Azstarys

(serdexmethylphenidate and dexmethylphenidate)

Forms/Strengths

• Capsules: 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, 52.3 mg/10.4 mg 

Dosing

• Age: ≥ 6 y/o
• Onset: ~ 30 min
• Duration: 12-14 hours
• Release Profile: 30% IR, 70% ER
• Considerations: Administer once daily in the morning, with or without food; capsules can be taken whole or opened and sprinkled onto applesauce or mixed with water.
• Initial Dose: 39.2/7.8 mg
• Titration: Increase to 52.3/10.4 mg or decrease to 26.1/5.2 mg after one week
• Max Dose: 52.3/10.4 mg daily

Quick Facts

• Prodrug formulation: 30% immediate-release dexmethylphenidate + 70% delayed-release serdexmethylphenidate (converted to dexmethylphenidate in lower GI tract) for rapid onset and sustained 13-hour effect
• Blocks reuptake of dopamine and norepinephrine into presynaptic neurons, increasing synaptic concentrations
• FDA-approved for ADHD in patients ≥6 years; no generic available
• CII controlled substance with high abuse potential; monitor for misuse
• Common side effects include appetite suppression, insomnia, and increased BP/HR
• Low incidence of next-day rebound vs. other stimulants due to extended PK profile
  

Indications

•  ADHD (ICD-10: F90.0)

Off-Label Uses

•  N/A

How to Take

• Take once daily in the morning to reduce the risk of insomnia.
• Can be taken with or without food.
• Swallow the capsule whole; do not crush or chew.
• If needed, the capsule can be opened, and contents sprinkled on applesauce or water—consume immediately without chewing.

Side Effects

• Common:

  • Decreased appetite, weight loss
  • Insomnia
  • Headache
  • Nausea, stomach pain
  • Increased heart rate or blood pressure

• Serious:

  • Cardiovascular events: Sudden death in patients with pre-existing structural cardiac abnormalities or arrhythmias.
  • Psychiatric symptoms: New or worsening anxiety, psychosis, or manic symptoms.
  • Peripheral vasculopathy, including Raynaud’s phenomenon.

Monitoring / Labs

• Cardiovascular: Baseline and routine monitoring of heart rate and blood pressure.
• Growth in Pediatrics: Regular monitoring of height and weight to detect growth suppression.
• Psychiatric Symptoms: Observe for mood changes, anxiety, or psychosis.
• Abuse Potential: Monitor for misuse or diversion.

Education

• When to Call the Doctor:

  • Severe mood changes, aggression, or suicidal thoughts.
  • Chest pain, rapid heartbeat, shortness of breath (cardiovascular concerns).
  • Uncontrolled movements, tics, or worsening anxiety.
  • Numbness, coldness, or color changes in fingers or toes (circulatory issues).
  • Unexplained weight loss or delayed growth in pediatric patients.

• Safety Tips:

  • Monitor blood pressure and heart rate, especially in patients with cardiovascular risk.
  • Use caution in patients with anxiety, bipolar disorder, or psychosis, as symptoms may worsen.
  • Avoid caffeine and other stimulants, which may amplify side effects.
  • Ensure adequate hydration and nutrition, as appetite suppression is common.
  • Tapering may be required if discontinuing after long-term use.

• Parent Tips for Pediatric Patients:

  • Encourage a nutrient-dense diet to counteract appetite suppression.
  • Administer in the morning before school for optimal effect.
  • Monitor school performance and behavioral changes.
  • Observe for sleep disturbances; adjust timing if necessary.
  • Communicate regularly with teachers and caregivers about medication effects.

Additional Information

• Contraindications:

  • Hypersensitivity to serdexmethylphenidate, dexmethylphenidate, or formulation components.
  • Use within 14 days of MAOI therapy (risk of hypertensive crisis).
  • Symptomatic cardiovascular disease, moderate-to-severe hypertension, hyperthyroidism, glaucoma.
  • History of substance use disorder, unless benefits outweigh risks.

• Pregnancy:

  • Category C; use only if benefits outweigh risks.
  • May cause neonatal withdrawal symptoms or low birth weight.

• Lactation:

  • Excreted in breast milk; not recommended due to potential infant exposure.

• Drug Interactions:

  • Serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs) increase serotonin syndrome risk.
  • Acidifying agents (e.g., ascorbic acid) may reduce drug absorption.
  • Alkalinizing agents (e.g., sodium bicarbonate) may increase dexmethylphenidate levels.
  • May potentiate hypertensive effects of certain medications (e.g., decongestants, beta-agonists).

References

1. AZSTARYS (serdexmethylphenidate and dexmethylphenidate) Prescribing Information, FDA, 2023, https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211555s004lbl.pdf
2. DailyMed: AZSTARYS, NIH, 2024, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f11dd712-5c66-4c3e-9b2b-14d6e9b2b14d
3. UpToDate: Methylphenidate (dexmethylphenidate), 2025, https://www.uptodate.com/contents/methylphenidate-including-dexmethylphenidate-drug-information
4. Clinical Pharmacology Review: AZSTARYS NDA 211555, FDA, 2021, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/211555Orig1s000ClinPharmR.pdf