Divigel 0.1% (1mg/day) Top Gel
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?
Estradiol gel is a medication containing the hormone estrogen. It is applied to the skin to help relieve symptoms of menopause, such as hot flashes and vaginal dryness. It works by replacing the estrogen that your body naturally stops making after menopause.
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 skin use 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, and healthy skin on the thigh.
Certain products are designed for specific areas of the body. Be sure to read the package insert to understand where to apply this medication.
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 Pump or Packet Products
If you're using a pump product, prime it before the first use, following the instructions in the package insert.
If you're using a packet product, follow the instructions provided.
Safety Precautions
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.
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 applying the medication.
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 your next scheduled dose, skip the missed dose and continue with 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 skin use 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, and healthy skin on the thigh.
Certain products are designed for specific areas of the body. Be sure to read the package insert to understand where to apply this medication.
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 Pump or Packet Products
If you're using a pump product, prime it before the first use, following the instructions in the package insert.
If you're using a packet product, follow the instructions provided.
Safety Precautions
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.
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 applying the medication.
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 your next scheduled dose, skip the missed dose and continue with 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 once 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 and mucous membranes.
- Avoid applying to irritated or broken skin.
- If you have a uterus, your doctor will likely prescribe a progestin to be taken with estradiol to reduce the risk of uterine cancer.
- Regular exercise and a healthy diet are important for overall health during menopause.
- Smoking increases the risk of blood clots and other serious side effects; avoid smoking while on estrogen therapy.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
0.25 g (0.25 mg estradiol) to 1.25 g (1.25 mg estradiol) applied once daily to the skin of one thigh. The 0.1% formulation implies 1mg/day is 1g of gel.
Dose Range:
0.25 - 1.25 mg
Condition-Specific Dosing:
vasomotor_symptoms:
Initial dose 0.25 g (0.25 mg estradiol) once daily. May be adjusted based on clinical response to 0.5 g (0.5 mg estradiol) or 1.0 g (1.0 mg estradiol) once daily. For Divigel 0.1% (1mg/day), this refers to 1g of gel.
vulvar_vaginal_atrophy:
Initial dose 0.25 g (0.25 mg estradiol) once daily. May be adjusted based on clinical response to 0.5 g (0.5 mg estradiol) or 1.0 g (1.0 mg estradiol) once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended
Moderate:
No specific dose adjustment recommended
Severe:
Use with caution; monitor for adverse effects
Dialysis:
Not specifically studied; use with caution
Hepatic Impairment:
Mild:
No specific dose adjustment recommended
Moderate:
Use with caution; monitor for adverse effects
Severe:
Contraindicated in severe liver disease
Confidence:
Medium
Pharmacology
Mechanism of Action
Estradiol is the primary estrogen secreted by the human ovary. It binds to and activates nuclear estrogen receptors (ERΞ± and ERΞ²) in target tissues, forming a complex that interacts with estrogen response elements on DNA. This interaction modulates gene transcription, leading 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 menopausal women, it replaces declining endogenous estrogen levels to alleviate symptoms such as hot flashes and vaginal atrophy.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 10-15% (transdermal, relative to oral)
Tmax:
Approximately 2-4 hours
FoodEffect:
Not applicable for transdermal gel
Distribution:
Vd:
Approximately 1.2 L/kg
ProteinBinding:
Approximately 98% (primarily to sex hormone-binding globulin (SHBG) and albumin)
CnssPenetration:
Limited for therapeutic effects, but estrogens can influence CNS function
Elimination:
HalfLife:
Approximately 24-36 hours (for estradiol, after transdermal application)
Clearance:
Not readily quantifiable for transdermal application due to sustained absorption
ExcretionRoute:
Mainly renal (as glucuronide and sulfate conjugates), some fecal
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Symptomatic relief may begin within weeks, full effect within 2-4 weeks
PeakEffect:
Peak plasma concentrations reached within 2-4 hours post-application
DurationOfAction:
Approximately 24 hours (due to daily application)
Safety & Warnings
BLACK BOX WARNING
Estrogens and Estrogen Plus Progestin Therapy:
1. Estrogen-Alone Therapy: There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurrent abnormal genital bleeding. Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.
