Gepirone

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 [see Clinical Pharmacology (12.3) ] . Moderate CYP3A4 Inhibitors Concomitant use with a moderate CYP3A4 inhibitor increases EXXUA exposure by ~ 2.6-fold [see Clinical Pharmacology (12.3) ] . Intervention Strong CYP3A4 Inhibitors EXXUA is contraindicated in patients taking strong CYP3A4 inhibitors [see Dosage and Administration (2.7) , Contraindications (4) , and Warnings and Precautions (5.2) ] .

Moderate CYP3A4 Inhibitors If EXXUA is used with a moderate CYP3A4 inhibitor, reduce the dosage of EXXUA [see Dosage and Administration (2.7) and Warnings and Precautions (5.2) ]. Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of EXXUA with MAOIs increases the risk of serotonin syndrome. Intervention EXXUA is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue or in patients who have taken MAOIs within the preceding 14 days. Allow at least 14 days after stopping EXXUA before starting an MAOI [see Dosage and Administration (2.8) , Contraindications (4) , and Warnings and Precautions (5.3) ].

Drugs that Prolong the QTc Interval Clinical Impact Concomitant use of drugs that prolong the QTc interval may add to the QTc prolonging effects of EXXUA and increase the risk of cardiac arrhythmias. Intervention Monitor patients with ECGs more frequently if EXXUA is administered with other drugs known to prolong QT interval [see Warnings and Precautions (5.2) ] . CYP3A4 Inducers Clinical Impact Concomitant use of EXXUA with a strong CYP3A4 inducer reduces EXXUA exposure by 20- to 29-fold [see Clinical Pharmacology (12.3) ] . Intervention Avoid concomitant use of EXXUA in patients taking strong CYP3A4 inducers.

Other Serotonergic Drugs Clinical Impact Concomitant use of EXXUA and serotonergic drugs increases the risk of serotonin syndrome. Intervention Monitor for symptoms of serotonin syndrome when EXXUA is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinuation of EXXUA and/or concomitant serotonergic drug [see Warnings and Precautions (5.3) ] . Strong CYP3A4 inducers: Reduces EXXUA exposure. Avoid concomitant use ( 7 ).

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).

There are insufficient clinical data on gepirone use during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are clinical considerations regarding neonates exposed to serotonergic antidepressants during the third trimester of pregnancy (see Clinical Considerations and Data). There are risks associated with untreated depression during pregnancy (see Clinical Considerations). Consider if the risks outweigh the benefits of treatment with gepirone during pregnancy. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S.

general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryofetal Risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy.

Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Fetal/Neonatal Adverse Reactions Neonates exposed to other…