SIMTRIYO Extended-release capsule Ref.[116784] Active ingredients: Centanafadine

2.1 Testing and Screening Recommendations Prior to and During Treatment with SIMTRIYO

Prior to treating patients with SIMTRIYO, assess:

• The risk of abuse, misuse, and addiction [see Warnings and Precautions (5.2)].
• For the presence of cardiac disease (e.g., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.3)].
• Heart rate and blood pressure [see Warnings and Precautions (5.4)].
• The risk factors for developing a manic episode (e.g., history of depressive symptoms or a family history of suicide, bipolar disorder, or depression) [see Warnings and Precautions (5.5)].
• For a family history of tics or Tourette' syndrome and clinically evaluate patients for motor or verbal tics or Tourette's syndrome [see Warnings and Precautions (5.10)].

2.2 Recommended Dosage

Pediatric Patients 6 Years of Age and Older Weighing at Least 20 kg

In pediatric patients 6 to 12 years of age weighing at least 20 kg, the recommended SIMTRIYO dosage is based on weight and is provided in Table 1.

Table 1. Recommended Oral Once Daily Dosage of SIMTRIYO in Pediatric Patients 6 to 12 years of Age by Body Weight:

In pediatric patients 13 to 17 years of age weighing at least 20 kg, the recommended SIMTRIYO dosage is 280 mg orally once daily.

The effectiveness of SIMTRIYO 140 mg once daily in patients aged 13 to 17 years and the weight-based equivalent dosage in patients aged 6 to 12 years was not established [see Clinical Studies (14)]. SIMTRIYO 210 mg once daily and weight-based equivalent dosages have not been studied in pediatric patients aged 6 to 17 years and are not recommended.

Adults

In adults, the recommended starting dosage of SIMTRIYO is 210 mg orally once daily. The dosage may be increased to the maximum recommended dosage of 280 mg once daily based on clinical response and tolerability.

2.3 Administration Instructions

Administer SIMTRIYO orally, in the morning, with or without food, at approximately the same time each day [see Clinical Pharmacology (12.3)]. Do not cut, crush, or chew the capsules.

Take SIMTRIYO capsules whole or open the capsule and sprinkle the entire contents over one tablespoon (15 mL) of applesauce or yogurt or in one tablespoon (15 mL) of orange juice. Consume immediately followed by water. Do not chew the granules. Do not save for later use.

2.4 Starting SIMTRIYO After Use of a Monoamine Oxidase Inhibitor

Must wait at least 14 days after stopping a monoamine oxidase inhibitor (MAOI) before starting SIMTRIYO [see Contraindications (4), Warnings and Precautions (5.9), and Drug Interactions (7)].

2.5 Missed Doses

If a dose of SIMTRIYO is missed, administer the missed dose as soon as remembered but no later than 4 hours after the normal dosing time. Patients should not take more than one dose of SIMTRIYO in the same day.

Human Experience

There is limited clinical trial experience regarding SIMTRIYO overdosage in humans. During a premarketing clinical study with an immediate-release centanafadine formulation, vomiting, tachypnea, tachycardia, and elevations of blood pressure were observed at concentrations higher than the recommended dosage of SIMTRIYO.

Posterior reversible encephalopathy syndrome (PRES) symptoms including headache, altered mental status, hypertension, seizures, and visual disturbances including blindness have occurred in the setting of a CNS stimulant overdose. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Diagnosis of PRES should be confirmed by radiological procedure (e.g., MRI).

Treatment and Management

If an overdose of SIMTRIYO occurs, administer supportive care, symptomatic treatment and clinical monitoring as appropriate. Consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

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) [see USP Controlled Room Temperature].