OPSUMIT - Renal Impairment and Dialysis

SUMMARY

• In the phase 3 SERAPHIN study, patients with severe renal impairment (estimated creatinine clearance [CrCl], <30 mL/min) were excluded.¹ No subgroup analysis was performed for patients with other degrees of renal impairment at baseline.²
• A study investigated the pharmacokinetics (PK) of macitentan in subjects with severe renal impairment (n=8) compared with that in healthy subjects with normal renal function (n=8). The differences were not considered clinically relevant and therefore, no dosage adjustment is considered necessary in patients with renal impairment.³
• A search of the scientific literature retrieved four case reports (1 article and 3 congress abstracts) describing the administration of macitentan in patients with comorbid renal disease.^4-7
• There has been no clinical research designed to investigate the efficacy and safety of OPSUMIT in patients with pulmonary arterial hypertension (PAH) undergoing renal dialysis.
• Overall, there is no substantive clinical experience with the use of OPSUMIT in patients with PAH undergoing renal dialysis. Therefore, no guidance can be given regarding the efficacy and safety of OPSUMIT in these patient populations.

CLINICAL DATA

Renal Impairment

Information From the SERAPHIN Study in Patients With PAH

In the OPSUMIT pivotal trial for PAH (SERAPHIN), subjects with an estimated CrCl,
<30 mL/min were excluded; however, otherwise renally impaired subjects were included in this study.¹ No subgroup analysis of safety/efficacy by severity of renal impairment was conducted.²

Information From Other Studies

The PK, tolerability, and safety of macitentan have been investigated in patients (aged 1860 years) with severe renal function impairment (SRFI) in the phase 1 study AC055112.³ In this prospective, single-center, parallel group, open-label, single-dose study, patients with SRFI (CrCl, 15–29 mL/min; n=8) and healthy subjects with normal renal function (CrCl, >70 mL/min in subjects ≥50 years of age; >80 mL/min in subjects <50 years of age; n=8) were administered a single oral dose of macitentan and assessed up to day 14 post-dose. Plasma concentration-time profiles for macitentan and ACT-132577, the active metabolite, were increased by 1.3- and 1.6-fold, respectively, in patients with SRFI compared to healthy subjects. Exposure to the inactive metabolite ACT-373898 was 7.3-fold higher in patients with SRFI compared to healthy subjects. However, as ACT-373898 comprised approximately 3% of the total exposure in healthy subjects, this increase was not considered clinically relevant. Macitentan was considered well tolerated in both groups.³

Four case reports (1 article and 3 congress abstracts) describe the administration of macitentan in patients with PAH and comorbid renal impairment.^4-7

Renal Dialysis

There has been no clinical research designed to investigate the efficacy and safety of macitentan in patients with PAH undergoing renal dialysis. There is no substantive clinical experience with the use of OPSUMIT in patients with PAH undergoing hemodialysis or with severe renal impairment. Therefore, no guidance can be given regarding the efficacy and safety of OPSUMIT in these patient populations.

LITERATURE SEARCH 

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 05 December 2025.