Divigel 0.75mg/day Top Gel Pk
WARNING: All products: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.Skin gel and spray:Do not let another person or a pet touch this drug or the treated part of your skin. If they do, wash their skin with soap and water. If you notice any signs that others may have been in contact with the treated area by accident, call the doctor. This may include signs of unusual sexual development like breast changes in children. @ COMMON USES: It is used to prevent or lower the signs of the change of life (menopause).It may be given to you for other reasons. Talk with the doctor.
Drug Class
Estrogen
Pharmacologic Class
Estrogen receptor agonist
Pregnancy Category
Category X
FDA Approved
Jun 2007
DEA Schedule
Not Controlled
Overview
What is this medicine?
Divigel is a gel containing the hormone estradiol, which is a form of estrogen. It's used by women after menopause to help relieve symptoms like hot flashes, night sweats, and vaginal dryness. It works by replacing the estrogen your body no longer makes.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. It's essential to use this medication as directed and follow all instructions carefully.
Application Instructions
Do not take this medication by mouth. It is for use on your skin only.
Avoid getting the medication in your mouth, nose, or eyes, as it may cause burning.
Apply the medication at the same time every day.
Wash your hands before and after applying the medication.
Apply the medication to clean, dry, healthy skin on the thigh.
Be sure to apply the medication to the correct area of the body, as specified in the package insert.
Do not apply the medication to skin with any problems or irritations.
Avoid applying the medication to the face, breast, or vagina.
Special Instructions for Certain Products
If you're using a pump, prime it before the first use, following the instructions in the package insert.
If you're using a packet, follow the instructions for application.
Do not have someone else apply the medication to your skin. If someone else must apply it, they should wear gloves and avoid touching the medication.
Precautions
Avoid exposure to fire, flames, or smoking until the medication is dry.
Let the medication dry completely before covering the treated area with clothing.
Do not wash the treated area for at least 1 hour after application.
Rotate the application site with each dose to avoid skin irritation.
Storage and Disposal
Store the medication at room temperature in a dry place, away from bathrooms.
Protect the medication from heat or open flames.
Keep all medications in a safe place, out of the reach of children and pets.
Missed Dose Instructions
If you miss a dose, apply it as soon as you remember.
If it's less than 12 hours until the next dose, skip the missed dose and return to your regular schedule.
* Do not apply two doses at the same time or use extra doses.
To use this medication correctly, follow your doctor's instructions and read all the information provided. It's essential to use this medication as directed and follow all instructions carefully.
Application Instructions
Do not take this medication by mouth. It is for use on your skin only.
Avoid getting the medication in your mouth, nose, or eyes, as it may cause burning.
Apply the medication at the same time every day.
Wash your hands before and after applying the medication.
Apply the medication to clean, dry, healthy skin on the thigh.
Be sure to apply the medication to the correct area of the body, as specified in the package insert.
Do not apply the medication to skin with any problems or irritations.
Avoid applying the medication to the face, breast, or vagina.
Special Instructions for Certain Products
If you're using a pump, prime it before the first use, following the instructions in the package insert.
If you're using a packet, follow the instructions for application.
Do not have someone else apply the medication to your skin. If someone else must apply it, they should wear gloves and avoid touching the medication.
Precautions
Avoid exposure to fire, flames, or smoking until the medication is dry.
Let the medication dry completely before covering the treated area with clothing.
Do not wash the treated area for at least 1 hour after application.
Rotate the application site with each dose to avoid skin irritation.
Storage and Disposal
Store the medication at room temperature in a dry place, away from bathrooms.
Protect the medication from heat or open flames.
Keep all medications in a safe place, out of the reach of children and pets.
Missed Dose Instructions
If you miss a dose, apply it as soon as you remember.
If it's less than 12 hours until the next dose, skip the missed dose and return to your regular schedule.
* Do not apply two doses at the same time or use extra doses.
Lifestyle & Tips
- Apply the gel to clean, dry skin on one thigh, alternating thighs daily. Do not apply to breasts or face.
- Allow the gel to dry for at least 5 minutes before dressing.
