EXXUA

2 DOSAGE AND ADMINISTRATION Correct electrolyte abnormalities and perform electrocardiogram (ECG) prior to initiating treatment with EXXUA. 1 ). 1 ). 3 ). 3 mg once daily on Day 4. 3 ). 2 mg once daily. 4 ). 2 mg once daily. 6 ). 7 ). 7 ). 1 Important Recommendations Prior to Initiating and During Treatment with EXXUA Electrocardiogram and Electrolyte Monitoring Correct electrolyte abnormalities prior to initiating EXXUA.

2) ]. Perform an electrocardiogram (ECG) prior to initiating EXXUA, during dosage titration, and periodically during treatment. Do not initiate EXXUA if QTc is > 450 msec at baseline. 2) and Drug Interactions (7) ]. 2) ]. 3) ] . 3) ] . Swallow tablets whole.

Do not split, crush, or chew EXXUA. 2 mg once daily. 6 mg orally once daily after an additional week. 6 mg once daily. 2 mg orally once daily. 3) ]. 2 mg orally once daily. 3) ]. 3) ] . 2 mg once daily. 3 ) ] . 3) ] . The recommended dosage in patients with mild (Child-Pugh A) hepatic impairment is the same as patients with normal hepatic function.

7 Dosage Modifications for Concomitant Use with CYP3A4 Inhibitors Reduce the EXXUA dose by 50% when used concomitantly with a moderate CYP3A4 inhibitor [see Drug Interactions (7) ] . EXXUA is contraindicated in patients receiving strong CYP3A4 inhibitors [see Contraindications (4) and Drug Interactions (7) ] .

8 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant At least 14 days must elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with EXXUA. Conversely, at least 14 days must be allowed after stopping EXXUA before starting an MAOI antidepressant [see Contraindications (4) and Drug Interactions (7) ] .

1 ). gov/medwatch . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

During premarketing assessment, multiple doses of EXXUA were administered to 1,976 adult patients with major depressive disorder (MDD) in controlled phase 2 and 3 clinical studies, including 1,639 patients in placebo-controlled phase 2 and 3 trials in MDD, with 237 patients exposed for over six months.

The population treated with EXXUA in the pooled placebo-controlled studies ranged from 15 to 78 years of age, was 34% male and 66% female, and was 80% Caucasian, 11% Black, and 9% other race. 6 mg (n=226) or placebo (n=230) was administered to adult patients with MDD during an 8-week double-blind treatment period [see Clinical Studies (14) ] .

Study 1 had a median age of 39 years and were 61% female, 73% Caucasian, 9% Black, 2% Asian, and 16% Other (Hispanic or Native American). Study 2 had a median age of 39 years and were 69% female, 65% Caucasian, 23% Black, 1% Asian, and 11% Hispanic.

In Study 1 and Study 2, 7% (15/226) of patients treated with EXXUA and 3% (6/230) of patients receiving placebo discontinued treatment due to an adverse reaction. The most common reactions leading to discontinuation for patients taking EXXUA were dizziness and nausea.

The most common adverse reactions (≥ 5% and twice the incidence of placebo) in EXXUA-treated patients were dizziness, nausea, insomnia, abdominal pain, and dyspepsia. Table 2 presents the adverse reactions that occurred at an incidence of ≥ 2% of patients treated with EXXUA and at a higher incidence than in the placebo-treated patients.

5 WARNINGS AND PRECAUTIONS 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.

2 , 7 ).

Serotonin Syndrome:

Increased risk when co-administered with other serotonergic agents. 3 ). 4 ). 1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients, and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients aged 24 years and younger was greater than in placebo-treated patients.

There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD.

The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1 . Table 1 Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric EXXUA is not approved for use in pediatric patients.

, beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that the use of antidepressants can delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.

1) ] . 2) ]. 2) ]. 2) and Drug Interactions (7) ]. 7) ]. 3) and Drug Interactions (7) ] . 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 ( 4 ).

Prolonged QTc interval > 450 msec at baseline ( 4 ). Congenital long QT syndrome ( 4 ). Concomitant use of strong CYP3A4 inhibitors ( 4 ). Severe hepatic impairment ( 4 ). Use with an MAOI or within 14 days of stopping treatment with EXXUA.

Do not use EXXUA within 14 days of discontinuing an MAOI ( 4 ).