2. Estrogen Plus Progestin Therapy: Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) study reported an increased risk of stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and breast cancer 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. Other doses of oral conjugated estrogens and medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, 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.
1. Estrogen-Alone Therapy: There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurrent abnormal genital bleeding. Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.
2. Estrogen Plus Progestin Therapy: Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) study reported an increased risk of stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and breast cancer 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. Other doses of oral conjugated estrogens and medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, 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
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 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 vision or loss of vision, 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 other 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, 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 this medication. Contact your doctor right away if you experience:
Weakness
Confusion
Fatigue
Headache
Stomach upset or vomiting
Constipation
Bone pain
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only mild ones. 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, 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 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 vision or loss of vision, 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 other 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, 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 this medication. Contact your doctor right away if you experience:
Weakness
Confusion
Fatigue
Headache
Stomach upset or vomiting
Constipation
Bone pain
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only mild ones. 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, 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 severe headache or migraine
- Sudden vision changes (e.g., partial or complete loss of vision)
- Sudden numbness or weakness on one side of the body
- Slurred speech or difficulty speaking
- Chest pain, pressure, or discomfort
- Shortness of breath
- Pain, swelling, or redness in one leg (especially the calf)
- Abnormal vaginal bleeding (e.g., spotting, breakthrough bleeding, prolonged bleeding)
- Lump in the breast
- Yellowing of the skin or eyes (jaundice)
- 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. 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 potential 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 issues 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 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. 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 potential 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 issues 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 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 will be immobile for extended periods, such as during long trips, bedrest after surgery, or illness, consult with your doctor, as this may increase your risk of developing blood clots. Additionally, if you have diabetes, you will need to closely monitor your blood sugar levels.
Be aware that medications like this one can cause high blood pressure. Follow your doctor's instructions for regular blood pressure checks. You should also have your blood work and bone density checked as directed by your doctor.
Regular breast exams and gynecology check-ups are crucial, 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. If you have a history of high triglyceride levels, inform your doctor. 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 sunscreen and protective clothing and eyewear.
This medication may interfere with certain laboratory tests, so be sure to 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, consult with your doctor.
In some cases, this medication may affect growth in children and teenagers, and 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, consult with your doctor, as this may increase your risk of developing blood clots. Additionally, if you have diabetes, you will need to closely monitor your blood sugar levels.
Be aware that medications like this one can cause high blood pressure. Follow your doctor's instructions for regular blood pressure checks. You should also have your blood work and bone density checked as directed by your doctor.
Regular breast exams and gynecology check-ups are crucial, 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. If you have a history of high triglyceride levels, inform your doctor. 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 sunscreen and protective clothing and eyewear.
This medication may interfere with certain laboratory tests, so be sure to 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, consult with your doctor.
In some cases, this medication may affect growth in children and teenagers, and 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 women)
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 from the skin if possible.
Drug Interactions
Contraindicated Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole) - concurrent use would counteract the effect of the aromatase inhibitor
- Tamoxifen - may reduce efficacy of tamoxifen
Major Interactions
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenobarbital, St. John's Wort) - may decrease estradiol levels and efficacy
- CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, ritonavir) - may increase estradiol levels and risk of adverse effects
- Thyroid hormone replacement therapy (e.g., levothyroxine) - estrogens can increase thyroid-binding globulin, requiring increased thyroid hormone dose
- Corticosteroids (e.g., prednisone) - estrogens may decrease corticosteroid clearance, leading to increased effects
Moderate Interactions
- Oral anticoagulants (e.g., warfarin) - estrogens may alter anticoagulant effects, requiring INR monitoring
- Folic acid - estrogens may increase folate requirements
- Hydantoins (e.g., phenytoin) - may decrease estrogen levels
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Complete medical history and physical examination
Rationale: To identify contraindications, risk factors (e.g., cardiovascular disease, breast cancer, VTE), 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
Lipid profile
Rationale: Estrogens can affect lipid metabolism.
Timing: Prior to initiation of therapy
Liver function tests
Rationale: Contraindicated in severe liver disease; caution in moderate impairment.
Timing: Prior to initiation of therapy
Mammogram
Rationale: To screen for pre-existing breast abnormalities; estrogens may increase breast cancer risk.
