Gepirone

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.

• EXXUA is indicated for the treatment of major depressive disorder (MDD) in adults. EXXUA is indicated for the treatment of major depressive disorder (MDD) in adults ( 1 ).ICD-10: F32.9

• EXXUA is contraindicated in patients: with known hypersensitivity to gepirone or components of EXXUA [see Adverse Reactions (6.1) ] . with prolonged QTc interval > 450 msec at baseline [see Warnings and Precautions (5.2) ].contraindicated

Correct electrolyte abnormalities and perform electrocardiogram (ECG) prior to initiating treatment with EXXUA. Do not initiate EXXUA if QTc is > 450 msec ( 2.1 ). Perform ECGs during dosage titration and periodically during treatment ( 2.1 ). The recommended starting dose is 18.2 mg administered orally once daily with food at approximately the same time each day ( 2.2 , 2.3 ). 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 ( 2.3 ). Geriatric patients: Recommended starting dosage is 18.2 mg once daily. Dosage may be increased to 36.3 mg after 7 days ( 2.4 ). 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 ( 2.5 , 8.6 ). Moderate Hepatic Impairment (Child-Pugh B): Dosage may be increased to 36.3 mg once daily after 7 days ( 2.6 , 8.7 ). Adjust EXXUA dose by 50% when a moderate CYP3A4 inhibitor is administered ( 2.7 ). 2.1 Important Recommendations Prior to Initiating and During Treatment with EXXUA Electrocardiogram and Electrolyte Monitoring Correct electrolyte abnormalities prior to initiating EXXUA. In patients with electrolyte abnormalities, or who are receiving diuretics or glucocorticoids, or who have a history of hypokalemia or hypomagnesemia, also monitor electrolytes during dose titration and periodically during treatment with EXXUA [see Warnings and Precautions (5.2) ].

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 ( 2.1 , 5.2 , 7 ). Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents. If serotonin syndrome occurs, discontinue EXXUA and initiate supportive measures ( 5.3 ). Activation of Mania/Hypomania: Screen patients for bipolar disorder ( 5.4 ). 5.1 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 following adverse reactions are discussed in greater detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings and Precautions (5.1) ] QT Prolongation [see Warnings and Precautions (5.2) ] Serotonin Syndrome [see Warnings and Precautions (5.3) ] Activation of Mania or Hypomania [see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence of ≥ 5% and at least twice incidence of placebo) were dizziness, nausea, insomnia, abdominal pain, and dyspepsia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Aytu Therapeutics at 1-855-298-8246 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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.

Pregnancy: Third trimester use may increase the risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, irritability) in the neonate ( 8.1 ). 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including EXXUA, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/. Risk Summary Based on animal reproduction studies, gepirone has been shown to have adverse effects on embryo/fetal and postnatal development. In rats, increased mortality during the first 4 days after birth and persistent reduction in body weight through lactation and weaning were observed at all doses and increased still births were seen with a no observed adverse effect level (NOAEL) at 3 times the maximum recommended human dose (MRHD) on a mg/m 2 basis. In embryofetal development studies in rats and rabbits, decreased embryofetal growth, body weights and lengths, with accompanying skeletal variations were seen with a NOAEL at 9 and 12 times the MRHD on a mg/m 2 basis, respectively (see Data).

Metabolism

The pharmacokinetics of EXXUA are linear and dose proportional from 18.2 mg to 72.6 mg. Steady-state plasma concentration are typically achieved within two to four days of daily dosing.

In clinical studies, cases of acute ingestions up to 454 mg (6.25 times the maximum recommended dose) of EXXUA alone or in combination with other drugs, were reported. Signs and symptoms reported with overdose of EXXUA at doses up to 454 mg included vomiting and transient incomplete bundle branch block; an unknown dose of EXXUA produced altered level of consciousness and a 60-second convulsion. No specific antidotes for EXXUA are known. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

• Sep 22, 2023NDANDA021164Fabre Kramer

The 1 most recently updated of 1 ClinicalTrials.gov registrations naming Gepirone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Gepirone vs Placebo in Treatment of Cocaine Dependence - 3
  Completed · Phase 2 · Interventional · 41 enrolled · University of Pennsylvania
  NCT00000189updated 2015-05-28

Frequently asked questions

How does Gepirone work?

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.

What is Gepirone used for?

According to FDA labeling, Gepirone carries indications including: EXXUA is indicated for the treatment of major depressive disorder (MDD) in adults. EXXUA is indicated for the treatment of major depressive disorder (MDD) in adults ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Gepirone?

Gepirone is classified as Other antidepressants, Serotonin Agonists, Serotonin Receptor Interactions, Increased Serotonin Activity.

What are the brand names for Gepirone?

Gepirone is marketed under brand names including Exxua.

What are the contraindications for Gepirone?

Gepirone labeling lists contraindications including: EXXUA is contraindicated in patients: with known hypersensitivity to gepirone or components of EXXUA [see Adverse Reactions (6.1) ] . with prolonged QTc interval > 450 msec at baseline [see Warnings and Precautions (5.2) ].. Always consult the full prescribing information and a clinician.