Bijuva 1-100mg 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
Not applicable (Contraindicated)
FDA Approved
Oct 2018
DEA Schedule
Not Controlled
Overview
What is this medicine?
Bijuva is a medication that contains two female hormones, estradiol (an estrogen) and progesterone (a progestin). It is used to help relieve moderate to severe hot flashes and night sweats that can happen during menopause. The progesterone is included to protect the lining of the uterus from changes that can occur when taking estrogen alone.
How to Use This Medicine
Taking Your Medication
To get the most benefit from this drug, take it exactly as directed by your doctor. Carefully read all the information provided with your medication and follow the instructions closely.
Take this medication in the evening, with food, as this can help your body absorb the drug more effectively.
Continue taking this medication as prescribed by your doctor or healthcare provider, even if you start feeling well. 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, avoiding bathrooms and areas prone to moisture.
Keep all medications in a secure location, out of the reach of children and pets, to prevent accidental ingestion or exposure.
Dispose of unused or expired medications responsibly. 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 methods or explore local drug take-back programs.
Missing 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 this drug, take it exactly as directed by your doctor. Carefully read all the information provided with your medication and follow the instructions closely.
Take this medication in the evening, with food, as this can help your body absorb the drug more effectively.
Continue taking this medication as prescribed by your doctor or healthcare provider, even if you start feeling well. 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, avoiding bathrooms and areas prone to moisture.
Keep all medications in a secure location, out of the reach of children and pets, to prevent accidental ingestion or exposure.
Dispose of unused or expired medications responsibly. 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 methods or explore local drug take-back programs.
Missing 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
- Maintain a healthy lifestyle, including a balanced diet and regular exercise.
- Avoid smoking, as it increases the risk of serious cardiovascular side effects.
- 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:
1 capsule (estradiol 1 mg/progesterone 100 mg) orally once daily in the evening
Dose Range:
1 - 1 mg
Condition-Specific Dosing:
vasomotor_symptoms_menopause:
1 capsule (estradiol 1 mg/progesterone 100 mg) orally once daily in the evening
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, use with caution.
Moderate:
No specific dose adjustment recommended, use with caution.
Severe:
Use with caution; monitor for adverse effects. Not specifically studied.
Dialysis:
Not available; use with caution.
Hepatic Impairment:
Mild:
Use with caution; monitor for adverse effects.
Moderate:
Use with caution; monitor for adverse effects.
Severe:
Contraindicated in severe hepatic dysfunction or disease.
Pharmacology
Mechanism of Action
Estradiol is an estrogen receptor agonist, binding to and activating estrogen receptors (ERΞ± and ERΞ²) in target tissues to produce estrogenic effects. Progesterone is a progestin, binding to and activating progesterone receptors (PR) in target tissues. In combination HRT, progesterone is added to reduce the risk of endometrial hyperplasia and cancer associated with unopposed estrogen therapy in women with an intact uterus.
Pharmacokinetics
Absorption:
Bioavailability:
Not precisely quantified for oral combination, but both components are well absorbed.
Tmax:
Estradiol: ~5-8 hours; Progesterone: ~2-6 hours
FoodEffect:
Food increases the absorption of both estradiol and progesterone, leading to higher Cmax and AUC.
Distribution:
Vd:
Estradiol: ~1 L/kg; Progesterone: ~2-4 L/kg
ProteinBinding:
Estradiol: >95% (primarily to sex hormone-binding globulin [SHBG] and albumin); Progesterone: 96-99% (primarily to albumin and corticosteroid-binding globulin [CBG])
CnssPenetration:
Limited (both cross the blood-brain barrier to some extent)
Elimination:
HalfLife:
Estradiol: ~13-17 hours; Progesterone: ~5-20 hours
Clearance:
Not precisely quantified for oral combination.
ExcretionRoute:
Primarily renal (as glucuronide and sulfate conjugates for estradiol metabolites; as pregnanediol glucuronide for progesterone metabolites).
Unchanged:
<1% (both)
Pharmacodynamics
OnsetOfAction:
Clinical effects (e.g., reduction in hot flashes) typically observed within weeks.
PeakEffect:
Not precisely defined for therapeutic effect; related to steady-state concentrations.
DurationOfAction:
Daily dosing maintains therapeutic levels.
Safety & Warnings
BLACK BOX WARNING
Estrogen-alone therapy and estrogen plus progestin therapy 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 (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [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 CE (0.625 mg) plus MPA (2.5 mg) relative to placebo. Estrogen-alone therapy increases the risk of endometrial cancer in a woman with a uterus. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which can be a precursor to endometrial cancer.
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 or seek immediate 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, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes.
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or severe upset stomach or vomiting.
Signs of high blood pressure: severe headache or dizziness, passing out, or changes in eyesight.
Signs of low calcium levels: muscle cramps or spasms, numbness and tingling, or seizures.
Weakness on one side of the body, trouble speaking or thinking, changes in balance, drooping on one side of the face, or blurred eyesight.
Eyesight changes or loss, bulging eyes, or changes in how contact lenses feel.
