The use of Elagolix in Women with Liver and Kidney Impairments

The study provides insights about the safe daily dose of elagolix use in this group of women.

Key Points

Highlights:

• Elagolix should not be used in women with severe liver impairment, however, if necessary, it may be used in women with moderate liver impairment for up to 6 months at a dose of 150 mg/day.
• No dose adjustment is necessary for women with any degree of kidney impairment including those with end-stage kidney disease. 

Importance:

• The study provides insights about the use of elagolix, a newly approved medication for the treatment of endometriosis-associated pain, in a specific group of patients.

What's done here:

• Researchers analyzed data from two Phase 1 clinical trials assessing the safety and pharmacokinetics of elagolix in women with kidney and liver impairment compared to women with normal kidney and liver function. 

Key results:

• After Elagolix exposure liver functions were similar in women with normal liver function and those with mild liver impairment.
• After Elagolix exposure liver functions increased around threefold in women with moderate liver impairment and around sevenfold in women with severe liver impairment.
• After Elagolix exposure kidney functions were similar in women with normal kidney function and women with moderate and severe kidney impairment.

Limitations:

• Fewer women were enrolled in the moderate to severe kidney impairment group (a total of three) and the severe liver impairment group (a total of four) than initially intended in the trials but according to the authors this did not affect the conclusions of the study. 

Lay Summary

Elagolix may be used in women with moderate liver impairment, when necessary, for up to six months at a dose of 150 mg a day, according to a study published in the scientific journal Clinical Pharmacology in Drug Development. The medication should however not be used in women with severe liver impairment. No dose adjustment is necessary for women with any degree of kidney impairment including end-stage kidney disease.

Elagolix is an oral medication that has recently been approved by the U.S. Food and Drug Administration (FDA) to treat moderate to severe pain associated with endometriosis. It is a gonadotropin-releasing hormone (GnRH) antagonist or a molecule that blocks the effect of GnRH, a hormone produced by the brain that controls the secretion of sex hormones by the ovaries. By blocking the action of GnRH, elagolix halts the secretion of sex hormones such as estrogen, which is the main hormone that stimulates the abnormal growth of endometrial tissues outside the uterus.

The aim of the current study was to assess the safety and clearance of elagolix in women with kidney or liver impairment, the two main organs that play a crucial role in metabolizing toxins and medications.  Researchers analyzed data from two Phase 1 clinical trials that included women with liver and kidney impairment compared to women with normal liver and kidney function. The first study compared the effect of a single 150 mg dose of elagolix in women with liver impairment and women with normal liver function. The second looked at the effect of a single dose of 200 mg of elagolix in women with kidney impairment compared to women with normal kidney function. 

The researchers collected blood samples from the women and analyzed them pharmacokinetically. They found that the pharmacokinetic exposures of Elagolix were similar in women with normal kidney function and women with moderate and severe kidney impairment including those with end-stage kidney disease (also known as kidney failure). 

The pharmacokinetic exposures of elagolix were also similar in women with normal liver function and those with mild liver impairment. “The safety profile of a single elagolix 150 mg dose in women with [liver] impairment was acceptable,” the researchers wrote. However, they found that elagolix exposure increased around threefold in women with moderate liver impairment and around sevenfold in women with severe liver impairment. So they concluded that 150 mg of elagolix once a day is appropriate for use in women with moderate liver impairment for up to six months but it should not be used in women with severe liver impairment. 

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/30570832