Summary

• Paliperidone is substantially excreted unchanged by the kidney (59%), and elimination is decreased in patients with decreasing creatinine clearance (CRCL).¹
• INVEGA HAFYERA has not been systematically studied in patients with renal impairment.²
• Use of INVEGA HAFYERA is not recommended for use in patients with moderate or severe renal impairment (creatinine clearance <50 mL/min [Cockcroft-Gault Formula]).²
• For patients with mild renal impairment (creatinine clearance ≥50 mL/min to <80 mL/min), adjust dosage and stabilize the patient using INVEGA SUSTENNA before transitioning from INVEGA SUSTENNA to INVEGA HAFYERA, or from INVEGA SUSTENNA to INVEGA TRINZA to INVEGA HAFYERA.²
  • Refer to the Prescribing Information of INVEGA SUSTENNA or INVEGA TRINZA for the recommended dosages in patients with mild renal impairment.
• A population pharmacokinetic (popPK) model-based simulation of paliperidone pharmacokinetics (PK) after the administration of INVEGA HAFYERA using data from the phase 3, double-blind (DB), noninferiority study reported that exposure to paliperidone was similar for INVEGA HAFYERA 1560 mg (1000 mg equivalent [eq.]) in patients with normal renal function and INVEGA HAFYERA 1092 mg (700 mg eq.) in patients with mild renal impairment (RI).³

CLINICAL DATA

T’jollyn et al (2024)³ reported a popPK model-based simulation that characterized the PK of INVEGA HAFYERA to provide guidance on different dosing scenarios (initiation, maintenance, and missed doses) and dosing in special populations, including patients with RI. Data was sourced from the phase 3, DB, noninferiority study⁴ that evaluated the efficacy and safety of INVEGA HAFYERA for the treatment of adult patients with schizophrenia who were previously stabilized on INVEGA SUSTENNA or INVEGA TRINZA.

Study Design/Methods

• The popPK model utilized structural covariates CRCL, body mass index, and sex to evaluate the influence on paliperidone PK after INVEGA HAFYERA administration in special populations. For the definition of CRCL covariate used in the analysis, see Table: Covariate - Creatinine Clearance.
• Simulations were performed using the popPK model to determine the appropriate dosing of INVEGA HAFYERA in patients with mild RI.
• The dose reduction of INVEGA HAFYERA for patients with mild RI was estimated by comparing the dosing with INVEGA HAFYERA 1560 mg (1000 mg eq.) in patients with normal renal function vs with INVEGA HAFYERA 1092 mg (700 mg eq.) in patients with mild RI.

Results

• The PK dataset comprised 15,932 samples from 700 patients from the DB study (male, 68.4%, median [range] age, 40.0 [18-69] years; median [range] CRCL, 121 [60-262] mL/min; INVEGA TRINZA, 5148 [32%] samples from 223 patients; INVEGA HAFYERA, 10,784 [68%] samples from 477 patients).
• The median values of maximum serum concentration (C_max) and trough concentration (C_trough) of paliperidone increased by 19.1% and 19.5%, respectively, in patients with mild RI (50-80 mL/min) compared to patients with normal renal function when both groups were receiving maintenance doses of INVEGA HAFYERA 1560 mg (1000 mg eq.).
• The median C_max and C_trough of paliperidone decreased by 15.4% and 17.7%, respectively, in patients with mild RI after receiving a reduced dose of INVEGA HAFYERA 1092 mg (700 mg eq.) compared to patients with normal renal function who received INVEGA HAFYERA 1560 mg (1000 mg eq.).
• Irrespective of the CRCL cutoffs used, the paliperidone exposure in patients with mild RI who received INVEGA HAFYERA 1092 mg (700 mg eq.) was similar to patients with normal renal function who received INVEGA HAFYERA 1560 mg (1000 mg eq.).  

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT Drug File(and/or other resources, including internal/external databases) pertaining to this topic was conducted on 10 June 2024.