Bijuva

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE BIJUVA is a combination of an estrogen and progesterone indicated in a woman with a uterus for the treatment of moderate to severe vasomotor symptoms due to menopause. ( 1.1 ) 1.1 Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause Dosage and administration 2 DOSAGE AND ADMINISTRATION The timing of BIJUVA initiation can affect the overall risk-benefit profile. Consider initiating BIJUVA in women < 60 years old or < 10 years from onset of menopause [see Warnings and Precautions (5) , Adverse Reactions (6.1) , Use in Specific Populations (8.5) and Clinical Studies (14) ] . Take a single BIJUVA capsule orally each evening with food. Generally, start therapy with BIJUVA 0.5 mg estradiol/100 mg progesterone dosage strength. Make dosage adjustment based on the clinical response. Attempt to taper or discontinue BIJUVA at 3 to 6 month intervals. One capsule orally each evening with food. (2.1) Warnings and cautions 5 WARNINGS AND PRECAUTIONS Cardiovascular Disorders: Increased risks of PE, DVT, stroke, and MI are reported with estrogen plus progestin therapy. Manage risk factors for arterial vascular disease and/or venous thromboembolisum. Discontinue if an arterial or venous thrombotic or thromboembolic event occurs. ( 5.1 ) Malignant Neoplasms: Assess risk and provide surveillance measures for breast cancer, such as breast examinations and mammography. ( 5.2 ) Estrogens increase the risk of gallbladder disease. ( 5.3 ) Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia, or cholestatic jaundice occurs. ( 5.4 , 5.5 , 5.7 , 5.8 ) Monitor thyroid function in women on thyroid replacement hormone therapy. ( 5.9 , 5.15 ) 5.1 Cardiovascular Disorders BIJUVA is contraindicated in females with active DVT, PE, arterial thromboembolic disease (e.g., stroke, MI) disease, or a history of these conditions [see Contraindications (4) ] . Immediately discontinue BIJUVA if a PE, DVT, stroke, or MI occurs or is suspected. If feasible, discontinue BIJUVA at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. The safety and efficacy of BIJUVA for the prevention of cardiovascular disorders has not been established [see Clinical Studies (14.4) ] . The Women's Health Initiative (WHI) estrogen plus progestin trial reported increased risks of PE, DVT, stroke, and MI in postmenopausal women (50 to 79 years of age, average age 63.4 years) during the 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo. Analyses were also conducted in women aged 50-59 years, a group of women more likely to present with new onset of moderate to severe VMS compared to women in other age groups in the trial [see Clinical Studies (14.4) ] . Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin trial of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Venous Thromboembolism In women aged 50-59 years, the WHI estrogen plus progestin trial reported a relative risk for PE of 2.05 (95% confidence interval [CI], 0.89-4.71) for CE/MPA compared to placebo, with a risk difference of 6 per 10,000 women-years (WYs; 11 versus 5). The relative risk for DVT was 3.01 (95% CI, 1.36-6.66) in those receiving CE/MPA compared to placebo, with a risk difference of 10 per 10,000 WYs (15 versus 5) [see Clinical Studies (14.4) ] . In the overall study population of women aged 50-79 years (average 63.4 years), the trial reported a relative risk for PE of 1.98 (95% CI, 1.36-2.87) for CE/MPA compared to placebo, with a risk difference of 9 per 10,000 WYs (18 versus 9). The relative risk for DVT was 1.87 (95% CI, 1.37-2.54) for CE/MPA compared to placebo, with a risk difference of 12 per 10,000 WYs (25 versus 14) [see Clinical Studies (14.4) ] . Stroke In women aged 50-59 years, the WHI estrogen plus progestin trial reported a relative risk for stroke of 1.51 (95% CI, 0.81-2.82) for CE/MPA compared to placebo, with a risk difference of 5 per 10,000 WYs (15 versus 10) [see Clinical Studies (14.4) ] . In the overall study population of women aged 50-79 years (average 63.4 years), the WHI estrogen plus progestin trial reported relative risk for stroke of 1.37 (95% CI, 1.07-1.76) for CE/MPA compared to placebo, with a risk difference of 9 per 10,000 WYs (33 versus 24) [see Clinical Studies (14.4) ] . Coronary Heart Disease In women 50 to 59 years of age, the WHI estrogen plus progestin trial reported a relative risk for coronary heart disease (CHD) events (defined as nonfa