Xelstrym

(dextroamphetamine)
Xelstrym (dextroamphetamine); CII
Full Prescribing Information
DailyMed Drug Information
Summary
Xelstrym is a dextroamphetamine transdermal system, the only amphetamine patch on the U.S. market, approved for ADHD from age 6 and worn up to 9 hours a day. It delivers single-entity d-amphetamine through the skin, bypassing swallowing and letting a caregiver end the exposure early by removing the patch. That reversibility is its differentiator; its cost is the skin, where irritation and discomfort were near-universal. Schedule II; brand only.
Forms & Strengths
Transdermal system (9 hour wear; dose set by patch area): 4.5 mg/9 h, 9 mg/9 h, 13.5 mg/9 h, 18 mg/9 h
Dosing
Age: ≥ 6 y/o
Onset: ~ 2 hours
Duration: up to 12 hours
Release Profile: continuous transdermal delivery, about 90% of content over 9 hours; peak plasma at 6 to 9 hours, ~6 hours on repeat
Initial Dose:
6-17 y/o: 4.5 mg/9 h daily
≥ 18 y/o: 9 mg/9 h daily
Titration: 4.5 mg/9 h every 7 days, patients 6-17
Max Dose:
All ages: 18 mg/9 h, one system per 24 hours
Severe renal impairment, GFR 15 to under 30 mL/min/1.73 m²: 13.5 mg/9 h
End-stage renal disease, GFR under 15 mL/min/1.73 m²: 9 mg/9 h
Considerations: Apply 2 hours before effect is needed, remove within 9 hours, and use a shorter wear to shorten the day. Rotate sites daily, never cut a patch, and keep external heat off it.
Pharmacology
Mechanism: Blocks reuptake at DAT and NET and promotes presynaptic catecholamine release via VMAT2 and TAAR1; the release component distinguishes amphetamines from methylphenidate
Delivery / Release: Dextroamphetamine in an acrylic adhesive matrix; absorption tracks wear time and area, not site, with 20% to 30% variability
Formulation: d-isomer only, unlike Adderall or Evekeo
Metabolism: CYP2D6, polymorphic, forms active 4-hydroxyamphetamine. Half-life after a 9 hour wear is 6.4 h in children, 11.5 h in adults; not dialyzable, hence the ESRD cap
Class Positioning: the only amphetamine whose exposure can be curtailed mid-day; the cost is daily adhesive on skin and a 1.5-fold rise under heat. Daytrana is methylphenidate, not interchangeable
Indications
ADHD (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients ≥ 6 y/o
Off-Label Uses
None established for this formulation by graded pediatric evidence.
Where the evidence does not support use:
Children under 6: argued against by this label.
Wear beyond 9 hours: a dose increase without a dose change.
Cutting a patch: forbidden.
Non-ADHD indications, and cognitive enhancement without ADHD: AHRQ CER 267 graded none (AHRQ 2024).
Contraindications & Warnings
Boxed Warning: Abuse, misuse, and addiction. High abuse potential leading to substance use disorder; overdose and death, more so at higher doses. Assess risk before prescribing; reassess throughout.
Contraindicated:
Known hypersensitivity to amphetamine or components
MAOI use, current or within 14 days, including linezolid and IV methylene blue
Contact sensitization: suspect it if erythema comes with edema, papules or vesicles that fail to improve within 48 hours or spread beyond the site. Discontinue.
Its consequence is not local: a sensitized patient may be unable to take amphetamine in ANY form.
Use with caution (Warnings, not contraindications):
Structural cardiac abnormality, cardiomyopathy, serious arrhythmia or coronary disease; label says avoid
Hypertension; psychosis; bipolar disorder; tics or Tourette syndrome; Raynaud phenomenon
Dermatitis, eczema or fragile skin at candidate sites
Regular external heat at the site (see Interactions)
Severe renal impairment and ESRD, capping the dose at 13.5 and 9 mg/9 h
Substance use disorder in the household; a worn patch is removable by anyone
Screen before starting: cardiac and family cardiac history with exam; tic history; skin at candidate sites and any prior adhesive reaction.
Also screen: renal function, which sets the ceiling; abuse and diversion risk; baseline height, weight, BP, HR.
Drug Interactions
MAOIs (also linezolid, IV methylene blue): hypertensive crisis. Confirm a 14 day washout before the first patch.
Serotonergic agents (SSRIs, SNRIs, TCAs, triptans, lithium, tramadol): serotonin syndrome. Start lower; remove the patch and stop the other agent if symptoms appear.
CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine): raise exposure and serotonin syndrome risk. Prefer an alternative; else start lower.
Urinary pH agents: acidifiers lower levels; alkaline urine raises exposure. Adjust strength by clinical response.
External heat is a pharmacokinetic interaction: a heating pad over the system for 6 hours raised Cmax to about 116% and AUC to about 150%. Instruct explicitly against it.
Sympathomimetics: additive cardiovascular effect; avoid OTC decongestants.
Administration
One system per 24 hours, applied 2 hours before effect is needed and removed within 9 hours.
Early removal is a legitimate dose adjustment: absorption tracks wear time, so it answers an evening appetite or sleep problem.
Clean, dry, intact skin free of lotion or oil: hip, upper arm, chest, upper back or flank. Rotate daily; 28 days on one adult site raised Cmax 86% against 46% with rotation.
