Oriahnn

ORIAHNN- elagolix and estradiol and norethisterone
AbbVie Inc.

1 INDICATIONS AND USAGE

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

Limitation of Use:

Use of ORIAHNN should be limited to 24 months due to the risk of continued bone loss, which may not be reversible [see Dosage and Administration ( 2.1) and Warnings and Precautions ( 5.2) ].

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosing Information

• Exclude pregnancy before starting ORIAHNN or start ORIAHNN within 7 days from the onset of menses [see Use in Specific Populations ( 8.1) and ( 8.3) ].

• 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 [see Warnings and Precautions ( 5.2) ].

2.2 Missed Dose

Instruct the patient to take the missed dose of ORIAHNN within 4 hours of the time that it was supposed to be taken and then the next dose at the usual time. If more than 4 hours have passed since a capsule is usually taken, instruct the patient not to take the missed dose and take the next dose at the usual time. Take only one morning capsule and one evening capsule per day.

3 DOSAGE FORMS AND STRENGTHS

ORIAHNN consists of two capsules:

• The morning (AM) capsule is white and yellow, printed with “EL300 AM” containing 300 mg elagolix, 1 mg estradiol, and 0.5 mg norethindrone acetate.
• The evening (PM) capsule is white and light blue, printed with “EL300 PM” containing 300 mg elagolix.

4 CONTRAINDICATIONS

ORIAHNN is contraindicated in women:

• With a high risk of arterial, venous thrombotic, or thromboembolic disorders [see Boxed Warning and Warnings and Precautions ( 5.1) ]. Examples include women over 35 years of age who smoke, and women who are known to have:

  ○ current or history of deep vein thrombosis or pulmonary embolism

  ○ vascular disease (e.g., cerebrovascular disease, coronary artery disease, peripheral vascular disease)

  ○ thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation)

  ○ inherited or acquired hypercoagulopathies

  ○ uncontrolled hypertension

  ○ headaches with focal neurological symptoms or have migraine headaches with aura if over age 35

• Who are pregnant. Exposure to ORIAHNN early in pregnancy may increase the risk of early pregnancy loss [see Use in Specific Populations ( 8.1) ].

• With known osteoporosis because of the risk of further bone loss [see Warnings and Precautions ( 5.2) ].

• With current or history of breast cancer or other hormonally-sensitive malignancies, and with increased risk for hormonally-sensitive malignancies [see Warnings and Precautions ( 5.3) ].

• With known hepatic impairment or disease [see Warnings and Precautions ( 5.5) ].

• With undiagnosed abnormal uterine bleeding.

• With known anaphylactic reaction, angioedema, or hypersensitivity to ORIAHNN or any of its components.

• Taking inhibitors of organic anion transporting polypeptide (OATP)1B1 (a hepatic uptake transporter) that are known or expected to significantly increase elagolix plasma concentrations [see Drug Interactions ( 7.2) ].

5 WARNINGS AND PRECAUTIONS

5.1 Thromboembolic Disorders and Vascular Events

ORIAHNN is contraindicated in women with current or history of thrombotic or thromboembolic disorders and in women at increased risk for these events [see Contraindications ( 4) ]. In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3), two thrombotic events occurred in 453 ORIAHNN-treated women (thrombosis in the calf and pulmonary embolism) [see Adverse Reactions ( 6.1) and Clinical Studies ( 14) ]. Estrogen and progestin combinations, including the estradiol/norethindrone acetate component of ORIAHNN, increase the risk of thrombotic or thromboembolic disorders, including pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at high risk for these events. In general, the risk is greatest among women over 35 years of age who smoke, and women with uncontrolled hypertension, dyslipidemia, vascular disease, or obesity.

Discontinue ORIAHNN if an arterial or venous thrombotic, cardiovascular, or cerebrovascular event occurs or is suspected. If feasible, discontinue ORIAHNN at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.

Stop ORIAHNN immediately if there is sudden unexplained partial or complete loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis as these have been reported in patients receiving estrogens and progestins.

5.2 Bone Loss

ORIAHNN is contraindicated in women with known osteoporosis [see Contraindications ( 4)]. ORIAHNN may cause a decrease in bone mineral density (BMD) in some patients. BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment [see Adverse Reactions ( 6.1) ].

In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3) [see Clinical Studies ( 14) ] , seven out of 453 (1.5%) ORIAHNN-treated women experienced fractures, including one (0.2%) with a fragility fracture, compared to one out of 196 (0.5%) placebo-treated women (patient had a non-fragility fracture). Five of the seven ORIAHNN-treated women reported these fractures in the post-treatment follow-up period. The impact of BMD decreases on long-term bone health and future fracture risk in premenopausal women is unknown.

Consider the benefits and risks of ORIAHNN treatment in patients with a history of a low-trauma fracture or other risk factors for osteoporosis or bone loss, including taking medications that may decrease BMD (e.g., systemic or chronic inhaled corticosteroids, anticonvulsants, or proton pump inhibitors).

Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and periodically thereafter. Consider discontinuing ORIAHNN if the risk associated with bone loss exceeds the potential benefit of treatment. Limit the duration of use to 24 months to reduce the extent of bone loss [see Indications and Usage ( 1) and Dosage and Administration ( 2.1) ].

Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation for patients with inadequate dietary intake may be beneficial.