication 5
• Educational supports (IEP or 504 plan) are mandatory components of treatment, not optional 1
• Monitor for signs of medication misuse or diversion, particularly in adolescents 1

Long-Term Safety Data

• Azstarys demonstrated sustained efficacy and safety over 12 months with no unexpected safety findings 2
• The safety profile remained comparable to other methylphenidate products throughout the year-long study 2
• Discontinuation rates and adverse event profiles remained stable during long-term treatment 2