Bijuva 0.5mg/100mg Capsules
WARNING: Do not use this drug to prevent heart disease or dementia. A study of women taking an estrogen with a progestin showed a raised chance of heart attack, stroke, blood clot, breast cancer, and dementia. The chance of stroke, blood clot, and dementia was also raised when the estrogen was taken alone. Not all products and doses were studied. It is not known if the same effects may happen with this drug.The chance of endometrial cancer may be raised with the use of estrogen alone in patients with a uterus. Use of a progestin along with estrogen may lower the risk. Call your doctor right away if you have unexplained or long-lasting vaginal bleeding.Use this drug for the shortest time needed at the lowest useful dose. Your doctor will talk with you on a regular basis to see if you need to keep taking this drug. @ COMMON USES: It is used to treat signs caused by menopause.
Drug Class
Hormone Replacement Therapy (HRT)
Pharmacologic Class
Estrogen and Progestin Combination
Pregnancy Category
X
FDA Approved
Oct 2018
DEA Schedule
Not Controlled
Overview
What is this medicine?
Bijuva is a medication that contains two female hormones, estrogen (estradiol) and progesterone. It is used to help relieve moderate to severe hot flashes (vasomotor symptoms) that some women experience during menopause. The progesterone helps protect the lining of the uterus from overgrowth that can occur with estrogen alone.
How to Use This Medicine
Taking Your Medication
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription and follow the instructions closely.
Take your medication in the evening, with food, as this can help your body absorb the drug more effectively.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better. It's essential to complete the full course of treatment to ensure the best possible outcome.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication:
Store it at room temperature in a dry place, away from the bathroom.
Keep all medications in a secure location, out of the reach of children and pets, to prevent accidental ingestion or misuse.
Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so by your pharmacist or healthcare provider. Instead, check with your pharmacist for guidance on the best disposal method or explore local drug take-back programs.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's almost time for your next scheduled dose (less than 2 hours away), skip the missed dose and resume your regular dosing schedule. Remember:
Do not take two doses at the same time.
* Avoid taking extra doses, as this can increase the risk of side effects.
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription and follow the instructions closely.
Take your medication in the evening, with food, as this can help your body absorb the drug more effectively.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better. It's essential to complete the full course of treatment to ensure the best possible outcome.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication:
Store it at room temperature in a dry place, away from the bathroom.
Keep all medications in a secure location, out of the reach of children and pets, to prevent accidental ingestion or misuse.
Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so by your pharmacist or healthcare provider. Instead, check with your pharmacist for guidance on the best disposal method or explore local drug take-back programs.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's almost time for your next scheduled dose (less than 2 hours away), skip the missed dose and resume your regular dosing schedule. Remember:
Do not take two doses at the same time.
* Avoid taking extra doses, as this can increase the risk of side effects.
Lifestyle & Tips
- Do not smoke, as smoking increases the risk of blood clots, stroke, and heart attack, especially when taking hormones.
- Maintain a healthy diet and engage in regular physical activity.
- Discuss any new or worsening symptoms with your doctor promptly.
- Attend all scheduled follow-up appointments and screenings (e.g., mammograms).
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
One capsule (estradiol 0.5 mg/progesterone 100 mg) orally once daily in the evening with food.
Dose Range:
0.5 - 100 mg
Condition-Specific Dosing:
vasomotorSymptoms:
One capsule (estradiol 0.5 mg/progesterone 100 mg) orally once daily in the evening with food.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific dosage adjustment recommended.
Moderate:
No specific dosage adjustment recommended.
Severe:
Not studied; use with caution.
Dialysis:
Not studied; use with caution.
Hepatic Impairment:
Mild:
Use with caution; monitor for adverse effects.
Moderate:
Not recommended.
Severe:
Contraindicated.
Pharmacology
Mechanism of Action
Estradiol is an estrogen that acts by binding to estrogen receptors (ERΞ± and ERΞ²) in target tissues, forming a complex that interacts with DNA to regulate gene expression. This leads to the physiological effects of estrogen, including the reduction of vasomotor symptoms associated with menopause. Progesterone is a progestin that acts by binding to progesterone receptors (PR) in target tissues. In estrogen-primed endometrial tissue, progesterone induces secretory changes and prevents endometrial hyperplasia, which is a risk associated with unopposed estrogen therapy.
Pharmacokinetics
Absorption:
Bioavailability:
Estradiol: Approximately 5% (due to significant first-pass metabolism); Progesterone: Approximately 10% (due to significant first-pass metabolism)
Tmax:
Estradiol: 4-6 hours; Progesterone: 2-5 hours
FoodEffect:
Administration with food increases the bioavailability of both estradiol and progesterone, and reduces inter-subject variability.
