What is the recommended treatment and dosage of Myfembree (relugolix) for uterine fibroids in adult women?

Recommended Treatment and Dosage of Myfembree for Uterine Fibroids

Myfembree (relugolix combination therapy) is recommended at a dosage of 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate taken once daily as a fixed-dose combination tablet for the management of heavy menstrual bleeding associated with uterine fibroids in adult women. 1, 2

Mechanism of Action and Benefits

Myfembree works through a dual mechanism:

• Relugolix component: A GnRH receptor antagonist that competitively binds to GnRH receptors, reducing follicle-stimulating hormone and luteinizing hormone release, thereby decreasing estrogen and progesterone production 3
• Estradiol/norethindrone acetate components: Provide add-back hormone therapy that mitigates the hypoestrogenic side effects of relugolix alone, particularly bone mineral density loss and vasomotor symptoms 2, 3

Clinical Efficacy

The efficacy of Myfembree has been demonstrated in two pivotal phase 3 LIBERTY trials:

• Response rate: 71-73% of women achieved significant reduction in menstrual blood loss (volume <80 ml and ≥50% reduction from baseline) compared to only 15-19% with placebo 4
• Secondary benefits:
  • Significant improvement in amenorrhea rates
  • Reduced pain and distress from bleeding
  • Improved anemia
  • Decreased uterine volume
  • Enhanced quality of life 4

Treatment Algorithm for Uterine Fibroids

1. First-line options (for mild to moderate symptoms):

   • NSAIDs and tranexamic acid for menstrual bleeding
   • Hormonal contraceptives (estrogen-progestin oral contraceptives or progestin-containing IUDs) 1, 5

2. Second-line options (if inadequate response to first-line):

   • Myfembree (relugolix combination therapy) at 40 mg relugolix/1 mg estradiol/0.5 mg norethindrone acetate once daily 1, 2
   • Other GnRH antagonists or agonists with add-back therapy 1, 5

3. Procedural interventions (if medical management fails):

   • Uterine artery embolization (UAE)
   • MR-guided focused ultrasound (MRgFUS)
   • Myomectomy (hysteroscopic, laparoscopic, or open)
   • Hysterectomy (definitive treatment) 1, 5

Administration Guidelines

• Take one tablet once daily at approximately the same time
• Can be taken with or without food, but preferably before meals 3
• Treatment duration: FDA-approved for up to 24 months due to potential bone mineral density concerns with longer use 2

Monitoring Recommendations

1. Before initiating treatment:

   • Pregnancy test (contraindicated in pregnancy)
   • Blood pressure assessment
   • Baseline bone mineral density in patients with risk factors for osteoporosis

2. During treatment:

   • Monitor for hypoestrogenic effects (hot flushes, mood changes)
   • Blood pressure checks
   • Consider bone mineral density assessment for long-term use (>12 months)

Important Considerations and Cautions

• Bone health: Unlike GnRH agonist monotherapy, Myfembree preserves bone mineral density due to the estradiol/norethindrone acetate components 4
• Fertility: Treatment suppresses ovulation and fertility during use, but effects are reversible upon discontinuation 1, 3
• Symptom recurrence: Symptoms typically return after discontinuation of therapy 1
• Contraindications: Women with history of or at high risk for thromboembolic disorders, as estrogen component may increase risk 5

Emerging Research

Current research is exploring the use of Myfembree:

• As post-myomectomy therapy to delay fibroid recurrence and symptom return 6
• As preoperative therapy before laparoscopic myomectomy to reduce intraoperative blood loss 7

Myfembree represents a significant advance in the medical management of uterine fibroids, offering a convenient once-daily oral option that effectively controls symptoms while avoiding the significant bone loss associated with GnRH agonist monotherapy.