A lump in the breast, breast pain or soreness, or nipple discharge.
Vaginal bleeding.
Vaginal itching or discharge.
Pelvic pain.
Memory problems or loss.
Feeling very tired or weak.
Swelling or fluid retention in the body (tell your doctor if you experience swelling, weight gain, or trouble breathing).
Blood Clots and High Calcium Levels
If you experience any of the following symptoms, seek medical help immediately:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, changes in color, or pain in a leg or arm; or trouble speaking or swallowing.
Signs of high calcium levels (more common in people with cancer): weakness, confusion, feeling tired, headache, upset stomach or vomiting, constipation, or bone pain.
Other Possible Side Effects
Like all medications, this drug may cause side effects in some people. While many individuals may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Tender breasts.
Headache.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact 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 or seek immediate 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, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes.
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or severe upset stomach or vomiting.
Signs of high blood pressure: severe headache or dizziness, passing out, or changes in eyesight.
Signs of low calcium levels: muscle cramps or spasms, numbness and tingling, or seizures.
Weakness on one side of the body, trouble speaking or thinking, changes in balance, drooping on one side of the face, or blurred eyesight.
Eyesight changes or loss, bulging eyes, or changes in how contact lenses feel.
A lump in the breast, breast pain or soreness, or nipple discharge.
Vaginal bleeding.
Vaginal itching or discharge.
Pelvic pain.
Memory problems or loss.
Feeling very tired or weak.
Swelling or fluid retention in the body (tell your doctor if you experience swelling, weight gain, or trouble breathing).
Blood Clots and High Calcium Levels
If you experience any of the following symptoms, seek medical help immediately:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, changes in color, or pain in a leg or arm; or trouble speaking or swallowing.
Signs of high calcium levels (more common in people with cancer): weakness, confusion, feeling tired, headache, upset stomach or vomiting, constipation, or bone pain.
Other Possible Side Effects
Like all medications, this drug may cause side effects in some people. While many individuals may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Tender breasts.
Headache.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact 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., partial or complete loss of vision)
- Numbness or weakness in an arm or leg, especially on one side of the body
- Speech problems
- Leg pain, swelling, or tenderness (especially in the calf)
- Yellowing of the skin or eyes (jaundice)
- New breast lump or changes in existing breast lumps
- Unusual vaginal bleeding (any bleeding after menopause or changes in bleeding pattern)
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. Do not take this medication if you are pregnant.
Additionally, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Natural products and vitamins you are using
Any existing health problems
This information is crucial to ensure your safety while taking this medication. Always consult with your doctor before starting, stopping, or changing the dosage of any medication to verify that it is safe for you to take this medication with your other medications and health conditions.
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. Do not take this medication if you are pregnant.
Additionally, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Natural products and vitamins you are using
Any existing health problems
This information is crucial to ensure your safety while taking this medication. Always consult with your doctor before starting, stopping, or changing the dosage of any medication to verify that it is safe for you to take this medication with your other medications and health conditions.
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 undergoing certain surgical procedures. If you need to stop taking this medication, your doctor will provide guidance on when to resume taking it after your surgery or procedure.
If you anticipate being immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor. Prolonged immobility may increase your risk of developing blood clots. If you have diabetes, 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 lead to elevated triglyceride levels. If you have a history of high triglyceride levels, inform your doctor.
Adhere to your doctor's recommendations for regular blood work and other laboratory tests. It is also essential to maintain a schedule of regular breast exams and gynecology check-ups, as well as perform breast self-exams as instructed by your doctor.
The risk of certain side effects, such as heart attack, stroke, breast cancer, and ovarian cancer, may vary depending on factors like the duration of estrogen therapy, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor to understand your specific situation.
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.
Smoking can increase your risk of heart disease, so it is recommended that you do not smoke. Talk to your doctor about quitting smoking. It is also advisable to limit your alcohol consumption.
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 immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor. Prolonged immobility may increase your risk of developing blood clots. If you have diabetes, 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 lead to elevated triglyceride levels. If you have a history of high triglyceride levels, inform your doctor.
Adhere to your doctor's recommendations for regular blood work and other laboratory tests. It is also essential to maintain a schedule of regular breast exams and gynecology check-ups, as well as perform breast self-exams as instructed by your doctor.
The risk of certain side effects, such as heart attack, stroke, breast cancer, and ovarian cancer, may vary depending on factors like the duration of estrogen therapy, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor to understand your specific situation.
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.
Smoking can increase your risk of heart disease, so it is recommended that you do not smoke. Talk to your doctor about quitting smoking. It is also advisable to limit your alcohol consumption.
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:
Seek immediate medical attention or call a poison control center (e.g., 1-800-222-1222). Treatment is generally supportive; there is no specific antidote.
Drug Interactions
Contraindicated Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane)
- Tamoxifen
- Fulvestrant
Major Interactions
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's Wort): May decrease estrogen/progestin levels, reducing efficacy.
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): May increase estrogen/progestin levels, increasing risk of adverse effects.
