What is the recommended dose of Gemtessa (elagolix) for a patient with impaired renal function?

Gemtessa (Elagolix) Dosing in Renal Impairment

No dose adjustment is required for Gemtessa (elagolix) in patients with any degree of renal impairment, including end-stage renal disease requiring dialysis. 1

Evidence-Based Rationale

Pharmacokinetic Profile

• Elagolix undergoes primarily hepatic metabolism via CYP3A (major pathway), with minimal renal elimination—less than 3% of the dose is excreted unchanged in urine 1
• The drug's clearance mechanism is fundamentally different from renally-eliminated medications, making renal function irrelevant to dosing decisions 1

Clinical Pharmacokinetic Studies

• Direct pharmacokinetic studies in women with renal impairment demonstrated that elagolix exposures (Cmax and AUC) are not altered by renal dysfunction 1, 2
• Mean drug exposures remain similar across all categories: normal renal function, moderate-to-severe renal impairment, and end-stage renal disease (including patients on dialysis) 1, 2
• This finding was confirmed in dedicated phase 1 studies specifically designed to assess safety and pharmacokinetics in women with varying degrees of renal impairment 2

Standard Dosing Across All Renal Function Levels

Use the regular approved doses regardless of creatinine clearance:

• 150 mg once daily for the lower-dose regimen 1
• 200 mg twice daily for the higher-dose regimen 1

No Adjustments Needed For:

• Mild renal impairment (CrCl 60-89 mL/min) 1
• Moderate renal impairment (CrCl 30-59 mL/min) 1
• Severe renal impairment (CrCl 15-29 mL/min) 1
• End-stage renal disease (CrCl <15 mL/min) 1
• Patients requiring hemodialysis 1, 2

Critical Distinction: Hepatic vs. Renal Impairment

This is a common pitfall—do not confuse renal and hepatic dosing requirements for elagolix:

• While renal impairment requires no adjustment, hepatic impairment dramatically increases elagolix exposure 1, 2
• Moderate hepatic impairment increases exposure approximately 3-fold 1, 2
• Severe hepatic impairment increases exposure approximately 7-fold 1, 2
• Always assess liver function separately, as dose modifications or contraindications apply in hepatic dysfunction 1

Safety Profile in Renal Impairment

• Adverse event incidence remained low in renal impairment studies, with only mild nausea and headache reported as main events 2
• The safety profile in patients with renal dysfunction mirrors that of patients with normal renal function 2