Centanafadine

SIMTRIYO is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients 6 years of age and older weighing at least 20 kg. Limitations of Use The use of SIMTRIYO is not recommended in pediatric patients: Younger than 6 years of age because this pediatric subpopulation had a higher incidence of weight loss than pediatric patients 6 years of age and older. Weighing less than 20 kg because of a lack of data for this subpopulation and the risk of weight loss. SIMTRIYO is a norepinephrine-dopamine-serotonin reuptake inhibitor and central nervous system stimulant indicated for the treatment of ADHD in adults and pediatric patients 6 years of age and older weighing at least 20 kg.

Centanafadine has inhibitory activity at norepinephrine (NE), dopamine (DA), and serotonin (5-HT) reuptake transporters and is a central nervous system stimulant. The mechanism of action of centanafadine in the treatment of ADHD is unclear, however, its efficacy could be mediated through its activity as a norepinephrine-dopamine-serotonin reuptake inhibitor.

Prior to initiating SIMTRIYO, assess: Risk of abuse, misuse, and addiction. For presence of cardiac disease. Heart rate and blood pressure. Risk for developing a manic episode. Family history of tics or Tourette's syndrome and clinically evaluate patients for motor or verbal tics or Tourette's syndrome. Pediatric Patients Aged: 6 to 12 years: Recommended oral dosage is based on weight. 13 to 17 years: Recommended dosage is 280 mg orally once daily. Adults: Recommended starting dosage is 210 mg orally once daily. Dosage may be increased to maximum daily dosage of 280 mg once daily based on clinical response and tolerability. Administer in the morning with or without food, at approximately the same time each day. Capsules may be swallowed whole or opened and entire contents sprinkled on applesauce or yogurt, or in orange juice.

SIMTRIYO is contraindicated in patients: With known hypersensitivity to centanafadine or any of the excipients of SIMTRIYO. Hypersensitivity reactions, including angioedema and anaphylaxis, have been reported with SIMTRIYO. Taking, or within 14 days of stopping, MAOIs due to the risk of serious and possibly fatal drug interactions, including hypertensive crisis and serotonin syndrome. With pheochromocytoma or a history of pheochromocytoma. Serious reactions, including elevated blood pressure and tachyarrhythmia, have been reported in patients with pheochromocytoma or a history of pheochromocytoma who received a CNS stimulant.

Boxed warning: Suicidal Ideation and Behaviors in Pediatric Patients 6 Years of Age and Older In a short-term (6-week) clinical study, higher rates of suicidal ideation and behavior were reported in SIMTRIYO-treated pediatric patients with attention deficit/hyperactivity disorder (ADHD) aged 6 to 12 years than in pediatric patients treated with placebo. Risks to Patients with Serious Cardiac Disease: Avoid 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: Assess heart rate and blood pressure following increases in dosage, and periodically while on therapy. Psychiatric Adverse Reactions: If new psychotic or manic symptoms occur, consider discontinuing SIMTRIYO.

The following adverse reactions are discussed in more detail in other sections of the labeling: Suicidal Ideation and Behaviors in Pediatric Patients Aged 6 Years and Older Abuse, Misuse, and Addiction Risks to Patients with Serious Cardiac Disease Increased Blood Pressure and Heart Rate Psychiatric Adverse Reactions Hypersensitivity Reactions Long-Term Suppression of Growth in Pediatric Patients Peripheral Vasculopathy Including Raynaud's Phenomenon Serotonin Syndrome Motor and Verbal Tics, and Worsening of Tourette's Syndrome Most common adverse reactions (≥5% and greater than placebo) were: Pediatric Patients Aged: 6 to 12 Years: rash, decreased appetite 13 to 17 Years: decreased appetite, nausea, rash, headache, abdominal pain Adults: headache, decreased appetite, insomnia, nausea, dry mouth, diarrhea

Table 5 presents clinically significant drug interactions with SIMTRIYO. Table 5: Clinically Significant Drug Interactions with SIMTRIYO Monoamine Oxidase Inhibitors (MAOIs) Prevention or Management Concomitant use of SIMTRIYO with MAOIs or within 14 days after discontinuing an MAOI is contraindicated. Mechanism and Clinical Effect(s) Concomitant use of SIMTRIYO with MAOIs increases the risk of hypertensive crisis (potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure) and serotonin syndrome. Alcohol Prevention or Management Avoid consumption of alcohol at the same time as, and for at least two hours after, administration of SIMTRIYO.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F).