Azstarys

(serdexmethylphenidate and dexmethylphenidate)
Azstarys (serdexmethylphenidate and dexmethylphenidate); CII
Full Prescribing Information
DailyMed Drug Information
Summary
Azstarys is a once-daily, long-acting capsule containing dexmethylphenidate together with serdexmethylphenidate, a prodrug converted to dexmethylphenidate mainly in the lower gastrointestinal tract, approved for ADHD from age 6. The duration comes from delayed prodrug conversion rather than from a bead or osmotic delivery system, so nothing in the capsule can be damaged by chewing or sprinkling. Its milligram numbers do not compare with any other methylphenidate product. Schedule II; brand only.
Forms & Strengths
Capsules (serdexmethylphenidate / dexmethylphenidate): 26.1 mg / 5.2 mg, 39.2 mg / 7.8 mg, 52.3 mg / 10.4 mg
Dosing
Age:
6-12 y/o: established by a controlled trial and a 12-month open-label safety study
13-17 y/o and adults: established by pharmacokinetic bridging
Under 6 y/o: not recommended; higher plasma exposure and more adverse reactions, including weight loss
Onset: ~ 2 hours fasted, later with food
Duration: up to 13 hours
Release Profile: fixed molar ratio, 30% dexmethylphenidate to 70% serdexmethylphenidate. This is capsule composition, not a bead-release split: the long tail comes from prodrug conversion in the lower gut
Initial Dose: 39.2 mg / 7.8 mg once daily in the morning, in every age band
Titration:
6-12 y/o: after 7 days, increase to 52.3 mg / 10.4 mg or decrease to 26.1 mg / 5.2 mg
13-17 y/o and adults: after 7 days, increase to 52.3 mg / 10.4 mg; no labelled down-titration step
Max Dose: 52.3 mg / 10.4 mg once daily, in every age band
Considerations: Once daily in the morning; food delays the peak about 2 hours without changing exposure. Never substitute for another methylphenidate milligram for milligram; stop it and titrate from the standard start.
Pharmacology
Mechanism: Blocks presynaptic dopamine and norepinephrine reuptake at DAT and NET; does not meaningfully promote catecholamine release at therapeutic doses. Serdexmethylphenidate is inactive until converted.
Delivery / Release: Fixed molar ratio, 30% dexmethylphenidate to 70% serdexmethylphenidate. The free drug peaks at ~2 hours fasted; the prodrug converts in the lower gut and alone peaks at about 8 hours.
Metabolism: The converting enzymes are unidentified; prodrug bioavailability is under 3%, and neither component is a CYP or transporter substrate. Half-life ~5.7 h (prodrug) and ~11.7 h (dexmethylphenidate, absorption-limited). Steady state by the third dose.
Class Positioning: Duration comes from a prodrug rather than beads (Focalin XR) or an osmotic pump (Concerta), so there is no release mechanism to destroy by opening or chewing.
Indications
ADHD (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 6 y/o and older, including adults
Off-Label Uses
Narcolepsy (ICD-10: G47.419): racemic methylphenidate carries the indication; this product does not. Insufficient.
ADHD in a child aged 4 to 5 (ICD-10: F90.x): behavioral parent training first (AAP 2019). Use below 6 is not recommended, and the lowest strength already equals 20 mg. Not the preschool option.
Where the evidence does not support use. AHRQ 2024 grades stimulant head-to-head comparisons as low strength of evidence, so nothing supports the prodrug design outperforming a conventional long-acting methylphenidate, or any use outside ADHD in youth.
Contraindications & Warnings
Boxed Warning: Abuse, misuse, and addiction, which can lead to substance use disorder, overdose and death. Assess risk before prescribing and monitor throughout.
Contraindicated:
Hypersensitivity to serdexmethylphenidate, methylphenidate or any component; bronchospasm, rash and pruritus reported.
Concomitant MAOI, or within 14 days of stopping one; hypertensive crisis.
Use with caution:
Structural cardiac abnormality, cardiomyopathy, serious arrhythmia or coronary disease; the label says avoid.
Pre-existing hypertension, because blood pressure and heart rate rise on stimulants.
Pre-existing psychosis or bipolar disorder; motor or verbal tics and Tourette's syndrome.
Open-angle glaucoma, raised intraocular pressure, or significant hyperopia.
Peripheral vasculopathy including Raynaud's; substance use disorder in patient or household.
Screen before starting:
Cardiac disease by history, family history of sudden death, and exam. No routine ECG.
Personal and family history of tics or Tourette's syndrome.
Risk factors for mania; abuse and diversion risk; baseline height, weight, blood pressure and heart rate.
Drug Interactions
Other methylphenidate products: not an interaction but a substitution hazard the label calls out. Never switch milligram for milligram in either direction; discontinue the other product and titrate from the standard starting dose.
MAOIs (phenelzine, tranylcypromine, selegiline, linezolid, methylene blue): hypertensive crisis. Do not co-prescribe; allow 14 days after stopping.
Antihypertensives (any class): effectiveness may fall. Monitor blood pressure and adjust their dose.
Halogenated anesthetics (sevoflurane, isoflurane, desflurane): sudden intraoperative pressure and rate rise. Avoid on the day of surgery.
Risperidone: a dose change either way may raise EPS risk. Monitor for EPS across any change.
Administration
Once daily in the morning, with or without food. A meal does not change exposure but pushes the peak to 4 or 4.5 hours.
