What is the appropriate method to switch a patient from Azstarys 26 mg (serdexmethylphenidate/dexmethylphenidate) to Focalin (dexmethylphenidate)?

Switching from Azstarys 26 mg to Focalin: Direct Conversion Protocol

Convert Azstarys 26 mg to Focalin 10 mg twice daily (or Focalin XR 20 mg once daily), as Azstarys 26 mg contains 13 mg of dexmethylphenidate equivalent, and a 1:1.5 to 1:2 ratio accounts for the prodrug conversion and provides comparable therapeutic coverage. 1

Understanding the Azstarys Formulation

Azstarys combines serdexmethylphenidate (a prodrug) with immediate-release dexmethylphenidate in a single capsule. The 26 mg dose contains approximately 13 mg of dexmethylphenidate equivalent after accounting for the prodrug conversion. 2 The prodrug component is designed to avoid rapid plasma spikes and provide extended duration while the immediate-release portion delivers early onset. 3

Direct Conversion Strategy

Start Focalin immediate-release at 10 mg twice daily (morning and early afternoon) or Focalin XR 20 mg once daily in the morning. 4, 5 This provides equivalent total daily dexmethylphenidate exposure while maintaining symptom coverage throughout the day.

Rationale for the 1:1.5–2 Conversion

• Azstarys 26 mg delivers approximately 13 mg of active dexmethylphenidate through its dual-component system 2
• Focalin immediate-release at 10 mg twice daily (20 mg total) or Focalin XR 20 mg provides comparable therapeutic effect 4, 5
• The slightly higher Focalin dose compensates for differences in delivery kinetics between the prodrug formulation and standard dexmethylphenidate 3

Formulation Selection

Focalin XR (Extended-Release) – Preferred Option

Focalin XR 20 mg once daily provides bimodal release mimicking two doses of immediate-release dexmethylphenidate given 4 hours apart, with symptom control lasting 11–12 hours. 5, 6 This formulation:

• Eliminates the need for midday dosing at school or work 5
• Can be opened and sprinkled on applesauce for patients unable to swallow capsules 5
• Demonstrates efficacy from 0.5 hours post-dose through 12 hours 5, 6
• Provides more stable plasma concentrations than immediate-release formulations 6

Focalin Immediate-Release – Alternative Option

Focalin IR 10 mg twice daily (morning and 4 hours later) offers flexibility for patients requiring dose adjustments or those who prefer shorter-acting coverage. 4, 7 This approach allows:

• Fine-tuning of individual doses based on symptom patterns 1
• Avoidance of late-day coverage if evening symptoms are not problematic 1
• Lower cost compared to extended-release formulations 4

Implementation Protocol

Day 1 of Switch

• Discontinue Azstarys immediately – no washout period is required as both medications are methylphenidate-class stimulants 1
• Initiate Focalin XR 20 mg in the morning (or Focalin IR 10 mg morning and early afternoon) 4, 5
• Monitor for adequate symptom control throughout the first day, particularly during the 1–4 hour and 8–12 hour windows 5

Week 1–2 Monitoring

• Assess ADHD symptom control using standardized rating scales 1
• Monitor blood pressure and pulse at baseline and during the first two weeks 1, 3
• Track appetite, sleep quality, and any emergence of headache or irritability 4, 7
• Document timing of symptom breakthrough to guide potential dose adjustments 5

Dose Titration if Needed

If symptom control is inadequate after 1 week at Focalin XR 20 mg, increase to 25–30 mg once daily; for Focalin IR, increase to 12.5–15 mg twice daily. 1, 6 Maximum recommended doses are:

• Focalin XR: 40 mg daily in adults, 30 mg daily in children 6
• Focalin IR: 20 mg twice daily (40 mg total) in adults 1, 4

If symptoms are over-controlled or side effects emerge, reduce to Focalin XR 15 mg or Focalin IR 7.5 mg twice daily. 4, 7

Critical Safety Considerations

Cardiovascular Monitoring

• Measure blood pressure and pulse before switching and at each follow-up visit during titration 1, 3
• Dexmethylphenidate has a cardiovascular safety profile similar to other methylphenidate formulations 7, 6
• Avoid use in patients with symptomatic cardiovascular disease or uncontrolled hypertension 1

Common Side Effects

The most frequent adverse effects with Focalin are diminished appetite and insomnia, occurring at rates similar to other stimulants. 4, 7 These can be managed by:

• Administering the medication after meals to minimize appetite suppression 1
• Ensuring the last dose is given no later than early afternoon (for IR formulations) 1
• Considering a dose reduction if side effects are prohibitive 4

Abuse Potential Considerations

Focalin is a Schedule II controlled substance with abuse potential comparable to other methylphenidate products. 8 However, Focalin XR's extended-release mechanism provides lower abuse risk than immediate-release formulations due to more gradual onset and sustained plasma levels. 5, 6

Monitoring Timeline

First Week

• Daily patient/caregiver report of symptom control and side effects 1
• Formal assessment at day 3–5 to confirm adequate conversion 5

Weeks 2–4

• Weekly rating scales to document ADHD symptom response 1
• Cardiovascular parameters at week 2 and week 4 3
• Height and weight measurement (particularly in pediatric patients) 1

Maintenance Phase

• Monthly follow-up until stable, then quarterly visits 1
• Ongoing monitoring for tolerance development, though this is rare with proper dosing 1

Common Pitfalls to Avoid

Do not assume a 1:1 mg-for-mg conversion between Azstarys and Focalin – the prodrug component in Azstarys requires accounting for molecular weight differences and delivery kinetics. 2, 3

Do not initiate Focalin at doses lower than 15–20 mg total daily in patients previously stable on Azstarys 26 mg, as this will likely result in inadequate symptom control. 4, 5

Do not combine Focalin with MAO inhibitors or initiate within 14 days of MAOI discontinuation due to risk of hypertensive crisis. 1

Do not exceed maximum recommended doses (Focalin XR 40 mg daily or Focalin IR 20 mg twice daily) without clear documentation that lower doses were insufficient and higher doses produce no prohibitive side effects. 1, 6

Expected Outcomes

Approximately 70–80% of patients achieve good symptom control when methylphenidate-class stimulants are properly titrated. 1, 3 The switch from Azstarys to Focalin should maintain therapeutic benefit while potentially offering advantages in:

• Cost (if insurance coverage favors Focalin) 4
• Dosing flexibility (with immediate-release formulations) 4
• Duration of action (Focalin XR provides 11–12 hours of coverage) 5, 6

If adequate response is not achieved after 2–4 weeks of optimized Focalin dosing, consider switching to an amphetamine-based stimulant rather than further dose escalation, as approximately 40% of patients respond preferentially to one stimulant class over the other. 1, 3