SUMMARY

• For patients with moderate or severe hepatic impairment (HI) (Child-Pugh class B or C), the recommended dosage of CAPLYTA is 21 mg once daily.¹
• The recommended dosage in patients with mild HI (Child-Pugh class A) is the same as those with normal hepatic function.¹
• A study was performed to evaluate the pharmacokinetic (PK) profile, safety, and tolerability of a single dose of lumateperone 14 mg administered orally to patients with mild (n=8), moderate (n=8), and severe (n=8) HI, as well as matched healthy subjects (n=8).² 
  • After oral administration of the single dose, mean lumateperone maximum plasma concentration (C_max) and mean area under the curve (AUC_0-t) in patients with hepatic impairment was higher than in healthy subjects. 
  • The mean half-life (t_1/2) of lumateperone increased with severity of HI, from 2.05 hours in healthy subjects to 4.15 hours in patients with severe HI.

PRODUCT LABELING

Dosage Recommendations for Patients with Hepatic Impairment

For patients with moderate HI (Child-Pugh class B) or severe HI (Child-Pugh class C), the recommended CAPLYTA dosage is 21 mg once daily. The recommended CAPLYTA dosage in patients with mild HI is the same as those with normal hepatic function.¹

Hepatic Impairment

Patients with moderate HI (Child-Pugh class B) and severe HI (Child-Pugh class C) generally had higher exposure to lumateperone than patients with normal hepatic function; therefore, the recommended CAPLYTA dosage in patients with moderate or severe HI is lower than those with normal hepatic function.

The recommended dosage in patients with mild HI (Child-Pugh class A) is the same as those with normal hepatic function.¹

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 uridine 5’-diphospho-glucuronosyltransferases (UDP-glucuronosyltransferase, UGT) 1A1, 1A4, and 2B15, aldoketoreductase (AKR)1C1, 1B10, and 1C4, and cytochrome P450 (CYP) 3A4, 2C8, and 1A2, are involved in the metabolism of lumateperone.¹

CLINICAL DATA

A study was performed to evaluate the PK profile, safety, and tolerability of a single dose of lumateperone 14 mg administered orally to patients with mild (n=8), moderate (n=8), and severe (n=8) HI, as well as matched healthy subjects (n=8).² 

• After oral administration of the single dose, mean lumateperone C_max in patients with HI was higher than in healthy subjects.
• Median time to maximum plasma concentration (T_max) was similar across all groups, with a range of 1.33 to 2.00 hours.
• Mean AUC_0-t was also higher in patients with HI than in healthy subjects.
• The mean t_1/2 of lumateperone increased with severity of HI, from 2.05 hours in healthy subjects to 4.15 hours in patients with severe HI.
• The results of the study showed a moderate to high between-subject variation in systemic exposure, ranging from 31.8% to 87.2% across all groups. Except for t_1/2, all PK parameters reached maximum difference from the normal group in patients with moderate HI, though variability was high and ranges for each parameter overlapped.
• In general, systemic exposures (C_max and AUC) to parent and metabolites IC200161 and IC200131 were higher in all HI groups. The difference was most pronounced in patients with moderate impairment.
• Overall, systemic exposure to lumateperone and certain metabolites increases with moderate-to-severe HI. The clinical significance of these changes is difficult to assess, given the variability in the data. However, a reduced dose should be considered in patients with moderate-to-severe HI.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 29 September 2025.