Dextroamphetamine

FDA Drug Information • Also known as: Dextroamphetamine, Xelstrym

Brand Names: Dextroamphetamine, Xelstrym
Drug Class: Central Nervous System Stimulant [EPC]
Route: TRANSDERMAL
Dosage Form: PATCH, EXTENDED RELEASE
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: ABUSE, MISUSE, AND ADDICTION XELSTRYM has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including XELSTRYM, can result in overdose and death [see OVERDOSAGE (10) ] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing XELSTRYM, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout XELSTRYM treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction [see WARNINGS AND PRECAUTIONS (5.1) and DRUG ABUSE AND DEPENDENCE (9.2) ] . WARNING: ABUSE, MISUSE, AND ADDICTION See full prescribing information for complete boxed warning. XELSTRYM has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including XELSTRYM, can result in overdose and death ( 5.1 , 9.2 , 10 ): Before prescribing XELSTRYM, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout treatment, reassess each patient’s risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

Description

11 DESCRIPTION XELSTRYM (dextroamphetamine) transdermal system, contains dextroamphetamine, a CNS stimulant. Dextroamphetamine is the dextro isomer of the compound d , l -amphetamine. The chemical name for dextroamphetamine is (2S)-1-phenylpropan-2-amine. It is a clear to slightly amber colored liquid. Molecular weight of dextroamphetamine is 135.21 g/mol and the molecular formula is C 9 H 13 N. The chemical structure is: XELSTRYM is provided in four strengths: 4.5 mg/9 hours, 9 mg/9 hours, 13.5 mg/9 hours, and 18 mg/9 hours. The composition per unit area of all dosage strengths is identical. Inactive ingredients include: acrylic adhesives, green ink, polyester/polyurethane backing, and polyester release liner. Table 4: XELSTRYM (dextroamphetamine) transdermal system Dosage Strength (dextroamphetamine) Dextroamphetamine Content per Transdermal System Transdermal System Size 4.5 mg / 9 hours 5 mg 4.76 cm 2 9 mg / 9 hours 10 mg 9.52 cm 2 13.5 mg / 9 hours 15 mg 14.29 cm 2 18 mg / 9 hours 20 mg 19.05 cm 2 Transdermal System Components XELSTRYM consists of three layers ( Figure 1 ). The layers are (1) oversized protective silicone-coated polyester release liner that is removed and discarded prior to application (2) acrylic adhesive matrix containing dextroamphetamine, and (3) polyester and polyurethane laminate film (backing). Figure 1: XELSTRYM Transdermal System (Exploded View) chemical structure Figure1

What Is Dextroamphetamine Used For?

1 INDICATIONS AND USAGE XELSTRYM ® is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older [see CLINICAL STUDIES (14) ] . Limitations of Use The use of XELSTRYM is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage [see Warnings and Precautions (5.5) , Use in Specific Populations (8.4) ]. XELSTRYM is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older ( 1 ) Limitations of Use: The use of XELSTRYM is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage ( 5.5 , 8.4 ).