Distribution:
Vd:
Estradiol: 18 L/kg; Progesterone: 2000 L
ProteinBinding:
Estradiol: Approximately 98% (primarily to sex hormone-binding globulin [SHBG] and albumin); Progesterone: Approximately 96-99% (primarily to albumin and corticosteroid-binding globulin [CBG])
CnssPenetration:
Yes (both estradiol and progesterone cross the blood-brain barrier)
Elimination:
HalfLife:
Estradiol: 13-17 hours; Progesterone: 16-18 hours
Clearance:
Not available
ExcretionRoute:
Mainly renal (as glucuronide and sulfate conjugates); some biliary/fecal
Unchanged:
Less than 1% (both estradiol and progesterone)
Pharmacodynamics
OnsetOfAction:
Weeks to months for full therapeutic effect on vasomotor symptoms.
PeakEffect:
Not precisely defined for clinical effect, but steady-state concentrations are reached within days.
DurationOfAction:
Daily dosing maintains therapeutic levels.
Safety & Warnings
BLACK BOX WARNING
Estrogens and progestins should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50-79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo. The WHI Memory Study (WHIMS) reported an increased risk of probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo. These risks apply to Bijuva as it contains both estrogen and progestin.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of liver problems: dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellow skin and eyes.
Signs of gallbladder problems: pain in the upper right abdominal area, right shoulder, or between the shoulder blades, yellow skin and eyes, fever with chills, bloating, or severe stomach upset or vomiting.
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision.
Signs of low calcium levels: muscle cramps or spasms, numbness and tingling, or seizures.
Weakness on one side of the body, difficulty speaking or thinking, changes in balance, drooping on one side of the face, or blurred vision.
Changes in vision or loss of vision, bulging eyes, or changes in how contact lenses feel.
Breast lump, breast pain or tenderness, or nipple discharge.
Vaginal bleeding or discharge.
Vaginal itching.
Pelvic pain.
Memory problems or loss.
Feeling extremely tired or weak.
This medication may cause fluid retention, leading to swelling or weight gain. If you experience swelling, weight gain, or difficulty breathing, inform your doctor.
Blood Clots and High Calcium Levels
Seek immediate medical attention if you experience signs of a blood clot, such as:
Chest pain or pressure
Coughing up blood
Shortness of breath
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Difficulty speaking or swallowing
High calcium levels have been reported in some people with cancer taking medications like this one. If you experience any of the following symptoms, contact your doctor right away:
Weakness
Confusion
Fatigue
Headache
Stomach upset or vomiting
Constipation
Bone pain
Other Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild ones. If you are concerned about any side effects or if they persist, contact your doctor. Some common side effects include:
Tender breasts
* Headache
This is not an exhaustive list of possible side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of liver problems: dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellow skin and eyes.
Signs of gallbladder problems: pain in the upper right abdominal area, right shoulder, or between the shoulder blades, yellow skin and eyes, fever with chills, bloating, or severe stomach upset or vomiting.
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision.
Signs of low calcium levels: muscle cramps or spasms, numbness and tingling, or seizures.
Weakness on one side of the body, difficulty speaking or thinking, changes in balance, drooping on one side of the face, or blurred vision.
Changes in vision or loss of vision, bulging eyes, or changes in how contact lenses feel.
Breast lump, breast pain or tenderness, or nipple discharge.
Vaginal bleeding or discharge.
Vaginal itching.
Pelvic pain.
Memory problems or loss.
Feeling extremely tired or weak.
This medication may cause fluid retention, leading to swelling or weight gain. If you experience swelling, weight gain, or difficulty breathing, inform your doctor.
Blood Clots and High Calcium Levels
Seek immediate medical attention if you experience signs of a blood clot, such as:
Chest pain or pressure
Coughing up blood
Shortness of breath
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Difficulty speaking or swallowing
High calcium levels have been reported in some people with cancer taking medications like this one. If you experience any of the following symptoms, contact your doctor right away:
Weakness
Confusion
Fatigue
Headache
Stomach upset or vomiting
Constipation
Bone pain
Other Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or may only have mild ones. If you are concerned about any side effects or if they persist, contact your doctor. Some common side effects include:
Tender breasts
* Headache
This is not an exhaustive list of possible side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Sudden chest pain or shortness of breath
- Sudden severe headache or dizziness
- Sudden vision changes (e.g., blurred vision, loss of vision)
- Pain, swelling, or redness in your leg (especially the calf)
- Yellowing of your skin or eyes (jaundice)
- New breast lump or changes in your breasts
- Unusual vaginal bleeding or spotting after menopause
- Severe abdominal pain
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, including:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack
+ Stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Hysterectomy (removal of the uterus)
Pregnancy or potential pregnancy. Note: This medication is contraindicated during pregnancy. If you are pregnant, do not take this medication.
