ESTRADIOL/ NORETHINDRONE/ RELUGOLIX TAB

Clinical Criteria Summary

Monophasic pills with 30 mcg EE and desogestrel 0.15 mg: 21 active pills; 7 inert pills

Nuisance side effects associated with combination hormonal contraceptives may be managed by adjusting the estrogen/progestin content or ratio
Progestin-only products may be considered in patients with contraindications or a desire to avoid estrogen (general class guidance)

Listed on the VA National Formulary as generic components to allow for substitution of the least expensive equivalent product
Product availability varies and the listed products are not comprehensive

Diagnosis of endometriosis (clinical or surgical) in a premenopausal patient
Prescribed by or in consultation with a VA/VA Community Care Gynecology or Women’s Health Provider

Contraindication, intolerance, or inadequate response to one alternative treatment (e.g., NSAID, estrogen-containing or progestin-only hormonal contraceptive)
Assessed for history of suicidal ideation, depression, and mood disorders prior to starting treatment
Assessed for risk of bone density loss
Planned duration of treatment not to exceed a maximum of 24 months (due to risk for bone loss)

For patients who can become pregnant: Exclude pregnancy prior to receiving medication
For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective nonhormonal contraception during therapy

Monitor for mood changes and depressive symptoms after starting treatment
Baseline DXA (dual-energy X-ray absorptiometry) and periodic follow-up during treatment recommended
Consider risks and benefits of treatment in patients with history of low trauma fracture or risk factors for low bone density
If concomitant use of P-gp inhibitors is unavoidable, take the interacting medication at least 6 hours after relugolix

Prescribed by or in consultation with a VA/VA Community Care Gynecology or Women’s Health Provider
Confirmed diagnosis of uterine leiomyoma and heavy menstrual bleeding in a premenopausal patient
Contraindication, intolerance, or inadequate response to one alternative treatment (e.g., estrogen-progestin hormonal contraceptives, progestin-only contraceptives, tranexamic acid, etc.)

Assessed for history of suicidal ideation, depression, and mood disorders prior to starting treatment
Assessed for risk of bone density loss
Planned duration of treatment not to exceed a maximum of 24 months (due to risk for bone loss)
Baseline DXA (dual-energy X-ray absorptiometry) and periodic follow-up during treatment recommended; consider risks and benefits in patients with history of low trauma fracture or risk factors for low bone density
Monitor for mood changes and depressive symptoms after starting treatment

For patients who can become pregnant: Exclude pregnancy prior to receiving REN
For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective nonhormonal contraception during therapy
If concomitant P-gp inhibitor use is unavoidable, take the interacting medication at least 6 hours after REN

Management of heavy menstrual bleeding (HMB) associated with uterine leiomyomas (fibroids) in premenopausal women
Management of moderate to severe pain associated with endometriosis in premenopausal women

Fixed-dose combination oral tablet containing 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate
One tablet orally daily at the same time each day
Initiate as soon as possible and within 7 days after the start of menses
Treatment duration limited to 24 months due to risk of bone loss that may not be reversible

Exclude pregnancy prior to starting treatment; discontinue hormonal contraceptives before initiation
Perform pregnancy testing during treatment if pregnancy is suspected; discontinue if confirmed
Advise use of effective non-hormonal contraception during treatment and for one week after discontinuation
Avoid concomitant use of estrogen-containing hormonal contraceptives
Baseline assessment of bone mineral density (BMD) by DXA recommended; follow-up DXA annually during treatment for endometriosis and periodically during treatment for fibroids
Monitor blood pressure; contraindicated in uncontrolled hypertension, monitor in patients with controlled hypertension
Evaluate patients with history of mood disorders and/or suicidal ideation before initiating; monitor for mood changes and depressive symptoms after initiation
Advise women with submucosal uterine fibroids about possible prolapse or expulsion; seek medical attention for severe bleeding or cramping
Consider discontinuation if hair loss (alopecia) becomes a concern
Monitor for risk of early pregnancy loss, vasomotor symptoms (hot flushes), mood disorders including depression and suicidal ideation, hypertension, abdominal pain, decreased libido, abnormal uterine bleeding, nausea, and hypersensitivity reactions (anaphylactoid reactions, urticaria, angioedema)