Bijuva From TherapeuticsMD

Pharmacy Times, April 2022, Volume 88, Issue 4

TherapeuticsMD, Inc has submitted a supplemental New Drug Application for estradiol and progesterone capsules 0.5 mg/100 mg (Bijuva) to the FDA.

TherapeuticsMD, Inc has submitted a supplemental New Drug Application for estradiol and progesterone capsules 0.5 mg/100 mg (Bijuva) to the FDA.1

The FDA approved Bijuva capsules consisting of 1 mg estradiol and 100 mg progesterone in 2018 for the treatment of moderate to severe vasomotor symptoms, also known as hot flashes, related to menopause in women with a uterus.2 The medication is a combination hormone therapy of bioidentical estradiol and bio-identical progesterone.1

Pharmacology and Pharmacokinetics

Estrogens affect the release and reduce the levels of follicle-stimulating hormone, gonadotropins, and luteinizing hormone in postmenopausal women. Progesterone enhances cellular differentiation and opposes the actions of estrogens by increasing the local metabolism of estrogens to less active metabolites, inducing gene products that reduce the cellular responses to estrogen, or reducing estrogen receptor levels. The time to maximum concentration is approximately 5 hours for estradiol and 3 hours for progesterone. Bijuva reaches steady-state plasma concentration within
7 days of oral administration. The half-life of estradiol is approximately 26 hours, and the half-life of progesterone is approximately 10 hours.2

Dosage and Administration

The dose of Bijuva is 1 capsule orally each evening with food.2

Clinical Trials

The effectiveness and safety of Bijuva 1 mg/100 mg on moderate to severe asomotor symptoms related to menopause were evaluated in a 12-week, double-blind, placebo-controlled, randomized substudy of a 52-week safety study. A total of 726 postmenopausal women were randomized to receive estradiol and progesterone in multiple dose combinations or a placebo. The coprimary efficacy end points included the mean weekly reduction in frequency and severity of moderate to severe vasomotor symptoms at weeks 4 and 12, with a clinically meaningful reduction threshold in frequency of vasomotor symptoms. Bijuva 1 mg/100 mg was found to reduce the frequency and severity of moderate to severe vasomotor symptoms from baseline compared with the placebo at weeks 4 and 12 but did not demonstrate a clinically meaningful reduction threshold until week 5. The safety of Bijuva 1 mg/100 mg was assessed by the incidence of endometrial hyperplasia and malignancy within up to 52 weeks of treatment. The study found 1 case of endometrial hyperplasia and no cases of endometrial cancer in the Bijuva 1 mg/100 mg group, and no cases of hyperplasia or endometrial cancer in the placebo group.2

Contraindictions, Warnings, and Precautions

Bijuva carries a boxed warning stating that estrogen alone and estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis (DVT), invasive breast cancer, myocardial infarction (MI), pulmonary embolism (PE), and stroke. The WHI estrogen-alone substudy reported increased risks of DVT and stroke. Two ancillary studies of the WHI Memory Study reported an increased risk of probable dementia in postmenopausal women 65 years and older with either estrogen-alone or estrogen plus progestin therapy. The boxed warning also states that there is an increased risk of endometrial cancer in patients with a uterus who use unopposed estrogens.

Treatment with Bijuva is contraindicated in women with active arterial thromboembolic disease, such as MI and stroke, or a history of these conditions; active DVT, PE, or a history of these conditions; anaphylaxis, angioedema, or hypersensitivity to the medication; antithrombin, protein C, or protein S deficiency, or other known thrombophilic disorders; breast cancer or a history of breast cancer; estrogen-dependent neoplasia; hepatic disease or impairment; or undiagnosed abnormal genital bleeding.

The use of estrogens increases the risk of gallbladder disease. Treatment with estrogen should be discontinued if cholestatic jaundice, loss of vision, severe hypercalcemia, or severe hypertriglyceridemia occurs. Women using thyroid replacement hormone therapy concurrently with Bijuva should have their thyroid function monitored. Concomitant use of Bijuva with inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism and alter the estrogen plasma concentration.

The most common adverse reactions are breast tenderness, headaches, pelvic pain, vaginal bleeding, and vaginal discharge.2

Monica Holmberg, PharmD, BCPS, is a pharmacist and Pharmacy Times® contributor.

Reference

1. TherapeuticsMD announces submission o flow dose Bijuva 0.5mg/100 mg supplemental new drug application to FDA. TherapeuticsMD, Inc. News release. May 25, 2021. Accessed March 4,2022. https://ir.therapeuticsmd.com/news-releases/news-release-details/therapeuticsmd-announces-submission-low-dose-bijuvar-05-mg100-mg

2. Bijuva. Prescribing information. TherapeuticsMD, Inc. 2021. Accessed March 4, 2022. https://www.bijuva.com/pi.pdf