Additionally, to ensure safe treatment, it is crucial to:
Inform your doctor and pharmacist about all medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Discuss your health problems with your doctor to verify that it is safe to take this medication in conjunction with your other treatments and health conditions.
Avoid starting, stopping, or changing the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, including:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack
+ Stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Hysterectomy (removal of the uterus)
Pregnancy or potential pregnancy. Note: This medication is contraindicated during pregnancy. If you are pregnant, do not take this medication.
Additionally, to ensure safe treatment, it is crucial to:
Inform your doctor and pharmacist about all medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Discuss your health problems with your doctor to verify that it is safe to take this medication in conjunction with your other treatments and health conditions.
Avoid starting, stopping, or changing the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will provide guidance on when to resume taking it after the surgery or procedure.
If you anticipate being inactive for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as prolonged inactivity may increase your risk of developing blood clots.
If you have diabetes (high blood sugar), it is crucial to closely monitor your blood sugar levels while taking this medication.
Be aware that this medication can cause high blood pressure. Follow your doctor's instructions for regular blood pressure checks.
Additionally, this drug may cause elevated triglyceride levels. Inform your doctor if you have a history of high triglyceride levels.
Adhere to your doctor's recommendations for regular blood work and other laboratory tests to ensure your safety while taking this medication.
It is also important to maintain regular breast exams and gynecology check-ups, and to perform breast self-exams as instructed by your doctor.
The risk of certain side effects, such as heart attack, stroke, breast cancer, ovarian cancer, and others, may vary depending on individual factors, including the duration of estrogen use, whether it is taken with or without a progestin, and other factors. Discuss the benefits and risks of using this medication with your doctor.
This medication may interfere with certain laboratory tests. Inform all your healthcare providers and laboratory personnel that you are taking this drug.
If you consume grapefruit juice or eat grapefruit regularly, consult with your doctor, as this may interact with the medication.
Smoking can increase the risk of heart disease, so it is recommended that you do not smoke. Discuss any concerns with your doctor.
Limit your alcohol consumption while taking this medication.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are breastfeeding, consult with your doctor to discuss any potential risks to your baby.
If you anticipate being inactive for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as prolonged inactivity may increase your risk of developing blood clots.
If you have diabetes (high blood sugar), it is crucial to closely monitor your blood sugar levels while taking this medication.
Be aware that this medication can cause high blood pressure. Follow your doctor's instructions for regular blood pressure checks.
Additionally, this drug may cause elevated triglyceride levels. Inform your doctor if you have a history of high triglyceride levels.
Adhere to your doctor's recommendations for regular blood work and other laboratory tests to ensure your safety while taking this medication.
It is also important to maintain regular breast exams and gynecology check-ups, and to perform breast self-exams as instructed by your doctor.
The risk of certain side effects, such as heart attack, stroke, breast cancer, ovarian cancer, and others, may vary depending on individual factors, including the duration of estrogen use, whether it is taken with or without a progestin, and other factors. Discuss the benefits and risks of using this medication with your doctor.
This medication may interfere with certain laboratory tests. Inform all your healthcare providers and laboratory personnel that you are taking this drug.
If you consume grapefruit juice or eat grapefruit regularly, consult with your doctor, as this may interact with the medication.
Smoking can increase the risk of heart disease, so it is recommended that you do not smoke. Discuss any concerns with your doctor.
Limit your alcohol consumption while taking this medication.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are breastfeeding, consult with your doctor to discuss any potential risks to your baby.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Breast tenderness
- Abdominal pain
- Drowsiness/fatigue
- Withdrawal bleeding in women
What to Do:
There is no specific antidote. Treatment is symptomatic and supportive. In case of suspected overdose, contact a poison control center immediately (e.g., 1-800-222-1222 in the US) or seek emergency medical attention.
Drug Interactions
Major Interactions
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenobarbital, St. John's Wort): May decrease estrogen and progestin levels, reducing efficacy.
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): May increase estrogen and progestin levels, increasing risk of adverse effects.
- Thyroid hormone replacement therapy: Estrogens can increase thyroid-binding globulin (TBG), leading to increased circulating total thyroid hormone levels and potentially increased thyroid hormone dose requirements.
Moderate Interactions
- Corticosteroids: Estrogens may decrease the clearance of corticosteroids, leading to increased pharmacologic effects.
- Oral anticoagulants (e.g., warfarin): Estrogens may alter the effects of anticoagulants; monitor INR.
- Lamotrigine: Estrogens may decrease lamotrigine plasma concentrations, potentially leading to loss of seizure control.
