Gepirone

EXXUA is indicated for the treatment of major depressive disorder (MDD) in adults.

The mechanism of the antidepressant effect of EXXUA is not fully understood but is thought to be related to its modulation of serotonergic activity in the CNS through selective agonist activity at 5HT1A receptors.

Correct electrolyte abnormalities and perform electrocardiogram (ECG) prior to initiating treatment with EXXUA. Do not initiate EXXUA if QTc is > 450 msec. Perform ECGs during dosage titration and periodically during treatment. The recommended starting dose is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased to 36.3 mg once daily on Day 4. Dosage may be further titrated to 54.5 mg once daily after Day 7 and to 72.6 mg once daily after an additional week. Geriatric patients: Recommended starting dosage is 18.2 mg once daily. Dosage may be increased to 36.3 mg after 7 days. Renal Impairment (creatinine clearance < 50 mL/min): Recommended starting dosage is 18.2 mg once daily. Dosage may be increased to 36.3 mg once daily after 7 days.

EXXUA is contraindicated in patients: with known hypersensitivity to gepirone or components of EXXUA. with prolonged QTc interval > 450 msec at baseline. with congenital long QT syndrome. receiving concomitant strong CYP3A4 inhibitors. with severe hepatic impairment. 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. Starting EXXUA in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated. Known hypersensitivity to gepirone or components of EXXUA. Prolonged QTc interval > 450 msec at baseline. Congenital long QT syndrome.

BOXED WARNING WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. QT Interval Prolongation: EXXUA prolongs the QTc. Correct electrolyte abnormalities. Perform ECGs prior to initiation, during dose titration, and periodically during treatment with EXXUA. Monitor ECGs more frequently when EXXUA is used concomitantly with drugs known to prolong the QT interval, in patients who develop QTc ≥ 450 msec during treatment or are at significant risk of developing torsade de pointes. Do not escalate dosage if QTc > 450 msec. Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Adolescents and Young Adults QT Prolongation Serotonin Syndrome Activation of Mania or Hypomania Most common adverse reactions (incidence of ≥ 5% and at least twice incidence of placebo) were dizziness, nausea, insomnia, abdominal pain, and dyspepsia.

Table 3 displays clinically important drug interactions with EXXUA. Table 3 Clinically Important Drug Interactions with EXXUA CYP3A4 Inhibitors Clinical Impact Strong CYP3A4 Inhibitors Concomitant use of EXXUA with a strong CYP3A4 inhibitor increases EXXUA exposure by ~ 5-fold. Moderate CYP3A4 Inhibitors Concomitant use with a moderate CYP3A4 inhibitor increases EXXUA exposure by ~ 2.6-fold. Intervention Strong CYP3A4 Inhibitors EXXUA is contraindicated in patients taking strong CYP3A4 inhibitors. Moderate CYP3A4 Inhibitors If EXXUA is used with a moderate CYP3A4 inhibitor, reduce the dosage of EXXUA. Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of EXXUA with MAOIs increases the risk of serotonin syndrome.

Storage Store at 20°C to 25°C (68°F to 77°F), excursions are permitted between 15°C to 30°C (59°F to 86°F). Protect from high humidity and moisture.