Exxua From Fabre-Kramer Pharmaceuticals

The FDA has approved Gepirone (Exxua) oral extended-release tablets from Fabre-Kramer Pharmaceuticals for the treatment of major depressive disorder (MDD) in adults.¹ Millions of individuals worldwide are affected by MDD, with more than 80 million Americans experiencing symptoms of depression.²

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PHARMACOLOGY AND PHARMACOKINETICS

Gepirone is a selective 5HT1a receptor agonist that displays dose-proportional and linear pharmacokinetics. It reaches maximal plasma concentrations within 6 hours of administration and has a mean terminal half-life of approximately 5 hours.^1,2

DOSAGE AND ADMINISTRATION

Prior to beginning treatment with gepirone, a patient should have any electrolyte abnormalities corrected and an electrocardiogram (ECG) obtained. Treatment should not be initiated if the heart rate–corrected QT interval (QTc) is greater than 450 milliseconds. The recommended starting dose is 18.2 mg orally once daily, taken with food at approximately the same time each day. If tolerated and clinically appropriate, the dose may be increased to 36.3 mg once daily on day 4, 54.5 mg once daily after day 7, and 72.6 mg once daily after day 14. The recommended starting dose for geriatric patients and patients with renal impairment (creatinine clearance < 50mL/min) or moderate hepatic impairment (Child-Pugh class B) is 18.2 mg once daily, which may be increased to 36.3 mg once daily after 7 days. ECGs should be obtained during dose titration and periodically thereafter. The dose should be reduced by 50% when coadministered with a moderate cytochrome P450 (CYP) 3A4 inhibitor.¹

CLINICAL TRIALS

The efficacy of gepirone for the treatment of MDD in adults was evaluated in 2 double-blind, flexible-dose, placebo-controlled, randomized studies in patients who met the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for MDD. The primary efficacy measure in both studies was the change from baseline in the Hamilton Depression Rating Scale total score at week 8. Both studies demonstrated a statistically significant improvement on the primary end point in the patients using gepirone compared with those using the placebo.¹

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Gepirone carries a boxed warning stating that short-term studies demonstrated an increased risk of suicidal behaviors and thoughts in pediatric and young adult patients who were using antidepressants. All patients using antidepressant medications should be closely monitored for clinical worsening and emergence of suicidal behaviors and thoughts. Gepirone is not approved for use in pediatric patients.

Gepirone is contraindicated in patients with a known hypersensitivity to the medication or any of its components, prolonged baseline QTc interval greater than 450 milliseconds, congenital long QT syndrome, concomitant use of strong CYP3A4 inhibitors, severe hepatic impairment, or when used concomitantly with or within 14 days of discontinuing a monoamine oxidase inhibitor (MAOI). Treatment with a MAOI is contraindicated within 14 days of discontinuing gepirone.

Because gepirone prolongs the QTc, electrolyte abnormalities should be
corrected and ECGs performed before treatment initiation, during dose
titration, and periodically thereafter. ECGs should be monitored more
frequently when gepirone is used concomitantly with drugs known to
prolong the QT interval, in patients who develop QTc greater than or equal to 450 milliseconds during treatment, or who are at significant risk of developing torsade de pointes. The dose should not be increased if the QTc is greater than 450 milliseconds.
There is a greater risk for serotonin syndrome when gepirone is coadministered with other serotonergic agents. If this occurs, gepirone should be discontinued and supportive measures initiated. Because antidepressant treatment can precipitate a hypomanic, manic, or mixed manic episode, patients should be screened for bipolar disorder before beginning treatment.
Concomitant use of strong CYP3A4 inducers reduces gepirone exposure and should be avoided. Use of gepirone in the third trimester of pregnancy may increase the risk for persistent pulmonary
hypertension and symptoms of poor adaptation in the neonate.
The most common adverse reactions are abdominal pain, dizziness, dyspepsia, insomnia, and nausea.¹

About the Author

Monica Holmberg, PharmD, BCPS, is a pharmacist in Phoenix, Arizona, and a Pharmacy Times® contributor.

References

1. Exxua. Prescribing information. Fabre-Kramer Pharmaceuticals; 2023. Accessed October 5, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021164s000lbl.pdf
2. Fabre-Kramer Pharmaceuticals announces FDA approval of EXXUA, the first and only oral selective 5HT1a receptor agonist for the treatment of major depressive disorder in adults. News release. Fabre-Kramer Pharmaceuticals Inc. September 28, 2023. Accessed October 5, 2023. https://fabrekramer.com/fabre-kramer-pharmaceuticals-announcesfda-approval-of-exxua-the-first-and-only-oralselective-5ht1a-receptor-agonist-for-the-treatment-of-major-depressive-disorder-in-adults/