- Thyroid hormone replacement (e.g., levothyroxine): Estrogens can increase thyroid-binding globulin (TBG), potentially increasing thyroid hormone requirements.
Moderate Interactions
- Anticoagulants (e.g., warfarin): Estrogens may alter the effects of anticoagulants; monitor INR.
- Corticosteroids: Estrogens may decrease the clearance of corticosteroids, leading to increased effects.
- Cyclosporine: Estrogens may inhibit cyclosporine metabolism, increasing its levels and toxicity.
- Lamotrigine: Estrogens may decrease lamotrigine levels, potentially leading to loss of seizure control.
Minor Interactions
- Fluvoxamine (CYP1A2 inhibitor): May slightly increase estradiol levels.
- Smoking: May decrease estrogen levels and increase cardiovascular risk.
Monitoring
Baseline Monitoring
Complete medical history and physical examination (including blood pressure, breast exam, pelvic exam)
Rationale: To identify contraindications, risk factors, and establish baseline health status.
Timing: Prior to initiation of therapy.
Mammography
Rationale: To screen for breast cancer before initiating HRT.
Timing: Prior to initiation of therapy, as appropriate for age and risk factors.
Lipid profile
Rationale: To assess cardiovascular risk factors.
Timing: Prior to initiation of therapy.
Liver function tests (LFTs)
Rationale: To assess hepatic function, especially given hepatic metabolism.
Timing: Prior to initiation of therapy, if clinically indicated.
Routine Monitoring
Annual physical examination (including blood pressure, breast exam, pelvic exam)
Frequency: Annually
Target: Normal for age and health status
Action Threshold: Any significant change or abnormality requires further investigation.
Mammography
Frequency: Periodically, as recommended by guidelines (e.g., annually or biennially)
Target: No suspicious findings
Action Threshold: New lumps, pain, discharge, or suspicious imaging findings require immediate investigation.
Lipid profile
Frequency: Periodically, as clinically indicated (e.g., every 1-3 years)
Target: Optimal levels for cardiovascular health
Action Threshold: Significant worsening of lipid profile may warrant re-evaluation of HRT or additional interventions.
Liver function tests (LFTs)
Frequency: Periodically, if clinically indicated or if symptoms of hepatic dysfunction develop.
Target: Within normal limits
Action Threshold: Elevated LFTs require investigation and potential discontinuation.
Symptom Monitoring
- Signs and symptoms of venous thromboembolism (e.g., leg pain/swelling, chest pain, shortness of breath)
- Signs and symptoms of stroke (e.g., sudden severe headache, vision changes, weakness/numbness on one side of body, speech difficulty)
- Signs and symptoms of myocardial infarction (e.g., chest pain, arm pain, shortness of breath, sweating)
- Abnormal vaginal bleeding (any new or persistent bleeding)
- Breast lumps or changes
- Jaundice or other signs of liver problems
- Severe headaches or migraines
- Changes in vision
- Mood disturbances or depression
Special Patient Groups
Pregnancy
Contraindicated. Bijuva is not indicated for use in pregnant women. There is no indication for estrogen or progestin therapy during pregnancy, and there is evidence of fetal harm with estrogen exposure during pregnancy.
Trimester-Specific Risks:
First Trimester:
Potential for adverse effects on fetal development, including genital abnormalities.
Second Trimester:
Not applicable; contraindicated.
Third Trimester:
Not applicable; contraindicated.
Lactation
Not recommended. Estrogens and progestins are excreted in human milk and may decrease the quantity and quality of breast milk. Potential adverse effects on the nursing infant are unknown but possible.
Infant Risk:
Moderate risk (L3); potential for adverse effects on infant (e.g., feminization, decreased milk supply). Weigh benefits vs. risks.
Pediatric Use
Not indicated for use in pediatric patients. Safety and effectiveness have not been established.
Geriatric Use
Use with caution. Women 65 years of age or older have an increased risk of probable dementia with estrogen plus progestin therapy. Use 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 hormone therapy combining estradiol and progesterone in a single oral capsule.
- It is specifically indicated for moderate to severe vasomotor symptoms due to menopause in women with a uterus.
- Patients should be advised of the Black Box Warnings regarding cardiovascular events, breast cancer, endometrial cancer, and probable dementia.
- Therapy should be individualized, using the lowest effective dose for the shortest duration consistent with treatment goals and risks.
- Regular follow-up and monitoring, including breast exams and mammograms, are crucial.
- Food significantly increases the absorption of both components; consistent administration with or without food should be maintained, but the label recommends taking it in the evening.
Alternative Therapies
- Selective Serotonin Reuptake Inhibitors (SSRIs) / Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) (e.g., paroxetine, venlafaxine) for vasomotor symptoms.
- Gabapentin for vasomotor symptoms.
- Clonidine for vasomotor symptoms.
- Non-hormonal therapies and lifestyle modifications (e.g., diet, exercise, stress reduction, avoiding triggers).
Cost & Coverage
Average Cost:
$150 - $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's 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 be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.