Introduction
Xelstrym (dextroamphetamine) transdermal system is a central nervous system stimulant approved by the FDA in 2022 for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older. It represents the first and only dextroamphetamine transdermal system available, offering an alternative delivery method to traditional oral stimulant formulations.
Mechanism of Action
Xelstrym contains dextroamphetamine, a sympathomimetic amine with CNS stimulant activity. The exact mechanism of action in ADHD is not fully established, but it is believed to work primarily by blocking the reuptake of norepinephrine and dopamine into presynaptic neurons and facilitating the release of these monoamines into extraneuronal space. This action increases the availability of these neurotransmitters in synaptic clefts, particularly in brain regions responsible for attention, focus, and impulse control.
Indications
Xelstrym is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older. Clinical studies have demonstrated efficacy in improving both inattention and hyperactivity/impulsivity symptoms as measured by standardized ADHD rating scales.
Dosage and Administration
Initial Dose: Apply one 4.5 mg/9-hour patch daily in patients 6-17 years; apply one 9 mg/9-hour patch daily in patients 18 years and older Titration: May increase dose in increments of 4.5 mg at weekly intervals Maximum Dose: 18 mg/9 hours (13.5 mg/9 hours for patients 6-12 years; 18 mg/9 hours for patients 13 years and older) Administration: Apply to clean, dry, intact skin on the hip, abdomen, upper arm, or shoulder. Rotate application sites. Wear for 9 hours and remove promptly after wearing period. Special Populations: Renal impairment: Use with caution. Hepatic impairment: Use with caution. Geriatric: Not studied. Pediatric: Safety established for ages 6-17.Pharmacokinetics
Absorption: Systemic absorption occurs through transdermal delivery. Peak concentrations typically achieved within 8 hours of application. Bioavailability approximately 78% relative to oral dextroamphetamine. Distribution: Volume of distribution: 3.3±1.0 L/kg. Protein binding: 15-20%. Metabolism: Hepatic metabolism via cytochrome P450 2D6 with subsequent glucuronidation. Dextroamphetamine is metabolized to active metabolites including hydroxyamphetamine and norephedrine. Elimination: Terminal half-life: 11-12 hours. Excretion: Primarily renal (30-40% unchanged); urinary excretion is pH-dependent with acidic urine promoting elimination.Contraindications
- Known hypersensitivity to amphetamine products or adhesive component
- Patients with advanced arteriosclerosis
- Symptomatic cardiovascular disease
- Moderate to severe hypertension
- Hyperthyroidism
- Glaucoma
- Agitated states
- History of drug abuse
- Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of MAOI use
Warnings and Precautions
Boxed Warning: High potential for abuse and dependence. Use with caution in patients with history of drug abuse. Cardiovascular: May increase blood pressure and heart rate. Monitor regularly. Psychiatric: May exacerbate psychotic symptoms in patients with pre-existing psychosis. May induce manic episodes in bipolar disorder. Monitor for new or worsening aggressive behavior or hostility. Growth Suppression: Monitor height and weight in pediatric patients. Peripheral Vasculopathy: Raynaud's phenomenon has been reported. Serotonin Syndrome: Risk when used with other serotonergic drugs. Skin Reactions: May cause contact dermatitis or skin irritation at application site.Drug Interactions
MAO Inhibitors: Contraindicated due to risk of hypertensive crisis Acidifying Agents: Ammonium chloride, ascorbic acid may decrease amphetamine levels Alkalinizing Agents: Sodium bicarbonate, acetazolamide may increase amphetamine levels Adrenergic Blockers: Amphetamines may inhibit antihypertensive effects Antidepressants: Increased risk of serotonin syndrome with SSRIs, SNRIs, TCAs Antipsychotics: May inhibit antipsychotic efficacy CYP2D6 Inhibitors: May increase dextroamphetamine exposureAdverse Effects
Common (≥5%): Application site reactions (erythema, pruritus, rash), insomnia, decreased appetite, headache, abdominal pain, nausea, vomiting, anxiety, irritability Serious: Cardiovascular events (sudden death, stroke, MI), psychiatric events (psychosis, mania), growth suppression, peripheral vasculopathy, serotonin syndromeMonitoring Parameters
- Blood pressure and heart rate at baseline and regularly during treatment
- Height and weight in pediatric patients (plot on growth charts)
- Psychiatric symptoms assessment
- Signs of misuse or abuse
- Application site evaluation
- ADHD symptom assessment using standardized scales
- Nutritional status
Patient Education
- Apply patch to clean, dry, intact skin each morning and remove after 9 hours
- Rotate application sites daily to minimize skin irritation
- Do not cut patches
- Wash hands after application and removal
- Proper storage and disposal to prevent accidental exposure or misuse
- Report chest pain, palpitations, new psychiatric symptoms, or skin reactions
- Avoid excessive heat exposure to application site (may increase drug delivery)
- Inform healthcare providers of all medications being taken
- Adhere to prescribed wearing time to minimize insomnia
- Maintain regular meal patterns despite possible appetite suppression
References
1. FDA Approval Package: Xelstrym (dextroamphetamine) transdermal system. 2022 2. Childress A, et al. Efficacy and safety of dextroamphetamine transdermal system in children with ADHD. J Child Adolesc Psychopharmacol. 2022;32(3):154-163 3. Xelstrym [package insert]. Bryn Mawr, PA: Noven Pharmaceuticals; 2023 4. Goodman DW, et al. A randomized controlled trial of dextroamphetamine transdermal system in adults with ADHD. CNS Drugs. 2022;36(5):527-539 5. Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2013 6. Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921