But the combination carries a Boxed Warning, and a litany of risks

WASHINGTON —The FDA approved an oral elagolix, estradiol, and norethindrone acetate combination (Oriahnn) to treat heavy menstrual bleeding in premenopausal women with fibroids.

“Uterine fibroids are the most common benign tumors affecting premenopausal women, and one of the most common symptoms from fibroids is heavy menstrual bleeding,” said Christine P. Nguyen, MD, Acting Director, Division of Urology, Obstetrics and Gynecology in FDA’s Center for Drug Evaluation and Research, in a statement. “Although surgical treatments, such as hysterectomy, are available, patients may not qualify for surgery or want the procedure. Various non-surgical therapies are used to treat fibroid-related heavy menstrual bleeding, but none have been FDA-approved specifically for this use. Today’s approval provides an FDA-approved medical treatment option for these patients.”

This approval was based on the results of two clinical trials including 591 premenopausal women with heavy menstrual bleeding due to fibroids. Participants were randomized to receive elagolix, estradiol, and norethindrone capsules or placebo for six months.

“Heavy menstrual bleeding at baseline was defined as having at least two menstrual cycles with greater than 80 mL (about a third of a cup) of menstrual blood loss (MBL),” the FDA explained. “The primary endpoint was the proportion of women who achieved MBL volume less than 80 mL at the final month and 50% or greater reduction in MBL volume from the start of the study (baseline) to the final month. In the first study, 68.5% of patients who received [the combination] achieved this endpoint (compared to 8.7% of patients who received placebo). In the second study, 76.5% of patients who received [the combination] achieved this endpoint (compared to 10.5% of patients who received placebo).”

The FDA noted that elagolix, estradiol, and norethindrone capsules carries a Boxed Warning regarding risks of vascular events and thrombotic or thromboembolic disorders in women taking the combination, and warned that women who experience a blood clot, heart attack, or stroke should immediately halt treatment. For this reason, combination elagolix, estradiol, and norethindrone is contraindicated “in women with a history of or current blood clots and in women at increased risk for blood clots, including women over 35 years of age who smoke or women with uncontrolled hypertension,” the FDA wrote. “Other contraindications include known osteoporosis, a history of or current breast cancer or other hormonally-sensitive cancer, liver disease or undiagnosed abnormal uterine bleeding.”

The agency added that the combination may cause bone loss over time that may not fully recover upon stopping treatment. “Because bone loss may increase the risk for fractures, women should not take [the combination] for more than 24 months. Health care professionals may recommend a bone density scan (called DXA scan) when starting women on [the combination] and periodically while on treatment,” the agency wrote.

The FDA also noted that, while the combination does not prevent pregnancy, it may delay pregnancy detection due to changes in menstrual bleeding patterns. The combination may also increase blood pressure, which the agency noted should be monitored in women with controlled hypertension.

“Patients should be advised on signs and symptoms of liver injury,” the agency wrote. “Patients are advised to seek medical attention if they experience suicidal ideation or behavior, new onset or worsening depression, anxiety or other mood changes. Patients taking [the combination] may experience hair loss (alopecia). There is a risk of allergic reaction with [the combination] because its inactive ingredient, FD&C Yellow No. 5 (tartrazine) may cause allergic-type reactions (including bronchial asthma) in some women.”

Due to these and other, more common side effects — hot flushes, headache, fatigue, and irregular vaginal bleeding — combination elagolix, estradiol, and norethindrone must be dispensed with a patient Medication Guide laying out the drug’s uses and risks.

Oriahnn is manufactured by AbbVie Inc.

John McKenna, Associate Editor, BreakingMED™

Cat ID: 133

Topic ID: 83,133,730,133,192,725