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Pediatric patients (6 to 17 years): Recommended starting dose is 4.5 mg/9 hours. Titrate dosage in weekly increments of 4.5 mg up to a maximum recommended dose of 18 mg/9 hours ( 2.2 ) Adults: Recommended starting dose is 9 mg/9 hours. Maximum recommended dose is 18 mg/9 hours ( 2.2 ) Apply one XELSTRYM transdermal system 2 hours before an effect is needed and remove within 9 hours ( 2.3 ) Apply XELSTRYM to one of the following sites: hip, upper arm, chest, upper back or flank. Change the site of application when applying a new transdermal system ( 2.3 ) Do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine base compositions and differing pharmacokinetic profiles ( 2.5 ) Severe renal impairment: Maximum recommended dose is 13.5 mg/9 hours ( 2.6 ) End stage renal disease (ESRD): Maximum recommended dose is 9 mg/9 hours ( 2.6 ) 2.1 Pretreatment Screening Prior to treating patients with XELSTRYM, assess: for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see WARNINGS AND PRECAUTIONS (5.2) ] . the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating XELSTRYM [see WARNINGS AND PRECAUTIONS (5.11) ] . 2.2 Recommended Dosage Pediatric Patients 6 to 17 years Recommended starting dose of XELSTRYM in pediatric patients 6 to 17 years is 4.5 mg/9 hours. Dosage may be adjusted in weekly increments of 4.5 mg up to a maximum recommended dose of 18 mg/9 hours. Adults Recommended starting dose of XELSTRYM in adults is 9 mg/9 hours. Dosage may be adjusted up to a maximum recommended dose of 18 mg/9 hours. Apply XELSTRYM to the application site 2 hours before an effect is needed and remove within 9 hours after application. Dose titration and final dosage should be individualized depending on clinical response and tolerability. 2.3 Important Administration Instructions Apply one XELSTRYM transdermal system at a time for not more than 9 hours. Use only one XELSTRYM per 24 hours. Apply XELSTRYM to clean (void of lotions, oils, or gels), dry (not wet), and intact skin at the selected application site. Application sites include: hip, upper arm, chest, upper back, or flank. Select a different application site each time a new XELSTRYM transdermal system is applied [see WARNINGS AND PRECAUTIONS (5.9) ] . Avoid touching the adhesive side of XELSTRYM in order to avoid absorption of amphetamine. If the adhesive side is touched, immediately wash hands with soap and water. If the XELSTRYM transdermal system lifts at the edges, reattach XELSTRYM by pressing firmly and smoothing down the edges of the system. If XELSTRYM comes off completely, apply a new XELSTRYM transdermal system. XELSTRYM should not be applied or re-applied with dressings, tape or other common adhesives. Avoid exposing the application site to direct external heat...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling Known hypersensitivity to amphetamine products or other ingredients of XELSTRYM [see CONTRAINDICATIONS (4) ] Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see CONTRAINDICATIONS (4) and DRUG INTERACTIONS (7.1) ] Abuse, Misuse, and Addiction [see BOXED WARNING, WARNINGS AND PRECAUTIONS (5.1) and DRUG ABUSE AND DEPENDENCE (9.2, 9.3) ] Risks to Patients with Serious Cardiac Disease [see WARNINGS AND PRECAUTIONS (5.2) ] Increased Blood Pressure and Heart Rate [see WARNINGS AND PRECAUTIONS (5.3) ] Psychiatric Adverse Reactions [see WARNINGS AND PRECAUTIONS (5.4) ] Long-Term Suppression of Growth in Pediatric Patients [see WARNINGS AND PRECAUTIONS (5.5) ] Peripheral Vasculopathy, including Raynaud's phenomenon [see WARNINGS AND PRECAUTIONS (5.6) ] Serotonin Syndrome [see WARNINGS AND PRECAUTIONS (5.7) ] Contact Sensitization [see WARNINGS AND PRECAUTIONS (5.8) ] Application Site Reactions [see WARNINGS AND PRECAUTIONS (5.9) ] Use of External Heat [see WARNINGS AND PRECAUTIONS (5.10) ] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see WARNINGS AND PRECAUTIONS (5.11) ] Most common adverse reactions (incidence ≥2% and greater than the rate for placebo) in pediatric patients 6 to 17 years treated with XELSTRYM were decreased appetite, headache, insomnia, tic, abdominal pain, vomiting, nausea, irritability, blood pressure increased, and heart rate increased ( 6.1 ) Most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) in adults treated with lisdexamfetamine were decreased appetite, insomnia, dry mouth, diarrhea, nausea, and anxiety ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Noven Therapeutics, LLC at 1-877-567-7857 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of XELSTRYM for the treatment of ADHD in adults and pediatric patients 6 to 17 years is based on a study with XELSTRYM in pediatric patients (presented below) and adequate and well-controlled studies of lisdexamfetamine in adult and pediatric patients with ADHD. XELSTRYM was studied in pediatric patients 6 to 17 years with ADHD. The safety data are from a 7-week study including a 5-week open-label dose optimization phase (n=110) followed by a 2-week randomized, parallel-group, crossover, placebo-controlled double-blind treatment phase (n=105) [see CLINICAL TRIALS (14) ] . Adverse Reactions Leading to Discontinuation of Treatment In the dose-optimization phase (no placebo comparator in this phase), 2.7% (3/110) of patients treated with XELSTRYM discontinued due to adverse reactions. These adverse reactions reported in one patient each were abdominal pain (0.9%), irritability (0.9%) and decreased appetite (0.9%). There were no discontinuations due to adverse reactions during the double-blind phase. Adverse Reactions Occurring at an Incidence of 5% or More in XELSTRYM Treated Pediatric Patients Ages 6 to 17 Years During Dose-optimized Treatment Adverse reactions (incidence of ≥ 5%) that occurred during the dose-optimization phase of the clinical study include: decreased appetite (54%), insomnia 1 (32%), headache (21%), irritability (16%), abdominal pain 2 (16%) affect lability 3 (16%), application site pain 4 (13%), nausea (9%), application site pruritus (7%), and fatigue (5%). 1 insomnia includes insomnia, delayed sleep phase, initial insomnia, middle insomnia, and terminal insomnia 2 abdominal pain includes abdominal pain and abdominal pain upper 3 affect lability includes affect lability, emotional disorder, mood swings, and mood altered 4 application site pain...

