Orilissa From AbbVie Inc

The FDA has approved orilissa (elagolix; AbbVie Inc) to manage moderate to severe pain associated with endometriosis.¹

Endometriosis occurs when tissue similar to that which normally lines the uterus begins to grow outside the uterus, often on the bladder, the bowel, the fallopian tubes, or the ovaries. Symptoms include dysmenorrhea, dyspareunia, and pelvic pain in between menses. About 10% of American women aged 15 to 49 years are affected by endometriosis. Pain management medications for endometriosis often consist of hormonal therapies, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and oral contraceptives. Orilissa is the first and only oral gonadotropin-releasing hormone (GnRH) receptor antagonist to receive approval for endometriosis.²

PHARMACOLOGY AND PHARMACOKINETICS

Orilissa inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland, leading to a dose-dependent suppression of follicle-stimulating hormone and luteinizing hormone. This results in decreased blood concentrations of estradiol and progesterone.

Orilissa reaches maximum plasma concentration about 1 hour after oral administration and has a half-life of 4 to 6 hours. Its major metabolism pathway is CYP3A, with minor pathways including CYP2C8, CYP2D6, and uridine glucuronosyltransferases. Its major route of elimination is hepatic.¹

DOSAGE AND ADMINISTRATION

A negative pregnancy test should be obtained before starting Orilissa. Alternatively, treatment may begin within 7 days from the onset of menses. Patients with mild hepatic impairment or normal liver function should use Orilissa 150 mg orally once daily for up to 24 months or 200 mg orally twice daily for up to 6 months. Patients with moderate hepatic impairment should use Orilissa 150 mg orally once daily for up to 6 months. Orilissa should not be used by patients with severe hepatic impairment. Dose adjustment is not required with any degree of renal impairment or end-stage renal disease, including dialysis. The medication should be taken at about the same time each day, with or without food.¹

CLINICAL TRIALS

The efficacy of Orilissa 150 mg daily and 200 mg twice daily was evaluated in 2 double-blind, multinational, placebo-controlled trials of 1686 premenopausal women. The co-primary efficacy end points were the proportion of patients whose dysmenorrhea responded to treatment and the proportion of those whose nonmenstrual pelvic pain responded to treatment. A responder was defined as a patient who experienced a reduction in dysmenorrhea and nonmenstrual pelvic pain without increasing their use of an analgesic, either an NSAID or an opioid, for endometriosis-associated pain. At the third month of the study, a higher proportion of patients using Orilissa 150 mg once daily or 200 mg twice daily reported a dose-dependent reduction in their dysmenorrhea and nonmenstrual pelvic pain compared with those using placebo.

Patients using Orilissa 150 mg once daily or 200 mg twice daily showed statistically significant greater mean decreases from baseline in dysmenorrhea and nonmenstrual pelvic pain scores at 6 months of treatment than those using a placebo. The secondary end point was dyspareunia associated with endometriosis. In both trials, those using Orilissa 200 mg twice daily showed a statistically significant greater reduction in dyspareunia at month 3 than placebo takers.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

The use of Orilissa is contraindicated in patients who are preg- nant, have known osteoporosis, with severe hepatic impairment, or in those who are using strong organic anion transporting polypeptide 1B1 inhibitors, such as cyclosporine or gemfibrozil.

Orilissa causes a dose-dependent decrease in bone mineral density (BMD). This loss is greater with increasing duration of use and may not be completely reversible, even after stopping treatment. BMD should be assessed in women with additional risk factors for bone loss. Treatment with Orilissa may alter menstrual bleeding, which may reduce the ability to recognize pregnancy. A pregnancy test should be done if pregnancy is suspected, and if the test is positive, Orilissa should be discontinued. Patients should be counseled to seek medical attention if new or worsening anxiety, depression, mood changes, or suicidal behavior or ideation occurs while using Orilissa. Because dose-dependent elevations in serum alanine aminotransferase may occur while using Orilissa, patients should be counseled regarding the signs and symptoms of liver injury. Orilissa may decrease the efficacy of estrogen-containing contraceptives.

Nonhormonal contraception should be used during treatment and for 1 week after stopping treatment. The effectiveness and safety of Orilissa in patients younger than 18 years have not been established. The most common adverse reactions (incidence, >5%) included amenorrhea, anxiety, arthralgia, depression-related reactions, headache, hot flushes, insomnia, mood changes, nausea, and night sweats.¹

Monica Holmberg, PharmD, BCPS, earned her PharmD at the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Health Care System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.

REFERENCES

• Orilissa [prescribing information]. North Chicago, IL: AbbVie Inc; 2018. rxabbvie .com/pdf/orilissa_pi.pdf. Accessed November 1, 2018.
• AbbVie receives U.S. FDA approval of Orilissa (elagolix) for the management of moderate to severe pain associated with endometriosis [news release]. North Chicago, IL: AbbVie Inc; July 24, 2018. news.abbvie.com/news/abbvie-receives-us-fda- approval-orilissa-elagolix-for-management-moderate-to-severe-pain-associat- ed-with-endometriosis.htm. Accessed November 1, 2018.