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Medication Spotlight: Orilissa

Abbvie has two marketed products for endometriosis - one of them is Lupron and the other is the newly approved Orilissa. There is something interesting about Orilissa!

Orilissa (elagolix) is a gonadotropin releasing hormone (GnRH) receptor antagonist which is used for moderate to severe pain related to endometriosis. As an antagonist in the pituitary gland, this leads to a reduction in FSH and LH secretion, resulting in a decrease in estrogen and progesterone levels. These hormones are involved in the symptoms of endometriosis. Role in Therapy:

Orilissa is called a second generation GnRH antagonist because it offers multiple advantages. It is a small non-peptide molecule, compared to the other agents which are proteins similar in structure to the GnRH. Secondly, it is administered as an oral agent, compared to intramuscular injections. Third, it is fast acting, with quick suppression of FSH and LH within hours. Lastly, this medication is a GnRH antagonist, which does not cause a symptom flare seen with GnRH agonists. Dosing: flexible as 150 mg once daily or 200 mg twice daily. It can be taken with or without food. Pregnancy: Patients should be screened for pregnancy prior to initiation because it can cause fetal abnormalities. Patients should use contraception (only progestin or non-hormonal methods). If patients become pregnant during treatment, it can be discontinued quickly with reversal in days, compared to Lupron which takes weeks. Adverse Effects: Orilissa causes a dose-dependent reduction in bone density; thus patients should be screened for osteoporosis and be taking calcium plus vitamin D (hence contraindicated if confirmed). Orilissa can cause elevated liver enzymes due to hepatic metabolism (hence contraindicated in severe liver disease). Other adverse effects include amenorrhea, hot flushes, headache, nausea and mood swings. Drug Interactions: Orilissa is a CYP3A4 substrate, which requires a dose reduction in the presence of strong inhibitors. It is also an OATP1B1 substrate, so it is contraindicated with inhibitors such as cyclosporine and gemfibrozil. Orilissa itself is also a pg-p inhibitor and CYP3A4 inducer (which makes it a little messy).

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