SUMMARY

• Advise patients to inform their health care providers of any changes to their current prescription or over-the-counter drugs because there is a potential for clinically significant interactions.¹
• Avoid concomitant use of CAPLYTA with cytochrome P450 (CYP) 3A4 inducers.¹
• The recommended dosage for patients receiving strong CYP3A4 inhibitors is CAPLYTA 10.5 mg once daily.¹
• The recommended dosage for patients receiving moderate CYP3A4 inhibitors is CAPLYTA 21 mg once daily.¹
• In vitro studies show that multiple enzymes, including but not limited to uridine 5’-diphospho-glucuronosyltransferases (UDP-glucuronosyltransferase, UGT) 1A1, 1A4, and 2B15, aldoketoreductase (AKR)1C1, 1B10, and 1C4, and CYP3A4, 2C8, and 1A2, are involved in the metabolism of lumateperone.¹

PRODUCT LABELING

Dosage Recommendations for Concomitant Use with Moderate or Strong CYP3A4 Inhibitors

The recommended CAPLYTA dosage in patients who receive¹:

• Strong CYP3A4 inhibitors is CAPLYTA 10.5 mg once daily.
• Moderate CYP3A4 inhibitors is CAPLYTA 21 mg once daily.

Clinically Important Drug Interactions with CAPLYTA

Metabolism

Lumateperone is extensively metabolized with more than twenty metabolites identified in vivo. After a single ¹⁴C-labeled oral dose, lumateperone and glucuronidated metabolites represent about 2.8% and 51% of the total plasma radioactivity, respectively. In vitro studies show that multiple enzymes, including but not limited to UGT1A1, 1A4, and 2B15, AKR1C1, 1B10, and 1C4, and CYP3A4, 2C8, and 1A2, are involved in the metabolism of lumateperone.¹

Drug Interaction Studies

Clinical Studies

Strong CYP3A4 Inhibitors: Itraconazole (strong CYP3A4 inhibitor) increased geometric mean (90% confidence interval) of lumateperone area under the concentration vs time curve (AUC_t) by 3.8-fold (3.2, 4.5) and lumateperone peak plasma concentration (C_max) by 3.2-fold (2.8, 3.7).¹

Moderate CYP3A4 Inhibitors: Diltiazem (moderate CYP3A4 inhibitor) increased geometric mean (90% confidence interval) of lumateperone AUC_t by 2.3-fold (1.6, 3.3) and lumateperone C_max by 1.9-fold (1.3, 2.6).¹

Strong CYP3A4 Inducers: Rifampin (strong CYP3A4 inducer) decreased geometric mean (90% confidence interval) of lumateperone AUC_t by 98% (96%, 99%) and lumateperone C_max by 92% (87%, 95%).¹

UGT inhibitors: There were no clinically significant drug interactions with the UGT inhibitors probenecid and valproic acid.¹

CYP3A4 substrates: No clinically significant differences in the pharmacokinetics of midazolam (CYP3A4 substrate) or its metabolite 1-hydroxymidazolam were observed when used concomitantly with single or multiple doses of lumateperone in patients with schizophrenia.¹

In Vitro Studies

Lumateperone showed little to no inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5. It showed no induction of CYP1A2, CYP2B6, or CYP3A4.¹

Lumateperone did not appear to be a P-glycoprotein or breast cancer resistance protein substrate. It showed little to no inhibition of OCT2, OAT1, OAT3, OATP1B3, or OATP1B1.¹

Concomitant Drugs

Advise patients to inform their health care providers of any changes to their current prescription or over-the-counter drugs because there is a potential for clinically significant interactions.¹

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 September 2025.