Chronic overdosage of elagolix may result in greater suppression of estradiol levels and a consequent increased risk of bone loss with long-term therapy. Interactions
Elagolix has a number of potential drug interactions with other medications. Elagolix is a substrate of the cytochrome P450 (CYP450) enzyme CYP3A, and inhibitors and inducers of CYP3A4 may alter the metabolism of elagolix and increase or decrease its circulating levels. The strong CYP3A4 inhibitor ketoconazole has been found to increase peak levels of and total exposure to a single 150 mg dose of elagolix by about 2-fold. Paradoxically, rifampin, a strong inducer of CYP3A4 and other CYP450 enzymes, increased peak levels of and total exposure to a single 150 mg dose of elagolix as well. A single dose of rifampin increased peak levels of elagolix by 4.4-fold and total exposure by 5.6-fold, whereas continuous rifampin therapy increased peak levels of elagolix by 2-fold and total exposure by 1.7-fold. The use of elagolix at 200 mg twice per day concomitantly with rifampin is not recommended, whereas the concomitant use of elagolix at 150 mg once per day with rifampin should be limited to 6 months. No significant changes in exposure to elagolix were observed with concomitant administration of rosuvastatin (a substrate of OATP1B1, OATP1B3, and BCRP), sertraline (a moderate inhibitor of CYP2D6 and CYP2B6), or fluconazole (a strong inhibitor of CYP2C19 and a moderate inhibitor of CYP2C9 and CYP3A4).Elagolix is a substrate of the hepatic OATP1B1 transporter.
People taking elagolix with new or existing depressive symptoms should be promptly evaluated to determine whether the benefits of treatment outweigh the risks. In those with new or existing depressive symptoms, referral to a mental health professional, as appropriate, may be warranted. Immediate medical attention should be sought for those with suicidal ideation and behavior.Elagolix dose-dependently produced elevated liver enzymes, including elevations of serum alanine aminotransferase of at least 3-fold the upper limit, in clinical trials. This was observed in one woman (0.2%) with 150 mg once per day and in five women (1.1%) with 200 mg twice per day, compared to one woman (0.1%) given placebo. Medical attention should be sought if signs or symptoms of liver injury, such as jaundice, are noticed. The lowest effective dosage of elagolix may be used to minimize the risk of liver problems, and in those who develop elevated liver enzymes during elagolix therapy, prompt evaluation should be done to determine whether the benefits of treatment outweigh the risks. Overdose
In the event of an overdose of elagolix, the person should be monitored for any signs or symptoms of adverse reactions and should be treated on a symptomatic basis as needed. Elagolix has been assessed in clinical studies at a dose as high as a single administration of 1,200 mg, which resulted in concentrations of the medication that were 17 times higher than with the typical high clinical dosage of 200 mg twice per day. No adverse effects were mentioned.