General Information

Oriahnn is a combination of elagolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, estradiol, an estrogen, and norethindrone acetate, a progestin.

Oriahnn is specifically indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.

Oriahnn is supplied as a capsule for oral administration. Exclude pregnancy before starting Oriahnn or start Oriahnn within 7 days from the onset of menses. The recommended dosage of Oriahnn is:

• One elagolix 300 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg capsule in the morning (AM), and
• One elagolix 300 mg capsule in the evening (PM).

Take the morning and evening capsules at approximately the same time each day, with or without food. The recommended duration of treatment with Oriahnn is 24 months.

Mechanism of Action

Oriahnn combines elagolix and estradiol/norethindrone acetate (E2/NETA), a combination of estrogen and progestin.

• Elagolix is a GnRH receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland. Administration of elagolix results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones estradiol and progesterone and reduces bleeding associated with uterine fibroids.
• E2 acts by binding to nuclear receptors that are expressed in estrogen-responsive tissues. As a component of Oriahnn, the addition of exogenous estradiol may reduce the increase in bone resorption and resultant bone loss that can occur due to a decrease in circulating estrogen from elagolix alone.
• Progestins such as NETA act by binding to nuclear receptors that are expressed in progesterone responsive tissues. As a component of Oriahnn, NETA may protect the uterus from the potential adverse endometrial effects of unopposed estrogen.

Side Effects

Adverse effects associated with the use of Oriahnn may include, but are not limited to, the following:

• hot flushes
• headache
• fatigue
• metrorrhagia

The Oriahnn drug label comes with the following Black Box Warning: THROMBOEMBOLIC DISORDERS AND VASCULAR EVENTS  Estrogen and progestin combinations, including Oriahnn, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism, deep vein thrombosis, stroke and myocardial infarction, especially in women at increased risk for these events. Oriahnn is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke and women with uncontrolled hypertension.

Clinical Trial Results

The FDA approval of Oriahnn was based on two, randomized Phase 3 uterine fibroid clinical trials, ELARIS UF-I and ELARIS UF-II, ORIAHNN achieved the primary endpoint of clinically meaningful reduction in bleeding (defined as the proportion of women who achieved both at least a 50 percent reduction in menstrual blood loss at final month of treatment and a total menstrual blood loss amount of less than 80 ml), compared with placebo in final month of study for patients, with seven out of 10 women no longer experiencing heavy menstrual bleeding versus one out of 10 women on placebo. Oriahnn also reduced heavy menstrual bleeding due to uterine fibroids by 50 percent within the first month of use.