- Wash hands thoroughly after application.
- Avoid contact with eyes.
- Avoid applying to irritated or broken skin.
- Avoid smoking, as it increases the risk of blood clots and other serious side effects.
- Maintain a healthy diet and regular exercise.
- Attend all scheduled doctor's appointments and screenings (e.g., mammograms, pelvic exams).
- Discuss any concerns or side effects with your healthcare provider.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
0.75 mg Estradiol Gel applied once daily to one thigh, alternating thighs daily.
Dose Range:
0.25 - 1.25 mg
Condition-Specific Dosing:
vasomotorSymptoms:
Initial dose typically 0.25 mg or 0.5 mg daily, titrated up to 1.25 mg daily based on response. Divigel 0.75 mg/day is a specific strength.
vulvarAndVaginalAtrophy:
Typically 0.25 mg to 1.25 mg daily, lowest effective dose for shortest duration.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (not indicated for pediatric use)
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but use with caution.
Moderate:
No specific dose adjustment recommended, but use with caution.
Severe:
Use with caution; monitor for fluid retention and exacerbation of renal disease.
Dialysis:
Not available; use with caution and monitor closely.
Hepatic Impairment:
Mild:
Use with caution; monitor liver function.
Moderate:
Use with caution; monitor liver function. Estrogens are extensively metabolized by the liver.
Severe:
Contraindicated in severe liver disease due to impaired metabolism and potential for cholestasis and liver dysfunction.
Pharmacology
Mechanism of Action
Estradiol is the primary estrogen produced by the human ovary. It binds to estrogen receptors (ERΞ± and ERΞ²) in target tissues, forming a complex that interacts with DNA to regulate gene expression. This leads to the synthesis of specific proteins responsible for the physiological effects of estrogens, including the development and maintenance of the female reproductive system and secondary sex characteristics. In postmenopausal women, it replaces the declining endogenous estrogen, alleviating symptoms like vasomotor symptoms and vulvar/vaginal atrophy.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 10-15% (transdermal bypasses first-pass metabolism compared to oral)
Tmax:
Approximately 2-8 hours (for transdermal gel)
FoodEffect:
Not applicable for transdermal application.
Distribution:
Vd:
Approximately 1.2 L/kg
ProteinBinding:
Highly protein bound (>95%), primarily to sex hormone-binding globulin (SHBG) and albumin.
CnssPenetration:
Limited, but effects on CNS (e.g., mood, cognition) are known.
Elimination:
HalfLife:
Approximately 1-2 hours (for estradiol itself, but transdermal provides sustained levels)
Clearance:
High hepatic clearance
ExcretionRoute:
Primarily renal (as glucuronide and sulfate conjugates), some biliary excretion.
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Symptomatic relief may begin within weeks.
PeakEffect:
Full therapeutic effect for vasomotor symptoms may take several weeks to months.
DurationOfAction:
Daily application provides sustained therapeutic levels over 24 hours.
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. A substudy of the WHI study also reported an increased risk of stroke and deep vein thrombosis in postmenopausal women (50-79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (0.625 mg) alone relative to placebo. The WHIMS estrogen-alone ancillary study reported an increased risk of probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily oral conjugated estrogens (0.625 mg) alone relative to placebo. Other doses of oral conjugated estrogens and other dosage forms of estrogens were not studied in the WHI and WHIMS trials. In the absence of comparable data, these risks should be assumed to be similar for other doses of oral estrogens and other forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Side Effects
Serious 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 pain or upset, light-colored stools, vomiting, or yellow skin and eyes.
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades, yellow skin and eyes, fever with chills, bloating, or severe stomach upset or vomiting.
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe stomach upset or vomiting.
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision.
Weakness on one side of the body, difficulty speaking or thinking, balance problems, drooping on one side of the face, or blurred vision.
Changes in eyesight or loss of eyesight, bulging eyes, or changes in how contact lenses feel.
Breast lump, breast pain or tenderness, or nipple discharge.
Vaginal itching or discharge.
Abnormal vaginal bleeding.
Depression or mood changes.
