Orilissa

ORILISSA- elagolix sodium tablet, film coated
AbbVie Inc.

1 INDICATIONS AND USAGE

ORILISSA is indicated for the management of moderate to severe pain associated with endometriosis.

Limitation s of Use:

Limit the duration of use based on the dose and coexisting condition (see Table 1) [see D osage and Administration ( 2.1) and Warnings and Precautions ( 5.1) ].

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosing Information

• Exclude pregnancy before starting ORILISSA or start ORILISSA within 7 days from the onset of menses.
  
• Take ORILISSA at approximately the same time each day, with or without food.
  
• Use the lowest effective dose, taking into account the severity of symptoms and treatment objectives [see Warnings and Precautions ( 5.1, 5.3, 5.4) and Clinical Studies ( 14)].
• Limit the duration of use because of bone loss (Table 1) [see Warnings and Precautions ( 5.1)].

Table 1. Recommended Dosage and Duration of Use

Dosing Regimen	Maximum Treatment Duration	Coexisting Condition
Initiate treatment withORILISSA 150 mg once daily	24 months	None
Consider initiating treatment with ORILISSA 200 mg twice daily	6 months	Dyspareunia
Initiate treatment with ORILISSA150 mg once daily. Use of 200 mgtwice daily is not recommended.	6 months	Moderate hepatic impairment (Child-Pugh Class B)

2.2 Hepatic Impairment

No dosage adjustment of ORILISSA is required in women with mild hepatic impairment (Child-Pugh A).

Compared to women with normal liver function, those with moderate hepatic impairment had approximately 3-fold higher elagolix exposures and those with severe hepatic impairment had approximately 7-fold higher elagolix exposures. Because of these increased exposures and risk for bone loss:

• ORILISSA 150 mg once daily is recommended for women with moderate hepatic impairment (Child-Pugh B) with the duration of treatment limited to 6 months. Use of ORILISSA 200 mg twice daily is not recommended for women with moderate hepatic impairment [see Use in Specific Populations ( 8.7) and Clinical Pharmacology ( 12.3)].
  
• ORILISSA is contraindicated in women with severe hepatic impairment (Child-Pugh C) [see Contraindications ( 4), Use in Specific Populations ( 8.7) and Clinical Pharmacology ( 12.3)].

2.3 Missed Dose

Instruct the patient to take a missed dose of ORILISSA on the same day as soon as she remembers and then resume the regular dosing schedule.

• 150 mg once daily: take no more than 1 tablet each day.
  
• 200 mg twice daily: take no more than 2 tablets each day.

3 DOSAGE FORMS AND STRENGTHS

The 150 mg tablets are light pink, oblong, film-coated tablets with “EL 150” debossed on one side. Each tablet contains 155.2 mg of elagolix sodium equivalent to 150 mg of elagolix.

The 200 mg tablets are light orange, oblong, film-coated tablets with “EL 200” debossed on one side. Each tablet contains 207.0 mg of elagolix sodium equivalent to 200 mg of elagolix.

4 CONTRAINDICATIONS

ORILISSA is contraindicated in women:

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

● With known osteoporosis because of the risk of further bone loss [see Warnings and Precautions ( 5.1)]

● With severe hepatic impairment [see Use in Specific Populations ( 8.7), Clinical Pharmacology ( 12.3)]

● 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)]

● With known hypersensitivity reaction to ORILISSA or any of its inactive components. Reactions have included anaphylaxis and angioedema [see Adverse Reactions ( 6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Bone Loss

ORILISSA causes a dose-dependent decrease in bone mineral density (BMD). BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment [see Adverse Reactions ( 6.1)]. The impact of these BMD decreases on long-term bone health and future fracture risk are unknown.

ORILISSA is contraindicated in women with known osteoporosis [see Contraindications ( 4)]. Consider assessment of BMD in patients with a history of a low-trauma fracture or other risk factors for osteoporosis or bone loss. Limit the duration of use to reduce the extent of bone loss [see Dosage and Administration ( 2.2)]. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients.

5.2 Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize Pregnancy

Women who take ORILISSA may experience a reduction in the amount, intensity or duration of menstrual bleeding, which may reduce the ability to recognize the occurrence of a pregnancy in a timely manner [see Adverse Reactions ( 6.1)]. Perform pregnancy testing if pregnancy is suspected, and discontinue ORILISSA if pregnancy is confirmed.

5.3 Suicidal Ideation, Suicidal Behavior, and Exacerbation of Mood Disorders

Suicidal ideation and behavior, including one completed suicide, occurred in subjects treated with ORILISSA in the endometriosis clinical trials. ORILISSA subjects had a higher incidence of depression and mood changes compared to placebo, and ORILISSA subjects with a history of suicidality or depression had a higher incidence of depression compared to subjects without such a history [see Adverse Reactions ( 6.1)]. Promptly evaluate patients with depressive symptoms to determine whether the risks of continued therapy outweigh the benefits [see Adverse Reactions ( 6.1)]. Patients with new or worsening depression, anxiety or other mood changes should be referred to a mental health professional, as appropriate. Advise patients to seek immediate medical attention for suicidal ideation and behavior. Reevaluate the benefits and risks of continuing ORILISSA if such events occur.