Vilazodone

7 DRUG INTERACTIONS CYP3A4 Inhibitors: The VIIBRYD dose should not exceed 20 mg once daily when co-administered with strong CYP3A4 inhibitors ( 2.4 , 7 ). CYP3A4 Inducers: Consider increasing VIIBRYD dosage by 2-fold, up to 80 mg once-daily over 1 to 2 weeks when used concomitantly with strong CYP3A4 inducers for greater than 14 days ( 2.4 , 7 ).

7.1 Drugs Having Clinically Important Interactions With VIIBRYD Table 4: Clinically Important Drug Interactions with VIIBRYD Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of MAOIs and serotonergic drugs including VIIBRYD increases the risk of serotonin syndrome. VIIBRYD is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Contraindications ( 4 ), Dos age and Administration ( 2.3 ) , and Warnings and Precautions ( 5.2 )].

Other Serotonergic Drugs Concomitant use of VIIBRYD with other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during VIIBRYD initiation. If serotonin syndrome occurs, consider discontinuation of VIIBRYD and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )]. Antiplatelet Agents and Anticoagulants Serotonin release by platelets plays an important role in hemostasis.

The concurrent use of an antiplatelet agent or anticoagulant with VIIBRYD may potentiate the risk of bleeding. Inform patients of the increased risk of bleeding with the concomitant use of VIIBRYD and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating, titrating, or discontinuing VIIBRYD [see Warnings and Precautions ( 5.3 )]. Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, voriconazole) The concomitant use of VIIBRYD and strong CYP3A4 inhibitors increased the exposure of vilazodone compared to the use of VIIBRYD alone [see Clinical Pharmacology ( 12.3 )].

The VIIBRYD dose should not exceed 20 mg once daily with the concomitant use of a strong CYP3A4 inhibitor [see Dosage and Administration ( 2.4 ) , Clinical Pharmacology ( 12.3 ) ] . Strong CYP3A4 Inducers (e.g., carbamazepine, phenytoin, rifampin) The concomitant use of VIIBRYD and strong CYP3A4 inducers decreased the exposure of vilazodone compared to the use of VIIBRYD alone [see Clinical Pharmacology ( 12.3 )]. Based on clinical response, consider increasing the dosage of VIIBRYD, over 1 to 2 weeks in patients taking strong CYP3A4 inducers for greater than 14 days [see Dosage and Administration ( 2.4 ) , Clinical Pharmacology ( 12.3 ) ].

Digoxin Digoxin is a narrow therapeutic index drug. Concomitant use of VIIBRYD increased digoxin concentrations [see Clinical Pharmacology ( 12.3 )] . Measure serum digoxin concentrations before initiating concomitant use of VIIBRYD. Continue monitoring and reduce digoxin dose as necessary.

7.2 Drugs Having No Clinically Important Interactions With VIIBRYD Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are substrates of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and/or P-glycoprotein (except narrow therapeutic index drugs, e.g., digoxin), when VIIBRYD is administered concomitantly [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] .

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants . Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.3 ) and Clinical Considerations] .

There are no adequate and well-controlled studies of VIIBRYD in pregnant women. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. In animal reproduction studies, oral administration of vilazodone during the period of organogenesis at doses up to 48 and 17 times the maximum recommended human dose (MRHD) in rats and rabbits, respectively, resulted in decreased fetal body weight gain and delayed skeletal ossification but no teratogenic effects were observed.

Decreased fetal body weight and delayed skeletal ossification were not observed at doses up to 10 and 4 times the MRHD in rats and rabbits, respectively [see Data] . Clinical Considerations Disease-associated m aternal and/or e mbryo/ f etal r isk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants.

Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of VIIBRYD in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.3 )] . Fetal/Neonatal adverse reactions Exposure to SSRIs and SNRIs, including VIIBRYD, in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Monitor neonates…