Orilissa

Uses

Orilissa is used for the management of moderate to severe pain associated with endometriosis.

• No dose adjustment of Orilissa is required in women with any degree of renal impairment or end-stage renal disease (including women on dialysis)
• No dosage adjustment of Orilissa is required in women with mild hepatic impairment.
• Safety and effectiveness of Orilissa in patients less than 18 years of age have not been established.

Orilissa is also used to associated treatment for these conditions: Heavy Menstrual Bleeding, Moderate Endometriosis related pain, Severe Endometriosis related pain

How Orilissa works

Endometriosis develops when tissue that is similar to the kind that is normally located in the uterus starts to grow outside of the uterus . Such growth leads to various symptoms like pain during periods, pelvic pain between periods, and pain during sexual intercourse . The growths themselves are referred to as lesions and frequently develop on the ovaries, fallopian tubes, and other areas around the uterus, including the bowel or bladder . The growth of these lesions is dependent upon the estrogen hormone .

Orilissa is an orally-administered, nonpeptide small molecule gonadotropin-releasing hormone (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.

Dosage

Orilissa dosage

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.

Initiate treatment with Orilissa 150 mg once daily-

• Maximum Treatment Duration: 24 months
• Coexisting Condition: None

• Maximum Treatment Duration: 6 months
• Coexisting Condition: Dyspareunia

• Maximum Treatment Duration: 6 months
• Coexisting Condition: Moderate hepatic impairment (Child-Pugh Class B)

Side Effects

Most common adverse reactions (>5%) in clinical trials included hot flushes and night sweats, headache, nausea, insomnia, amenorrhea, anxiety, arthralgia, depression-related adverse reactions and mood changes.

Toxicity

In case of overdose, monitor the patient for any signs or symptoms of adverse reactions and initiate appropriate symptomatic treatment, as needed . Common adverse reactions of elagolix include hot flush, headache, nausea, insomnia, mood alterations, amenorrhea, depression, anxiety, arthralgia, bone loss, changes in menstrual bleeding patterns, suicidal ideation and behavior, exacerbation of existing mood disorders, and/or hepatic transaminase elevations .

The recommended duration of use for elagolix is up to 24 months for the 150 mg once daily dose and up to six months for the 200 mg twice daily dose, as it 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 . For women with moderate hepatic impairment, the recommended dosage is 150 mg once daily for up to six months .

Precaution

• Bone Loss: Dose- and duration-dependent decreases in bone mineral density (BMD) that may not be completely reversible. Assess BMD in women with additional risk factors for bone loss
• Reduced Ability to Recognize Pregnancy: Orilissa may alter menstrual bleeding, which may reduce the ability to recognize pregnancy. Perform testing if pregnancy is suspected. Discontinue if pregnancy is confirmed
• Suicidal Ideation and Mood Disorders: Advise patients to seek medical attention for suicidal ideation, suicidal behavior, new onset or worsening depression, anxiety, or other mood changes
• Hepatic Transaminase Elevations: Dose-dependent elevations in serum alanine aminotransferase (ALT). Counsel patients on signs and symptoms of liver injury
• Potential for Reduced Efficacy with Estrogen-Containing Contraceptives: Use non-hormonal contraception during treatment and for one week after discontinuing Orilissa.

Food Interaction

• Administer calcium supplement. This will minimize the risk of bone mineral density loss.
• Administer vitamin supplements. Administer Vitamin D supplements to minimize the risk of bone mineral density loss.
• Take at the same time every day.
• Take with or without food.

Orilissa Drug Interaction

Unknown: dicyclomine, acetazolamide, lamotrigine, acetaminophen, sertraline

Orilissa Disease Interaction

Major: hepatic impairment, osteoporosisModerate: depression/anxiety

Volume of Distribution

The apparent volume of distribution at steady state (Vdss/F) of elagolix is reported to be 1674 for a 150 mg daily regimen and 881 for a 200 mg twice daily regimen .

Elimination Route

The Tmax of elagolix is reported as being 1.0 hours . The effect of a high-fat meal (relative to fasting) can result in a reduction of the AUC and Cmax by as much as 24% and 36%, respectively .

Half Life

The terminal phase elimination half-life of elagolix is recorded as being 4 to 6 hours .

Clearance

The oral clearance (CL/F) of elagolix is 123 L/hr for a 150 mg once daily regimen and 144 L/hr for a 200 mg twice daily regimen .

Elimination Route

The primary route of elimination of elagolix is via hepatic metabolism .

Pregnancy & Breastfeeding use

Exposure to Orilissa early in pregnancy may increase the risk of early pregnancy loss. Use of Orilissa is contraindicated in pregnant women. Discontinue Orilissa if pregnancy occurs during treatment. The limited human data with the use of Orilissa in pregnant women are insufficient to determine whether there is a risk for major birth defects or miscarriage. Although two cases of congenital malformations were reported in clinical trials with Orilissa, no pattern was identified and miscarriages were reported at a similar incidence across treatment groups. There is no information on the presence of elagolix or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production.

There are no adequate animal data on the excretion of Orilissa in milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Orilissa and any potential adverse effects on the breastfed child from Orilissa.

Contraindication

Orilissa is contraindicated in women:

• Who are pregnant
• 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
• With severe hepatic impairment because of the risk of bone loss
• With concomitant use of strong organic anion transporting polypeptide (OATP) 1B1 inhibitors (e.g., cyclosporine and gemfibrozil)

Storage Condition

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Innovators Monograph

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