Memory problems or loss.
Fever.
Difficulty urinating or changes in urine output.
Pain while urinating.
This medication may cause fluid retention or swelling in the body. Inform your doctor if you experience swelling, weight gain, or breathing difficulties.
Blood Clots and High Calcium Levels
Seek immediate medical attention if you experience:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, color changes, or pain in a leg or arm, or difficulty speaking or swallowing.
Signs of high calcium levels: weakness, confusion, fatigue, headache, stomach upset or vomiting, constipation, or bone pain.
Other Side Effects
Most medications can cause side effects, but many people experience none or only mild side effects. If you are concerned about any of the following side effects or if they persist, contact your doctor:
Dizziness or headache.
Hair loss.
Stomach upset or vomiting.
Constipation.
Stomach pain or cramps.
Bloating.
Enlarged or tender breasts.
Vaginal bleeding or spotting.
Painful periods.
Common cold symptoms.
Nose or throat irritation.
Weight gain or loss.
Joint pain.
Leg cramps.
Changes in sex drive.
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, 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 pain or upset, light-colored stools, vomiting, or yellow skin and eyes.
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades, yellow skin and eyes, fever with chills, bloating, or severe stomach upset or vomiting.
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe stomach upset or vomiting.
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision.
Weakness on one side of the body, difficulty speaking or thinking, balance problems, drooping on one side of the face, or blurred vision.
Changes in eyesight or loss of eyesight, bulging eyes, or changes in how contact lenses feel.
Breast lump, breast pain or tenderness, or nipple discharge.
Vaginal itching or discharge.
Abnormal vaginal bleeding.
Depression or mood changes.
Memory problems or loss.
Fever.
Difficulty urinating or changes in urine output.
Pain while urinating.
This medication may cause fluid retention or swelling in the body. Inform your doctor if you experience swelling, weight gain, or breathing difficulties.
Blood Clots and High Calcium Levels
Seek immediate medical attention if you experience:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, color changes, or pain in a leg or arm, or difficulty speaking or swallowing.
Signs of high calcium levels: weakness, confusion, fatigue, headache, stomach upset or vomiting, constipation, or bone pain.
Other Side Effects
Most medications can cause side effects, but many people experience none or only mild side effects. If you are concerned about any of the following side effects or if they persist, contact your doctor:
Dizziness or headache.
Hair loss.
Stomach upset or vomiting.
Constipation.
Stomach pain or cramps.
Bloating.
Enlarged or tender breasts.
Vaginal bleeding or spotting.
Painful periods.
Common cold symptoms.
Nose or throat irritation.
Weight gain or loss.
Joint pain.
Leg cramps.
Changes in sex drive.
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, 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 severe headache, dizziness, or fainting.
- Sudden vision changes (e.g., partial or complete loss of vision).
- Sudden numbness or weakness in an arm or leg, especially on one side of the body.
- Sudden chest pain, shortness of breath, or coughing up blood.
- Pain, swelling, or tenderness in one leg (especially calf).
- New breast lump, nipple discharge, or changes in breast skin.
- Unusual vaginal bleeding (especially after menopause).
- Yellowing of the skin or eyes (jaundice), dark urine, or severe abdominal pain (signs of liver problems).
- Severe mood changes or depression.
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. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, such as:
+ 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
Pregnancy or suspected pregnancy. Note: This medication should not be taken during pregnancy.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Do not initiate, stop, or adjust the dosage of any medication without 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. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, such as:
+ 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
Pregnancy or suspected pregnancy. Note: This medication should not be taken during pregnancy.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Do not initiate, stop, or adjust the dosage of any medication without 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 will be immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as it may increase your risk of developing blood clots. Additionally, if you have diabetes, you will need to closely monitor your blood sugar levels.
This medication may cause high blood pressure, so it is crucial to have your blood pressure checked regularly, as directed by your doctor. You should also have your blood work and bone density checked as recommended by your doctor.
Regular breast exams and gynecology check-ups are vital, and you should also 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 use, 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.