Avoid touching the adhesive side. Press a lifting edge down, replace one that falls off, and never tape, cut or trim.
A used system still contains drug; dispose of it as a Schedule II item.
From any other amphetamine: stop the previous drug and titrate from the starting strength.
Side Effects
Common, 6-17, dose optimization: decreased appetite 54%, insomnia 32%, headache 21%, irritability, abdominal pain and affect lability 16% each, site pain 13%, nausea 9%, fatigue 5%.
Application site reactions are near-universal and are the defining tolerability issue: at double-blind clinic assessment, irritation 94% vs 54% placebo, any discomfort 69% vs 9%, severe 10% vs 4%.
What to tell them: pain, itch, burning, erythema and edema during or just after wear; discomfort resolves in 2 to 4 hours, and nobody in the pediatric study stopped for it.
Serious:
Contact sensitization, which may end the ability to take amphetamine in any form.
Sudden death with structural cardiac abnormality or serious cardiac disease; avoid rather than monitor.
Psychosis or mania, roughly 0.1% in pooled stimulant trials, and serotonin syndrome; remove the patch, stop any serotonergic agent, consider discontinuing.
Anaphylaxis, angioedema, urticaria, Stevens-Johnson syndrome; stop and do not rechallenge.
Peripheral vasculopathy with digital ulceration; growth suppression, mean weight falling over the 7 week trial; new or worsening tics, 2% vs 0%.
Monitoring & Labs
Application sites: inspect at every visit and at 2 weeks, when irritation peaks; ask whether a site is being reused.
Contact sensitization: apply the criteria above at any visit where erythema is reported.
Cardiovascular: HR and BP at baseline, each dose change, and every 6 months.
Growth, appetite and sleep: height, weight and BMI charted at baseline and every 6 months; appetite and sleep every visit. The first response to insomnia is earlier removal.
Psychiatric and tics: psychosis, mania, aggression, affect lability and tics at each visit and 2 weeks after any increase; inspect the digits.
Renal function: at baseline and whenever GFR could change, since the ceiling drops to 13.5 then 9 mg/9 h.
Abuse and diversion: adherence, patch counts and PDMP check at each refill; used patches retain drug. No routine labs.
Discontinuation & Taper
Can be stopped abruptly; no taper required.
Offset is not immediate on removal; half-life after a 9 hour wear is 6.4 h in children, up to 11.5 h in adults.
Physical dependence is labelled; withdrawal is dysphoria, depression, fatigue, vivid dreams, sleep change, increased appetite.
Drug holidays are easy: a holiday is a day without a patch.
If stopped for contact sensitization, do not simply switch to an oral amphetamine. Some sensitized patients cannot take amphetamine at all.
Pregnancy & Lactation
Pregnancy: Published data have not identified a drug-associated risk of major birth defects or miscarriage; background risk is 2% to 4% and 15% to 20%.
Pregnancy, clinical: amphetamines vasoconstrict, may reduce placental perfusion and stimulate contractions; premature delivery and low birth weight are reported.
Neonate: monitor for withdrawal: feeding difficulty, irritability, agitation, drowsiness.
Lactation: in milk at relative infant doses of 2% to 13.8%, milk to plasma 1.9 to 7.5; the label does not recommend breastfeeding.
Lactation, dextroamphetamine: four mothers on a mean 18 mg daily gave a median milk level of 219 mcg/L, 5.7% of the maternal dose, with all four infants normal. (LactMed 2025)
Exposure Registry: National Pregnancy Registry for Psychiatric Medications, ADHD arm, 1-866-961-2388, https://womensmentalhealth.org/research/pregnancyregistry/adhd-medications/
Counseling Points
Counsel the family on:
That the skin under the patch will almost certainly be red, often itchy or stinging, and that this is expected rather than an allergy.
The numbers, out loud: most children had irritation, about one in ten severely, and none stopped for it. Warned in advance, families get through week one.
That discomfort settles within 2 to 4 hours; apply 2 hours before it is needed, so before breakfast on a school morning.
Daily site rotation, since reusing one spot hurts more and delivers more drug.
That early removal shortens the day, but effect fades over hours rather than at removal.
No heat over the patch, no touching the sticky side, and never cutting one.
That a used patch still contains medication and is disposed of as a controlled substance.
Advise them to call for:
Redness under the patch with swelling, bumps or blisters, or that does not settle within two days or spreads outside the outline; any rash elsewhere on the body.
Chest pain on exertion, fainting, or a racing heart that does not settle.
New hallucinations, or new suspicious or fearful thinking.
Numbness or colour change in the fingers or toes; a new tic; weight loss; a patch that fell off and cannot be found.
References
DailyMed. Xelstrym (dextroamphetamine) transdermal system prescribing information. Noven Therapeutics. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0862f02a-72a8-41cc-8845-57cf4974bb6f
FDA. openFDA National Drug Code Directory, generic_name "dextroamphetamine". 2026. https://api.fda.gov/drug/ndc.json?search=generic_name:%22dextroamphetamine%22&limit=1000
LactMed. Dextroamphetamine. Drugs and Lactation Database, NICHD. 2025. https://www.ncbi.nlm.nih.gov/books/NBK501740/
AHRQ. ADHD Diagnosis and Treatment in Children and Adolescents. Comparative Effectiveness Review No. 267. 2024. https://www.ncbi.nlm.nih.gov/books/NBK603001/