New Psychotic or Manic Symptoms: CNS stimulants, at recommended doses, 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 with 0% of placebo-treated patients. If such symptoms occur, consideration discontinuing dextroamphetamine sulfate.

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients, including dextroamphetamine sulfate. Closely monitor growth (weight and height) in Dextroamphetamine Sulfate Oral Solution-treated pediatric patients treated with CNS stimulants.

Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted (see PRECAUTIONS, PEDIATRIC USE).

Seizures: There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Peripheral Vasculopathy, Including Raynaud's Phenomenon: Stimulants, including dextroamphetamine sulfate oral solution, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulcerations 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 dextroamphetamine sulfate oral solution-treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for dextroamphetamine sulfate oral solution-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]. The coadministration with cytochrome P450 (CYP2D6) inhibitors may also increase the risk with increased exposure to dextroamphetamine sulfate oral solution. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions].

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 dextroamphetamine sulfate oral solution with MAOI drugs is contraindicated [see CONTRAINDICATIONS].

Discontinue treatment with dextroamphetamine sulfate oral solution and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of dextroamphetamine sulfate oral solution with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate dextroamphetamine sulfate oral solution 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.