Important Safety Information

Indication

ADZENYS XR-ODT is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older.

Limitations of Use

The use of ADZENYS XR-ODT 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.

WARNING: ABUSE, MISUSE, AND ADDICTION

ADZENYS XR-ODT 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 ADZENYS XR-ODT, can result in overdose and death, and this risk is increased with higher doses of unapproved methods of administration, such as snorting or injection.

Before prescribing ADZENYS XR-ODT, 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 ADZENYS XR-ODT treatment, reassess each patient’s risk for abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

Contraindications

In patients known to be hypersensitive to amphetamine, or other components of ADZENYS XR-ODT. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products.
Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis.

Warnings and Precautions

Abuse, Misuse, and Addiction: ADZENYS XR-ODT has a high potential for abuse and misuse. The use of ADZENYS XR-ODT exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. ADZENYS XR-ODT can be diverted for non-medical use into illicit channels or distribution. Misuse and abuse of CNS stimulants, including ADZENYS XR-ODT, can result in overdose and death, and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing ADZENYS XR-ODT, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, and proper disposal of any unused drug. Advise patients to store ADZENYS XR-ODT in a safe place, preferably locked, and instruct patients not to give ADZENYS XR-ODT to anyone else. Throughout ADZENYS XR-ODT treatment, reassess each patient’s risk for abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Risks to Patients with Serious Cardiac Disease: Sudden death has occurred in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosages. Avoid ADZENYS XR-ODT use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
Increased Blood Pressure and Heart Rate: CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mm Hg) and heart rate (mean increase approximately 3 to 6 bpm). Some patients may have larger increases. Monitor all ADZENYS XR-ODT-treated patients for potential tachycardia and hypertension.
Psychiatric Adverse Reactions: Exacerbation of Pre-Existing Psychosis CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating ADZENYS XR-ODT treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression). New Psychotic or Manic Symptoms CNS stimulants, at the recommended dosage, may cause psychotic or manic symptoms (e.g. hallucinations, delusional thinking or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0% of placebo-treated patients. If such symptoms occur, consider discontinuing ADZENYS XR-ODT.
Long-Term Suppression of Growth in Pediatric Patients: ADZENYS XR-ODT is not approved for use and is not recommended in pediatric patients below 6 years of age. CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in ADZENYS XR-ODT-treated pediatric patients treated with CNS stimulants. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted.
Peripheral Vasculopathy, Including Raynaud’s Phenomenon: CNS stimulants, including ADZENYS XR-ODT, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports and at therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during ADZENYS XR-ODT treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for ADZENYS XR-ODT-treated patients who develop signs or symptoms of peripheral vasculopathy.
Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: CNS stimulants, including amphetamine, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported. Before initiating ADZENYS XR-ODT, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor ADZENYS XR-ODT-treated patients for the emergence or worsening of tics or Tourette’s syndrome and discontinue treatment if clinically appropriate.
Potential for Overdose Due to Medication Errors: Medication errors, including substitution and dispensing errors, between ADZENYS XR-ODT and other amphetamine products could occur, leading to possible overdosage. To avoid substitution errors and overdosage, do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine base compositions and differing pharmacokinetic profiles.

Adverse Reactions

Common side effects of ADZENYS XR-ODT in children 6 to 12 years of age also include:
- Abdominal pain
- Fever
- Infection
- Accidental injury
- Asthenia
- Loss of appetite
- Vomiting
- Nausea
- Dyspepsia
- Insomnia
- Emotional lability
- Nervousness
- Dizziness
- Weight loss

Common side effects of ADZENYS XR-ODT in children 13 to 17 years of age also include:
- Abdominal pain
- Loss of appetite
- Insomnia
- Weight loss

Common side effects of ADZENYS XR-ODT in adults also include:
- Headache
- Loss of appetite
- Insomnia
- Dizziness
- Urinary tract infection
- Asthenia
- Nausea
- Agitation
- Tachycardia
- Dry mouth
- Diarrhea
- Anxiety
- Weight loss

To report SUSPECTED ADVERSE REACTIONS, contact Neos Therapeutics, Inc. at 1-888-319-1789 or http://www.adzenysxrodt.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

Monoamine Inhibitors (MAOI): MAOI antidepressants slow amphetamines effect on the release of norepinephrine and other monoamine from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Do not administer ADZENYS XR-ODT during or within 14 days following administration of MAOI.
Serotonergic Drugs: The concomitant use of ADZENYS XR-ODT and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during ADZENYS XR-ODT initiation or dosage increase. If serotonin syndrome occurs, discontinue ADZENYS XR-ODT and the concomitant serotonergic drug(s).
Alkalinizing Agents: Increase blood levels and potentiate the action of amphetamine. Co-administration of ADZENYS XR-ODT and gastrointestinal alkalinizing agents should be avoided.
Acidifying Agents: Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response.
Tricyclic Antidepressants: May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Monitor frequently and adjust or use alternative therapy based on clinical response.

Pregnancy and Lactation

Available data from epidemiologic studies and postmarketing reports on the use of amphetamine in pregnant women over decades of use have not identified a drug-associated risk of major birth defects or miscarriage. Neonates exposed to amphetamine in utero are at risk for withdrawal symptoms following delivery. Adverse pregnancy outcomes include premature delivery and low birth weight have been seen in infants born to mothers taking amphetamines during pregnancy. Monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness.
There are no reports of adverse effects on the breastfed infant. Long-term neurodevelopment effects on infants from amphetamine exposure are unknown. It is possible that large dosages of amphetamine might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in nursing infants, advise patients that breastfeeding is not recommended during treatment with ADZENYS XR-ODT.

Pediatric Use

The safety and effectiveness of ADZENYS XR-ODT have not been established in pediatric patients below the age of 6 years.
In studies evaluating extended-release amphetamine products, patients 4 to <6 years of age had higher systemic amphetamine exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had higher incidence of adverse reactions, including weight loss.

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