Given the primary CNS effects of Latuda, caution should be used when it is taken in combination with other centrally acting drugs and alcohol.
Potential for Other Drugs to Affect Latuda
Latuda is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP4A11, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 enzymes. This suggests that an interaction of Latuda with drugs that are inhibitors or inducers of these enzymes is unlikely.
Latuda is predominantly metabolized by CYP3A4; interaction of Latuda with strong and moderate inhibitors or inducers of this enzyme has been observed (Table: Summary of Effect of Coadministered Drugs on Exposure to Latuda in Healthy Subjects or Patients with Schizophrenia). Latuda should not be used in combination with strong inhibitors or inducers of this enzyme [see Contraindications (4)].
Table: Summary of Effect of Coadministered Drugs on Exposure to Latuda in Healthy Subjects or Patients with Schizophrenia
|Coadministered drug||Dose schedule||Effect on Latuda pharmacokinetics||Recommendation|
(strong CYP3A4 inhibitor)
|400 mg/day for 5 days||10 mg single dose||6.9-times Latuda alone||9-times Latuda alone||Should not be coadministered with Latuda|
(moderate CYP3A4 inhibitor)
|240 mg/ day for 5 days||20 mg single dose||2.1-times Latuda alone||2.2- times Latuda alone||Latuda dose should not exceed 40 mg/day if coadministered|
(strong CYP3A4 inducer)
|600 mg/day for 8 days||40 mg single dose||1 /7th of Latuda alone||1/5th of Latuda alone||Should not be coadministered with Latuda|
|Lithium||600 mg BID for 8 days||120 mg/day for 8 days||0.9-times Latuda alone||1.1-times Latuda alone||No Latuda dose adjustment required.|
Potential for Latuda to Affect Other Drugs
Digoxin (P-gp substrate):
Coadministration of Latuda (120 mg/day) at steady state with a single dose of digoxin (0.25 mg) increased Cmax and AUC(0-24) for digoxin by approximately 9% and 13%, respectively relative to digoxin alone. Digoxin dose adjustment is not required when coadministered with Latuda.
Midazolam (CYP3A4 substrate):
Coadministration of Latuda (120 mg/day) at steady state with a single dose of 5 mg midazolam increased midazolam Cmax and AUC(0-24) by approximately 21% and 44%, respectively relative to midazolam alone. Midazolam dose adjustment is not required when coadministered with Latuda.
Oral Contraceptive (estrogen/progesterone):
Coadministration of Latuda (40 mg/day) at steady state with an oral contraceptive (OC) containing ethinyl estradiol and norelgestimate resulted in equivalent AUC(0-24) and Cmax of ethinyl estradiol and norelgestromin relative to OC administration alone. Also, sex hormone binding globulin levels were not meaningfully affected by coadministration of Latuda and OC. Dose adjustment of OC dose is not required when coadministered with Latuda.
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