Estradiol And Progesterone
FDA Drug Information • Also known as: Bijuva
- Brand Names
- Bijuva
- Dosage Form
- CAPSULE
- Product Type
- DRUG FOR FURTHER PROCESSING
Description
11 DESCRIPTION BIJUVA (estradiol and progesterone) is an oval shaped opaque capsule in which the estradiol is solubilized and the progesterone is micronized and suspended in the mixture of medium chain mono and di-glycerides and lauroyl polyoxyl-32 glycerides. Each 0.5 mg/100 mg capsule is light pink on one side, dark pink on the other side, and printed with "5C1" in white ink. Each 1 mg/100 mg capsule is light pink on one side, dark pink on the other side, and printed with "1C1" in white ink. Estradiol (estra-1,3,5 (10)-triene-3,17β-diol), an estrogen, has a molecular weight of 272.38, and chemical formula C 18 H 24 O 2 . Progesterone (pregn-4-ene-3, 20-dione) has a molecular weight of 314.47, and chemical formula C 21 H 30 O 2 . The structural formulas are as follows: Estradiol Progesterone Each BIJUVA (estradiol and progesterone) capsule contains the following inactive ingredients: ammonium hydroxide, ethanol, ethyl acetate, FD&C Red #40, gelatin, glycerin, hydrolyzed gelatin, isopropyl alcohol, lauroyl polyoxyl-32 glycerides, lecithin, medium chain mono and di- glycerides, medium chain triglycerides, polyethylene glycol, polyvinyl acetate phthalate, propylene glycol, purified water, and titanium dioxide. Chemical Structure Chemical Structure
What Is Estradiol And Progesterone Used For?
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)
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions (5.1) ]. Malignant Neoplasms [see Boxed Warning, Warnings and Precautions (5.2) ]. The most common adverse reactions with BIJUVA (incidence ≥ 3% of women and greater than placebo) are: breast tenderness, headache, nausea, vaginal bleeding, vaginal discharge and pelvic pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharmaat 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of estradiol and progesterone capsules was assessed in a 1-year trial that included 1,835 postmenopausal women (1,684 were treated with estradiol and progesterone capsules once daily and 151 women received placebo). Most women (~70%) in the active treatment groups were treated for ≥ 326 days. Treatment related adverse reactions with an incidence of ≥ 3% in either BIJUVA (estradiol and progesterone) capsules group and numerically greater than those reported in the placebo group are listed in Table 1. Table 1: Treatment-Emergent Adverse Reactions Reported at a Frequency of ≥ 3% and Numerically More Common in Women Receiving BIJUVA (estradiol and progesterone) 1 mg/100 mg Preferred Term BIJUVA 0.5 mg/100 mg BIJUVA 1 mg/100 mg Placebo (N=151) (N=424) (N=415) Breast tenderness 17 (4.0) 43 (10.4) 1 (0.7) Headache 17 (4.0) 14 (3.4) 1 (0.7) Nausea 15 (3.5) 9 (2.2) 1 (0.7) Vaginal bleeding 10 (2.4) 14 (3.4) 0 Vaginal discharge 8 (1.9) 14 (3.4) 1 (0.7) Pelvic pain 12 (2.8) 13 (3.1) 0 6.2 Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of BIJUVA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal disorders Abdominal pain and discomfort, abdominal distention, diarrhea, nausea, vomiting. General disorders and administration site conditions Fatigue, feeling abnormal, malaise. Investigations Weight increased. Metabolism and nutrition disorders Fluid retention. Musculoskeletal and connective tissue disorders Muscle spasms, pain in extremity. Nervous system disorders Dizziness, headache, somnolence. Psychiatric disorders Insomnia, sleep disorder. Reproductive system and breast disorders Breast pain, breast tenderness, uterine bleeding. Skin and subcutaneous tissue disorders Night sweats, pruritus. Vascular disorders Hot flush.
Drug Interactions
7 DRUG INTERACTIONS In-vitro and in-vivo studies have shown that estrogens and progestins are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen and progestin drug metabolism. Inducers of CYP3A4 such as St. John's wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens and progestins, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice, may increase plasma concentrations of the estrogen or the progestin or both and may result in adverse reactions. Inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. ( 7 )
Contraindications
4 CONTRAINDICATIONS BIJUVA is contraindicated in women with any of the following conditions: Abnormal genital bleeding of unknown etiology [see Warnings and Precautions (5.2) ]. Breast cancer or a history of breast cancer [see Warnings and Precautions (5.2) ]. Estrogen-dependent neoplasia [see Warnings and Precautions (5.2) ]. Active deep vein thrombosis (DVT), pulmonary embolisum (PE), or history of these conditions [see Warnings and Precautions (5.1) ]. Active arterial thromboembolic disease (for example, stroke, myocardial infarction (MI)), or a history of these conditions [see Warnings and Precautions (5.1) ]. Known anaphylactic reaction, angioedema, or hypersensitivity to BIJUVA. Hepatic impairment or disease [see Warnings and Precautions (5.8) ] Known thrombophilic disorders, such as protein C, protein S, or antithrombin deficiency Undiagnosed abnormal genital bleeding ( 4 , 5.2 ) Breast cancer or a history of breast cancer ( 4 , 5.2 ) Estrogen-dependent neoplasia ( 4 , 5.2 ) Active DVT, PE, or history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions ( 4 , 5.1 ) Known anaphylactic reaction, angioedema, or hypersensitivity to BIJUVA ( 4 , 5.15 ) Hepatic impairment or disease ( 4 , 5.8 ) Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary BIJUVA is not indicated for use in pregnancy. There are no data with the use of BIJUVA in pregnant women, however, epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Overdosage
10 OVERDOSAGE Overdosage of estrogen plus progestogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of BIJUVA therapy with institution of appropriate symptomatic care.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied BIJUVA (estradiol and progesterone) capsules, 0.5 mg/100 mg, are oval-shaped opaque capsules, which are light pink on one side and dark pink on the other side. Each capsule is imprinted in white ink indicating the dosage strength (5C1). BIJUVA (estradiol and progesterone) capsules, 0.5 mg/100 mg, are provided in a blister package of 30 capsules. BIJUVA (estradiol and progesterone) capsules, 1 mg/100 mg, are oval-shaped opaque capsules, which are light pink on one side and dark pink on the other side. Each capsule is imprinted in white ink indicating the dosage strength (1C1). BIJUVA (estradiol and progesterone) capsules, 1 mg/100 mg, are provided in a blister package of 30 capsules. BIJUVA (estradiol and progesterone) capsules, 0.5 mg/100 mg NDC 68308-751-30 BIJUVA (estradiol and progesterone) capsules, 1 mg/100 mg NDC 68308-750-30 Keep out of reach of children. Packages are not child-resistant. 16.2 Storage and Handling Store at 20°C to 25ºC (68°F to 77ºF), excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). [See USP Controlled Room Temperature]
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.