High triglyceride levels have been associated with this medication, so inform your doctor if you have a history of elevated triglyceride levels. This drug may also cause dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear.
This medication may interfere with certain laboratory tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Smoking can increase the risk of heart disease, so it is recommended that you do not smoke. Limit your alcohol consumption, and if you regularly drink grapefruit juice or eat grapefruit, discuss this with your doctor.
In some cases, this medication may affect growth in children and teenagers, so they may require regular growth checks. Consult with your doctor before using other medications or skin products, including soaps. When using the gel form of this medication, avoid applying sunscreen before or soon after application, and do not use sunscreen on the treated area for 7 consecutive days.
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects. If you are breastfeeding, discuss the potential risks to your baby with your doctor.
If you will be immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as it may increase your risk of developing blood clots. Additionally, if you have diabetes, you will need to closely monitor your blood sugar levels.
This medication may cause high blood pressure, so it is crucial to have your blood pressure checked regularly, as directed by your doctor. You should also have your blood work and bone density checked as recommended by your doctor.
Regular breast exams and gynecology check-ups are vital, and you should also 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 use, 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.
High triglyceride levels have been associated with this medication, so inform your doctor if you have a history of elevated triglyceride levels. This drug may also cause dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear.
This medication may interfere with certain laboratory tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Smoking can increase the risk of heart disease, so it is recommended that you do not smoke. Limit your alcohol consumption, and if you regularly drink grapefruit juice or eat grapefruit, discuss this with your doctor.
In some cases, this medication may affect growth in children and teenagers, so they may require regular growth checks. Consult with your doctor before using other medications or skin products, including soaps. When using the gel form of this medication, avoid applying sunscreen before or soon after application, and do not use sunscreen on the treated area for 7 consecutive days.
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects. If you are breastfeeding, discuss the potential risks to your baby with your doctor.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Breast tenderness
- Abdominal pain
- Drowsiness/fatigue
- Withdrawal bleeding (in females)
What to Do:
Seek immediate medical attention or call a poison control center (1-800-222-1222). Treatment is generally supportive; there is no specific antidote. Remove the gel and wash the application site.
Drug Interactions
Contraindicated Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole) - pharmacodynamic antagonism.
Major Interactions
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenobarbital, phenytoin, St. John's wort) - may significantly decrease estradiol levels, reducing efficacy.
- CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin) - may increase estradiol levels, potentially increasing adverse effects.
Moderate Interactions
- Thyroid hormone replacement therapy (e.g., levothyroxine) - Estrogens can increase thyroid-binding globulin (TBG), potentially increasing the need for thyroid hormone.
- Corticosteroids (e.g., prednisone) - Estrogens may decrease the metabolic clearance of corticosteroids, leading to increased effects.
- Oral anticoagulants (e.g., warfarin) - Estrogens may diminish the anticoagulant effect; monitor INR.
- Folic acid - May increase estradiol levels.
Minor Interactions
- Grapefruit juice - May inhibit CYP3A4, potentially increasing estradiol levels (less significant for transdermal).
Monitoring
Baseline Monitoring
Complete medical history and physical examination
Rationale: To identify contraindications, risk factors (e.g., cardiovascular disease, breast cancer), and establish baseline health status.
Timing: Prior to initiation of therapy.
Blood pressure
Rationale: Estrogens can affect blood pressure.
Timing: Prior to initiation.
Breast examination and mammography
Rationale: To screen for breast cancer, as estrogens can increase risk.
Timing: Prior to initiation, as per age-appropriate guidelines.
Pelvic examination and Pap test
Rationale: To screen for gynecological conditions, including endometrial cancer (if uterus intact).
Timing: Prior to initiation, as per age-appropriate guidelines.
Lipid profile
Rationale: Estrogens can affect lipid metabolism.
Timing: Prior to initiation.
Liver function tests
Rationale: Estrogens are metabolized by the liver and can affect liver function.
Timing: Prior to initiation, especially if history of liver dysfunction.
Routine Monitoring
Annual physical examination
Frequency: Annually
Target: N/A
Action Threshold: N/A
Blood pressure
Frequency: Annually, or more frequently if indicated.