Minor Interactions
- Drugs metabolized by CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4: Estrogens may inhibit these enzymes to varying degrees, potentially increasing concentrations of co-administered drugs.
Monitoring
Baseline Monitoring
Complete medical history and physical examination
Rationale: To identify contraindications, risk factors, and establish baseline health status.
Timing: Prior to initiation of therapy.
Blood pressure
Rationale: Estrogens can affect blood pressure.
Timing: Prior to initiation of therapy.
Breast examination and mammography
Rationale: To screen for breast cancer and establish baseline for future comparisons.
Timing: Prior to initiation of therapy, as appropriate for age and risk factors.
Pelvic examination and Pap test
Rationale: To screen for gynecological conditions and establish baseline.
Timing: Prior to initiation of therapy, as appropriate for age and risk factors.
Lipid profile
Rationale: Estrogens can affect lipid metabolism.
Timing: Prior to initiation of therapy.
Routine Monitoring
Annual physical examination
Frequency: Annually
Target: Normal
Action Threshold: Any significant change or new symptom.
Breast examination and mammography
Frequency: Annually or as clinically indicated
Target: Normal
Action Threshold: New lumps, pain, or suspicious findings.
Blood pressure
Frequency: Annually or more frequently if indicated
Target: <130/80 mmHg
Action Threshold: Sustained elevation (e.g., >140/90 mmHg).
Symptoms of venous thromboembolism (VTE), stroke, myocardial infarction
Frequency: Ongoing patient education and self-monitoring
Target: Absence of symptoms
Action Threshold: Any new or worsening symptoms (e.g., chest pain, shortness of breath, leg swelling, sudden severe headache, vision changes).
Symptoms of endometrial hyperplasia/cancer
Frequency: Ongoing patient education and self-monitoring
Target: Absence of symptoms
Action Threshold: Any abnormal vaginal bleeding or spotting.
Symptom Monitoring
- Unusual vaginal bleeding or spotting
- Breast lumps or changes
- Chest pain or discomfort
- Shortness of breath
- Sudden severe headache
- Dizziness or fainting
- Vision changes (e.g., sudden partial or complete loss of vision)
- Pain, swelling, or tenderness in one leg
- Yellowing of skin or eyes (jaundice)
- Severe abdominal pain
- Memory loss or cognitive decline (especially in older women)
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. There is no indication for Bijuva in pregnancy, and there is evidence of fetal harm.
Trimester-Specific Risks:
First Trimester:
Potential for adverse effects on fetal development, including genital abnormalities in female fetuses.
Second Trimester:
Not applicable, as use is contraindicated.
Third Trimester:
Not applicable, as use is contraindicated.
Lactation
Not recommended during lactation. Estrogens and progestins are excreted in human milk and may decrease milk production and quality. Potential adverse effects on the breastfed infant are unknown.
Infant Risk:
L4 (Possibly Hazardous)
Pediatric Use
Not indicated for use in pediatric patients. Safety and effectiveness have not been established.
Geriatric Use
Use with caution in women 65 years of age or older. The WHI study showed an increased risk of probable dementia in women 65 years of age or older treated with conjugated estrogens plus medroxyprogesterone acetate. Consider the lowest effective dose for the shortest duration consistent with treatment goals and risks.
Clinical Information
Clinical Pearls
- Bijuva is the first and only FDA-approved bio-identical estradiol and progesterone combination in a single oral capsule for the treatment of moderate to severe vasomotor symptoms due to menopause.
- Always take Bijuva with food in the evening to optimize absorption and reduce variability.
- Patients should be advised of the black box warnings regarding cardiovascular events, breast cancer, and dementia associated with estrogen plus progestin therapy.
- Regular follow-up and monitoring, including annual physical exams, breast exams, and mammograms, are crucial.
- Discontinue Bijuva if a thrombotic event (e.g., DVT, PE, stroke, MI) occurs or is suspected.
- Consider discontinuing or tapering Bijuva periodically (e.g., every 3-6 months) to assess the continued need for therapy and to use the lowest effective dose for the shortest duration.
- Inform patients about the importance of reporting any unusual vaginal bleeding immediately, as it may indicate endometrial pathology.
Alternative Therapies
- Other forms of HRT (e.g., transdermal patches, gels, sprays, vaginal rings, vaginal creams/tablets for local symptoms)
- Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine; fezolinetant)
- Lifestyle modifications (e.g., diet, exercise, stress reduction, avoiding triggers)
Cost & Coverage
Average Cost:
$180 - $250 per 30 capsules
Insurance Coverage:
Tier 2 or Tier 3 (Specialty/Non-Preferred Brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.