Relugolix Use in Adult Females with Uterine Fibroids and Impaired Liver or Kidney Function
Relugolix can be used safely in women with mild to moderate hepatic impairment (Child-Pugh A or B) and mild to severe renal impairment (creatinine clearance 15-89 mL/min) without dose adjustment, but it has not been evaluated in severe hepatic impairment (Child-Pugh C) or end-stage renal disease requiring hemodialysis and should be avoided in these populations. 1
Renal Impairment Guidelines
No dose adjustment is required for renal impairment up to severe disease:
Mild to severe renal impairment (CLcr 15-89 mL/min): No clinically meaningful differences in relugolix pharmacokinetics were observed, and standard dosing (360 mg loading dose followed by 120 mg daily) can be used without modification 1
End-stage renal disease with or without hemodialysis: The effect on relugolix pharmacokinetics has not been evaluated, and use should be avoided in this population due to lack of safety data 1
Hepatic Impairment Guidelines
Relugolix can be used in compensated liver disease but must be avoided in decompensated cirrhosis:
Mild to moderate hepatic impairment (Child-Pugh A or B): No clinically meaningful differences in pharmacokinetics were observed, and standard dosing can be used 1
Severe hepatic impairment (Child-Pugh C): The effect on relugolix pharmacokinetics has not been evaluated, and use should be avoided 1
Mandatory Add-Back Therapy Considerations
Relugolix must be combined with low-dose estrogen and progestin (add-back therapy) to mitigate hypoestrogenic effects, regardless of renal or hepatic function:
Add-back therapy substantially reduces hot flashes, headaches, hypertension, and bone mineral density loss while maintaining therapeutic efficacy for bleeding control 2, 3
Without add-back therapy, mean BMD decreases by 4.9% over 24 weeks, making long-term monotherapy unsuitable 2
The combination regimen is FDA-approved specifically for fibroid-related heavy menstrual bleeding 3
Critical Clinical Pitfalls in Organ Dysfunction
Avoid these common errors when prescribing relugolix in patients with organ impairment:
Do not use in decompensated cirrhosis or severe hepatic impairment due to lack of pharmacokinetic data and potential for unpredictable drug metabolism 1
Do not use in end-stage renal disease requiring hemodialysis, as safety and efficacy have not been established 1
Do not prescribe relugolix monotherapy even in patients with organ dysfunction, as add-back therapy is essential to prevent severe hypoestrogenic complications including accelerated bone loss 2, 3
Monitor for drug interactions carefully in patients with hepatic or renal impairment who may be on multiple medications, as relugolix is a substrate of P-gp and CYP3A, and co-administration with combined P-gp and moderate CYP3A inhibitors increases relugolix exposure by 3.5-fold 1
Treatment Duration and Monitoring
Plan for finite treatment courses with appropriate monitoring:
Relugolix is commonly used for 3-4 months preoperatively to achieve maximal fibroid volume reduction (18-50% reduction) before myomectomy or hysterectomy 3, 4
For longer-term management up to 52 weeks, most women maintain bleeding reduction and stable bone mineral density when using combination therapy with add-back hormones 5
Cessation of therapy leads to rapid symptom recurrence, making relugolix unsuitable as a definitive long-term solution without add-back therapy 2, 3
Safety Profile Specific to Organ Dysfunction
The most common adverse effects remain consistent regardless of organ function:
Headaches and hot flashes are the most frequently reported side effects, occurring similarly across treatment groups 6, 5
Hypertension can develop during treatment and requires monitoring, particularly in patients with pre-existing renal impairment 2
Bone mineral density loss is dose-dependent and expected due to induced hypoestrogenic state, but is substantially mitigated with add-back therapy 7, 2