ESTRADIOL/ NORETHINDRONE/ RELUGOLIX TAB
Clinical Criteria Summary
Document 338: Contraceptive Agents Hormonal on VA National Formulary
Criteria for Combination Hormonal Contraceptive Pills
- Desogestrel/Ethinyl Estradiol (and other Monophasic pills with 20 mcg EE)
- Indication/Use: Highly effective in preventing pregnancy when used as directed.
- Regimen: 21 active pills; 7 inert pills.
- Monophasic pills with 30 mcg EE (includes Drospirenone/Ethinyl Estradiol, Norethindrone/Ethinyl Estradiol)
- Regimen: 21 active pills; 7 inert pills.
- Monophasic pills with 35 mcg EE (includes Norethindrone/Ethinyl Estradiol, Norgestimate/Ethinyl Estradiol)
- Regimen: 21 active pills; 7 inert pills.
- Extended Cycle Pills (Levonorgestrel/Ethinyl Estradiol 30 mcg)
- Regimen: 84 active pills; 7 inert pills.
- Management of nuisance side effects: Adjust estrogen/progestin content or ratio.
Criteria for Progestin-Only Pills
- Indication/Use: Considered in patients with contraindications to estrogen or a desire to avoid estrogen.
- Drug: Norethindrone 0.35 mg (Camila, Errin, Heather, Micronor, Incassia, Jencycla, Nor-QD, Eluryng)
- Regimen: Active pill daily continuously; no inert pills.
Criteria for Non-Oral Hormonal Contraceptives
- Indication/Use: Useful for patients with compliance issues that do not require daily dosing.
- Vaginal Ring (EE 15 mcg/day + Etonogestrel)
- Regimen: 1 ring inserted for 3 wks, 1 wk off.
- Transdermal Patch (EE 35 mcg + Norelgestromin 150 mcg/day)
- Regimen: 1 patch used for 3 wks, 1 wk off.
- Injection (Medroxyprogesterone acetate 150 mg IM or 104 mg SQ)
- Regimen: 1 injection Q3 mos (13 wks or 12 to 14 wks).
- Note: Self-administration of SQ DMPA is a safe and effective alternative; may be offered in the context of shared decision making.
Criteria for Emergency Contraception
- Levonorgestrel 1.5 mg (Aftera, My Choice, My Way, Plan B One-Step, Next Choice, Opcicon, Take Action)
- Regimen: 1 pill x1.
- Ulipristal 30 mg (ella)
- Regimen: 1 pill x1.
Criteria for Long-Acting Reversible Contraceptives (IUDs & Implants)
- Levonorgestrel IUD (52 mg, 19.5 mg, 13.5 mg)
- Duration: Up to 8 yrs, up to 5 yrs, or up to 3 yrs respectively.
- Non-hormonal Copper IUD (Paragard)
- Duration: Up to 10 yrs.
- Etonogestrel Implant (Nexplanon)
- Duration: Up to 5 yrs.
Formulary & Dispensing Criteria
- All contraceptives are listed on the National Formulary as generic components to allow substitution of the least expensive equivalent product.
- 12-month dispensing prerequisites: 1) Stable on product for at least 3 mos; 2) Contraceptive is on CMOP greater than 90-day supply list; and 3) Patient accepts copay burden, if applicable.
Document 582: Relugolix Estradiol Norethindrone MYFEMBREE Endometriosis Criteria Mar 2024
Indication & Patient Population
- 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
Exclusion Criteria
- High risk or history of arterial, venous thrombotic, or thromboembolic disorder
- Pregnancy
- Known osteoporosis
- Uncontrolled hypertension
- Current or history of breast cancer or other hormonally sensitive malignancies
- Known hepatic impairment or disease
- Undiagnosed abnormal uterine bleeding
- Concomitant use of hormonal contraceptives
- Concomitant use of P-glycoprotein (P-gp) inhibitors
- Concomitant use of combined P-gp and strong CYP3A inducers
- Any additional contraindication to receiving estrogen and/or progestin
- Known hypersensitivity to relugolix, estradiol, or norethindrone
Inclusion Criteria
- 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)
Additional Patient-Specific Requirements
- 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
Monitoring & Safety Requirements
- 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
Document 583: Relugolix Estradiol Norethindrone MYFEMBREE Fibroid Criteria Mar 2024
Indication
- Heavy Menstrual Bleeding Associated with Uterine Leiomyomas (Fibroids)
Exclusion Criteria
- High risk or history of arterial, venous thrombotic, or thromboembolic disorder
- Pregnancy
- Known osteoporosis
- Uncontrolled hypertension
- Current or history of breast cancer or other hormonally sensitive malignancies
- Known hepatic impairment or disease
- Undiagnosed abnormal uterine bleeding
- Concomitant use of hormonal contraceptives
- Concomitant use of P-glycoprotein (P-gp) inhibitors
- Concomitant use of combined P-gp and strong CYP3A inducers
- Any additional contraindication to receiving estrogen and/or progestin
- Known hypersensitivity to relugolix, estradiol, or norethindrone
Inclusion Criteria
- 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.)
Monitoring & Duration Requirements
- 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
Counseling & Safety Precautions
- 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
Document 591: MON Relugolix Estradiol Norethindrone MYFEMBREE Monograph Mar 2024
Indications
- 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
Patient Population
- Premenopausal women
Dosing & Administration
- 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
Contraindications
- Pregnancy
- Known osteoporosis
- Known hepatic impairment or hepatic disease
- High risk of arterial, venous thrombotic, or thromboembolic disorder
- Current or history of breast cancer or other hormone-sensitive malignancies
- Undiagnosed abnormal uterine bleeding
- Known hypersensitivity to ingredients
- Uncontrolled hypertension
Monitoring & Precautions
- 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)
Source Documents
Document 338: Contraceptive Agents Hormonal on VA National Formulary
Document 582: Relugolix Estradiol Norethindrone MYFEMBREE Endometriosis Criteria Mar 2024
Document 583: Relugolix Estradiol Norethindrone MYFEMBREE Fibroid Criteria Mar 2024
Document 591: MON Relugolix Estradiol Norethindrone MYFEMBREE Monograph Mar 2024