WARNING: ABUSE, MISUSE, AND ADDICTION
ARYNTA 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 ARYNTA, 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 ARYNTA, 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 ARYNTA 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), Drug Abuse and Dependence (9.2)].
Abuse, Misuse, and Addiction: ARYNTA has a high potential for abuse and misuse. The use of ARYNTA exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. ARYNTA can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence (9.2)]. Misuse and abuse of CNS stimulants, including ARYNTA, 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 ARYNTA, 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 ARYNTA in a safe place, preferably locked, and instruct patients to not give ARYNTA to anyone else. Throughout ARYNTA treatment, reassess each patient's risk of 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 been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage. Avoid ARYNTA 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 about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Some patients may have larger increases.
Monitor all ARYNTA-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. Prior to initiating ARYNTA 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, and 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 ARYNTA.
Long-Term Suppression of Growth in Pediatric Patients: ARYNTA is not approved for use and is not recommended in pediatric patients below 6 years of age [see Use in Specific Populations (8.4)].
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.
In a 4-week, placebo-controlled trial of ARYNTA in pediatric patients ages 6 to 12 years old with ADHD, there was a dose-related decrease in weight in the ARYNTA groups compared to weight gain in the placebo group. Additionally, in studies of another stimulant, there was slowing of the increase in height [see Adverse Reactions (6.1)].
Closely monitor growth (weight and height) in ARYNTA-treated pediatric patients. Patients who are 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 ARYNTA, 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 the 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 ARYNTA treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for ARYNTA-treated patients who develop signs or symptoms of peripheral vasculopathy.
Serotonin Syndrome: Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort [see Drug Interactions (7.1)]. The co-administration with cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with increased exposure to the active metabolite of ARYNTA (dextroamphetamine). In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions (7.1)].
Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Concomitant use of ARYNTA with MAOI drugs is contraindicated [see Contraindications (4)].
Discontinue treatment with ARYNTA and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment. If concomitant use of ARYNTA with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate ARYNTA with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.
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 [see Adverse Reactions (6.2)].
Before initiating ARYNTA, assess the family history and clinically evaluate patients for tics or Tourette's syndrome. Regularly monitor ARYNTA-treated patients for the emergence or worsening of tics or Tourette's syndrome, and discontinue treatment if clinically appropriate.