Target: <130/80 mmHg (general target)
Action Threshold: Sustained elevation requiring intervention.
Breast examination and mammography
Frequency: Annually (breast exam); mammography as per age-appropriate guidelines (e.g., every 1-2 years).
Target: N/A
Action Threshold: New lumps, pain, or abnormal findings requiring further investigation.
Pelvic examination and Pap test
Frequency: As per age-appropriate guidelines (e.g., every 1-3 years for Pap test).
Target: N/A
Action Threshold: Abnormal bleeding, pain, or abnormal findings requiring further investigation.
Lipid profile
Frequency: Periodically, as clinically indicated.
Target: Individualized based on cardiovascular risk.
Action Threshold: Significant adverse changes requiring intervention.
Endometrial monitoring (if uterus intact)
Frequency: Annually, or if abnormal bleeding occurs.
Target: N/A
Action Threshold: Abnormal uterine bleeding (e.g., postmenopausal bleeding) requires evaluation to rule out endometrial pathology.
Symptom Monitoring
- Signs/symptoms of thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction): sudden chest pain, shortness of breath, sudden severe headache, sudden vision changes, numbness/weakness on one side of body, pain/swelling in leg.
- Signs/symptoms of breast cancer: new breast lump, skin changes, nipple discharge.
- Abnormal vaginal bleeding (especially postmenopausal bleeding).
- Signs/symptoms of liver dysfunction: jaundice, severe abdominal pain, dark urine, pale stools.
- Severe headache, migraine with aura.
- Fluid retention/edema.
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. There is no indication for estrogen therapy in pregnancy. Estrogen exposure during pregnancy has been associated with an increased risk of birth defects in the reproductive organs of female fetuses.
Trimester-Specific Risks:
First Trimester:
Potential for adverse effects on fetal development, particularly reproductive organs.
Second Trimester:
Not indicated; continued exposure may pose risks.
Third Trimester:
Not indicated; continued exposure may pose risks.
Lactation
Not recommended during lactation. Estrogens 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:
Risk level L4 (Potentially hazardous). May reduce milk supply and potentially affect the infant, though specific risks are not well-established.
Pediatric Use
Not indicated for use in pediatric patients. Safety and efficacy have not been established.
Geriatric Use
Use with caution in women 65 years of age or older. The Women's Health Initiative Memory Study (WHIMS) found an increased risk of probable dementia in postmenopausal women 65 years of age or older treated with conjugated estrogens alone or in combination with medroxyprogesterone acetate. The lowest effective dose for the shortest duration should be used, and the risks versus benefits should be carefully considered.
Clinical Information
Clinical Pearls
- Divigel is a transdermal estrogen, which bypasses first-pass hepatic metabolism, potentially leading to a more favorable lipid profile and lower risk of VTE compared to oral estrogens, though this is not definitively proven across all studies.
- Always use the lowest effective dose for the shortest duration consistent with treatment goals, especially given the Black Box Warning risks.
- For women with an intact uterus, a progestin must be co-administered to reduce the risk of endometrial hyperplasia and cancer.
- Patients should be educated on proper application technique to ensure consistent dosing and minimize transfer to others.
- Regular monitoring, including breast exams, mammograms, and pelvic exams, is crucial during therapy.
- Counsel patients on the signs and symptoms of serious adverse events (e.g., blood clots, stroke, heart attack, breast cancer) and when to seek immediate medical attention.
Alternative Therapies
- Selective Estrogen Receptor Modulators (SERMs) for specific indications (e.g., ospemifene for dyspareunia, bazedoxifene/conjugated estrogens for vasomotor symptoms and osteoporosis prevention)
- Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine)
- Lifestyle modifications (e.g., diet, exercise, avoiding triggers for hot flashes)
- Vaginal moisturizers and lubricants for vaginal atrophy.
Cost & Coverage
Average Cost:
$150 - $300 per 30-day supply (e.g., 30 packets)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (Brand name), Tier 1 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, 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 for more information. If you have any questions or concerns about your 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 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.