Swallow whole, or empty the contents into 50 mL of water or 2 tablespoons of applesauce and consume it all within 10 minutes of mixing.
There is no release mechanism to destroy; the delay is in the prodrug chemistry.
Switching from another methylphenidate: stop that product and start at 39.2 mg / 7.8 mg. Never convert by milligrams.
Stop the drug if a month of dose adjustment brings no improvement. Store securely, preferably locked.
Side Effects
Common (pooled methylphenidate class rates; no product-specific table exists): decreased appetite, decreased weight, nausea, abdominal pain, vomiting, insomnia, anxiety, affect lability, irritability, increased blood pressure, tachycardia.
Serious:
Sudden death with structural cardiac disease; avoid use, and evaluate exertional syncope promptly.
New psychosis or mania, including with no psychiatric history; consider discontinuing.
Priapism, sometimes requiring surgery, including during drug holidays. Immediate care.
Peripheral vasculopathy including Raynaud's; reduce dose or stop.
Growth suppression: over 12 months in children 6-12, mean z-score change was minus 0.20 for weight and minus 0.21 for height, most in the first 4 months.
Acute angle closure glaucoma and raised intraocular pressure.
Hypersensitivity: bronchospasm, rash and pruritus reported with this product.
Monitoring & Labs
Substitution errors: at every refill and transition of care, confirm no milligram conversion to or from another methylphenidate. The label warns this risks overdose.
Growth: height, weight and BMI at baseline, monthly for the first 4 months, then every 6 months. Most weight z-score loss occurs in those 4 months.
Cardiovascular: blood pressure and heart rate at baseline, at every dose change, and at least every 6 months; a sustained or symptomatic rise triggers dose reduction.
Appetite and sleep: at every visit and dose change. Coverage runs to about 13 hours, so confirm the dosing time before treating insomnia as a dose problem.
Psychiatric, tics and digits: screen for new psychosis, mania, aggression and emergent tics at every visit; inspect fingers and toes.
Abuse and diversion: at every refill reassess risk, reconcile the pill count, and check the state PDMP per state requirement.
Discontinuation & Taper
May be stopped abruptly at therapeutic doses; this label gives no taper instruction.
After prolonged use expect withdrawal: dysphoria, fatigue, vivid dreams, sleep change, increased appetite, agitation.
Priapism has occurred during withdrawal and planned holidays; mention it before a holiday in an adolescent male.
Drug holidays are reasonable where appetite or growth limits treatment; the growth data make that a first-year conversation. No partial dose exists below 26.1 mg / 5.2 mg.
Pregnancy & Lactation
Pregnancy: No data on Azstarys itself; methylphenidate studies have not identified a drug-associated risk. Stimulants reduce placental perfusion. Delayed fetal ossification in rats at 3 times the maximum human dose.
Lactation: No data on serdexmethylphenidate in milk. For the dexmethylphenidate component, infant doses were 0.16% to 0.7% of the maternal dose. Monitor for agitation, poor feeding and low weight gain.
Dexmethylphenidate specifically: a maternal requirement is not a reason to stop breastfeeding; large doses may interfere before lactation is established. (LactMed 2025)
Exposure Registry: National Pregnancy Registry for Psychostimulants, 1-866-961-2388
Counseling Points
Counsel the family on:
Why the milligram numbers look large: most of the capsule is prodrug, inactive until the gut converts it. The 39.2/7.8 mg capsule equals about 30 mg of dexmethylphenidate.
That no other ADHD medication converts to this one by milligrams, so any substitution must be checked with the prescriber first.
Coverage running to roughly 13 hours, so a late-morning dose still works at bedtime. Keep the dose time fixed and early.
That opening the capsule into water or applesauce is a labelled option, but the mixture must be finished within 10 minutes.
Appetite suppression, largest in the first 4 months: move the largest meal to breakfast and to the evening.
Locked storage, and that sharing a Schedule II medication is a felony.
Advise them to call for:
Chest pain, fainting, or a racing heart that does not settle.
New hallucinations, or new suspicious, fearful or grandiose thinking.
Wheeze, rash or itching after a dose, reported with this product specifically.
Numbness or colour change in the fingers or toes; eye pain or blurred vision.
A new tic, or a marked worsening of an existing one.
Weight loss, or clothes fitting more loosely, particularly in the first 4 months.
A painful erection lasting more than a few hours, including during a planned break.
References
DailyMed. Azstarys (serdexmethylphenidate and dexmethylphenidate) capsules prescribing information. Commave Sub, LLC. 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00b5e716-5564-4bbd-acaf-df2bc45a5663
LactMed. Dexmethylphenidate. Drugs and Lactation Database, NICHD. 2025. https://www.ncbi.nlm.nih.gov/books/NBK500764/
FDA. National Drug Code Directory, openFDA. Queried by generic names serdexmethylphenidate and dexmethylphenidate. 2026. https://api.fda.gov/drug/ndc.json
American Academy of Pediatrics. Clinical practice guideline for the diagnosis, evaluation, and treatment of ADHD in children and adolescents. Pediatrics. 2019. https://publications.aap.org/pediatrics/article/144/4/e20192528/81590/
AHRQ. ADHD diagnosis and treatment in children and adolescents. Comparative Effectiveness Review No. 267. 2024. https://www.ncbi.nlm.nih.gov/books/NBK603001/