Drug Interactions

7 DRUG INTERACTIONS Acidifying and Alkalinizing Agents: Agents that alter GI and urinary pH can alter blood levels of amphetamine. Acidifying agents can decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels ( 2.7 , 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Amphetamine Table 3: Drugs Having Clinically Important Interactions with Amphetamines MAO Inhibitors (MAOI) Clinical Impact MAOI antidepressants slow amphetamine metabolism, increasing amphetamine’s effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Intervention Do not administer XELSTRYM during or within 14 days following the administration of MAOI [see CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.7) ]. Serotonergic Drugs Clinical Impact The concomitant use of XELSTRYM and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during XELSTRYM initiation or dosage increase. If serotonin syndrome occurs, discontinue XELSTRYM and the concomitant serotonergic drug(s) [see WARNINGS AND PRECAUTIONS (5.7) ] . CYP2D6 Inhibitors Clinical Impact The concomitant use of XELSTRYM and CYP2D6 inhibitors may increase the exposure of XELSTRYM compared to the use of the drug alone, and increase the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during XELSTRYM initiation and after a dosage increase. If serotonin syndrome occurs, discontinue XELSTRYM and the CYP2D6 inhibitor [see WARNINGS AND PRECAUTIONS (5.7) and OVERDOSAGE (10) ]. Alkalinizing Agents Clinical Impact Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Intervention Co-administration of XELSTRYM and urinary alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Urinary acidifying agents can lower blood levels and efficacy of amphetamines. Intervention Increase dose based on clinical response. Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of dextroamphetamine in the brain; cardiovascular effects can be potentiated. Intervention Monitor frequently and adjust or use alternative therapy based on clinical response. 7.2 Drugs Having No Clinically Important Interactions with Amphetamine From a pharmacokinetic perspective, no dose adjustment of XELSTRYM is necessary when XELSTRYM is co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when XELSTRYM is co-administered [see CLINICAL PHARMACOLOGY (12.3) ]. From a...

Contraindications

4 CONTRAINDICATIONS XELSTRYM is contraindicated in patients: with known hypersensitivity to amphetamine products or other components of XELSTRYM. Anaphylactic reactions, Stevens-Johnson Syndrome, angioedema, and urticaria have been observed in postmarketing reports [see ADVERSE REACTIONS (6.2) ] taking monoamine oxidase inhibitors (MAOI), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis [see WARNINGS AND PRECAUTIONS (5.7) and DRUG INTERACTIONS (7.1) ] Known hypersensitivity to amphetamine products or other ingredients in XELSTRYM ( 4 ) Use with monoamine oxidase inhibitor (MAOI), or within 14 days of the last MAOI dose ( 4 , 7.1 )

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including XELSTRYM, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/adhd-medications/. Risk Summary Available data from published epidemiologic studies and postmarketing reports on use of prescription amphetamine in pregnant women have not identified a drug-associated risk of major birth defects and miscarriage (see DATA ). Adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers taking amphetamines during pregnancy [see CLINICAL CONSIDERATIONS ]. No apparent effects on morphological development were observed in embryo-fetal development studies, with oral administration of amphetamine to rats and rabbits during organogenesis. However, in a pre- and post-natal development study, amphetamine ( d - to l - ratio of 3:1) administered orally to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of amphetamine. In addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with amphetamine. Long-term neurochemical and behavioral effects have also been reported in animal developmental studies using clinically relevant doses of amphetamine (see DATA ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies...

Overdosage

10 OVERDOSAGE Clinical Effects of Overdose Overdose of CNS stimulants is characterized by the following sympathomimetic effects: Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop. CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop. Overdose Management Consider the possibility of multiple drug ingestion. Dextroamphetamine is not dialyzable. Remove all transdermal systems immediately and cleanse the area(s) to remove any remaining adhesive. The continuing absorption of dextroamphetamine from the skin, even after removal of the transdermal system, should be considered when treating patients with overdose. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied XELSTRYM (dextroamphetamine) transdermal system is a translucent product with a printed backing on one side and a release liner on the other packaged in an individual pouch supplied as: 4.5 mg/9 hours transdermal system (system size: 4.76 cm 2 ) Carton of 30 transdermal systems, each transdermal system is packaged in an individual pouch NDC 68968-0205-3 9 mg/9 hours transdermal system (system size: 9.52 cm 2 ) Carton of 30 transdermal systems, each transdermal system is packaged in an individual pouch NDC 68968-0210-3 13.5 mg/9 hours transdermal system (system size: 14.29 cm 2 ) Carton of 30 transdermal systems, each transdermal system is packaged in an individual pouch NDC 68968-0215-3 18 mg/9 hours transdermal system (system size: 19.05 cm 2 ) Carton of 30 transdermal systems, each transdermal system is packaged in an individual pouch NDC 68968-0220-3 Storage and Handling Store at 68°F to 77° F (20°C to 25° C); excursions permitted between 15°C to 30° C (59 to 86° F) [see USP Controlled Room Temperature]. Protect from light. Store XELSTRYM in the individual sealed pouch until use. Apply immediately upon removal from the protective pouch.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.