Timing: Prior to initiation of therapy
Pelvic examination and Pap test
Rationale: To screen for cervical and uterine abnormalities; estrogens may increase endometrial cancer risk (if unopposed).
Timing: Prior to initiation of therapy
Routine Monitoring
Annual physical examination (including breast and pelvic exam)
Frequency: Annually
Target: Normal findings
Action Threshold: Any new or concerning findings require further investigation
Mammogram
Frequency: As clinically indicated, typically annually or biennially based on age and risk factors
Target: Normal findings
Action Threshold: Abnormal findings require further investigation
Blood pressure
Frequency: Annually or more frequently if clinically indicated
Target: <130/80 mmHg
Action Threshold: Sustained elevation requires evaluation and management
Lipid profile
Frequency: Periodically, as clinically indicated
Target: Individualized based on cardiovascular risk
Action Threshold: Significant changes or abnormal values require evaluation
Symptom Monitoring
- Abnormal vaginal bleeding (spotting, breakthrough bleeding, prolonged bleeding)
- Breast lumps or changes
- Symptoms of deep vein thrombosis (DVT) or pulmonary embolism (PE): leg pain, swelling, redness; sudden chest pain, shortness of breath
- Symptoms of stroke: sudden severe headache, vision changes, weakness/numbness on one side of body, speech difficulty
- Symptoms of myocardial infarction (MI): chest pain, discomfort, shortness of breath, pain radiating to arm/jaw
- Symptoms of liver dysfunction: jaundice, severe abdominal pain
- Severe headache or migraine exacerbation
- Changes in mood or depression
Special Patient Groups
Pregnancy
Contraindicated during pregnancy. Estrogen therapy during pregnancy is associated with an increased risk of birth defects and should not be used.
Trimester-Specific Risks:
First Trimester:
Potential for adverse effects on fetal development, including cardiovascular and limb defects.
Second Trimester:
Not indicated; continued exposure may lead to adverse effects.
Third Trimester:
Not indicated; continued exposure may lead to adverse effects.
Lactation
Not recommended during lactation. Estrogens are excreted in breast milk and may reduce the quantity and quality of breast milk. Potential adverse effects on the nursing infant are unknown but possible.
Infant Risk:
L4 (Possibly hazardous). Potential for adverse effects on infant, including feminization or effects on development. May decrease milk production.
Pediatric Use
Not indicated for use in pediatric patients. Safety and efficacy have not been established.
Geriatric Use
Use with caution in women aged 65 years and older. The Women's Health Initiative (WHI) study showed an increased risk of stroke and dementia in women 65 years and older receiving estrogen-alone or estrogen plus progestin therapy. Prescribe the lowest effective dose for the shortest duration consistent with treatment goals.
Clinical Information
Clinical Pearls
- Divigel is a transdermal gel, which bypasses first-pass hepatic metabolism, potentially leading to a more favorable lipid profile and lower risk of VTE compared to oral estrogens, though risks still exist.
- Ensure patients understand the correct application technique: apply to a clean, dry area of one thigh, allow to dry completely, and wash hands thoroughly.
- Emphasize the importance of using a progestin concurrently if the patient has an intact uterus to mitigate the risk of endometrial hyperplasia and cancer.
- Counsel patients on the serious risks associated with estrogen therapy, including cardiovascular events, stroke, VTE, and breast cancer, as outlined in the Black Box Warning.
- Regular follow-up and monitoring are crucial to assess efficacy, manage side effects, and re-evaluate the need for continued therapy.
Alternative Therapies
- Oral estrogens (e.g., conjugated estrogens, estradiol tablets)
- Estrogen-progestin combination pills
- Selective Estrogen Receptor Modulators (SERMs) (e.g., ospemifene for dyspareunia, bazedoxifene/conjugated estrogens for vasomotor symptoms and osteoporosis)
- Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine)
- Lifestyle modifications (e.g., diet, exercise, stress reduction, avoiding triggers for hot flashes)
Cost & Coverage
Average Cost:
Varies, typically $100-$200 per 30-day supply (30 x 1g packets or 1 x 28g pump)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (Brand), Tier 1 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor promptly. 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 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 details about the medication taken, the amount, and the time it occurred.