Divigel 0.5mg/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
Hormone Replacement Therapy (HRT)
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 is used by women after menopause to help reduce hot flashes and night sweats, and to help prevent bone thinning (osteoporosis). You apply a small amount of the gel to your skin, usually on your thigh or calf, once a day. It works by replacing the estrogen your body no longer makes 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 is essential to use this medication as directed and follow all instructions carefully.
Application Instructions
Do not take this medication by mouth. It is for topical 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 to maintain a consistent routine.
Before and after applying the medication, wash your hands thoroughly.
Apply the medication to clean, dry, and healthy skin on your thigh.
Certain products have specific application areas, so be sure to read the package insert for detailed instructions.
Do not apply the medication to skin with any problems or irritations.
Avoid applying the medication to your face, breast, or vagina.
Special Instructions for Pump and Packet Products
If you are using a pump product, prime it before the first use, following the instructions in the package insert.
If you are using a packet product, follow the instructions for application.
Precautions and Safety Measures
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.
Allow the medication to 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 minimize skin irritation.
Storage and Disposal
Store the medication at room temperature in a dry place, away from bathrooms and heat sources.
Protect the medication from heat, open flames, and sparks.
Keep all medications in a safe and secure location, 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 is less than 12 hours until your next scheduled dose, skip the missed dose and resume your regular application schedule.
* Do not apply two doses at the same time or use extra doses to make up for a missed dose.
To use this medication correctly, follow your doctor's instructions and read all the information provided. It is essential to use this medication as directed and follow all instructions carefully.
Application Instructions
Do not take this medication by mouth. It is for topical 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 to maintain a consistent routine.
Before and after applying the medication, wash your hands thoroughly.
Apply the medication to clean, dry, and healthy skin on your thigh.
Certain products have specific application areas, so be sure to read the package insert for detailed instructions.
Do not apply the medication to skin with any problems or irritations.
Avoid applying the medication to your face, breast, or vagina.
Special Instructions for Pump and Packet Products
If you are using a pump product, prime it before the first use, following the instructions in the package insert.
If you are using a packet product, follow the instructions for application.
Precautions and Safety Measures
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.
Allow the medication to 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 minimize skin irritation.
Storage and Disposal
Store the medication at room temperature in a dry place, away from bathrooms and heat sources.
Protect the medication from heat, open flames, and sparks.
Keep all medications in a safe and secure location, 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 is less than 12 hours until your next scheduled dose, skip the missed dose and resume your regular application schedule.
* Do not apply two doses at the same time or use extra doses to make up for a missed dose.
Lifestyle & Tips
- Apply the gel to clean, dry, unbroken skin on your thigh or calf. Do not apply to breasts or face.
- Allow the gel to dry for at least 5 minutes before dressing. Avoid contact with clothing until dry.
- Wash hands thoroughly after application to avoid transferring the gel to others.
- Avoid contact with eyes, mouth, and other sensitive areas.
- Do not apply to skin that is irritated or broken.
- Avoid swimming or showering for at least 1 hour after application.
- Inform your doctor about all medications, supplements, and herbal products you are taking.
- Regularly perform breast self-exams and attend scheduled mammograms and doctor visits.
- Maintain a healthy lifestyle, including a balanced diet rich in calcium and vitamin D, and regular weight-bearing exercise, especially for bone health.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
0.5 mg estradiol (one 0.5 mg packet or 1.25 g of 0.04% gel) applied once daily to the thigh or calf
Dose Range:
0.25 - 1.5 mg
Condition-Specific Dosing:
vasomotorSymptoms:
Initial dose 0.25 mg to 1.0 mg daily; adjust based on clinical response. For Divigel 0.5mg/day, the standard dose is 0.5 mg daily.
osteoporosisPrevention:
0.25 mg to 1.0 mg daily, typically 0.5 mg to 1.0 mg daily. Lowest effective dose should be used.
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; estradiol is primarily metabolized by the liver and excreted renally. Accumulation of metabolites may occur.
Dialysis:
Not available; use with caution.
Hepatic Impairment:
Mild:
Use with caution; estrogens are extensively metabolized by the liver.
Moderate:
Contraindicated due to impaired estrogen metabolism and increased risk of cholestasis.
Severe:
Contraindicated due to impaired estrogen metabolism and increased risk of cholestasis.
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, including the reproductive tract, breast, bone, and brain. This binding leads to gene transcription and protein synthesis, mediating the physiological effects of estrogen, such as reducing vasomotor symptoms and preventing bone loss.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 10-15% (transdermal, relative to oral), but avoids first-pass metabolism, leading to a more favorable estradiol to estrone ratio.
Tmax:
Approximately 2-4 hours after transdermal application.
FoodEffect:
Not applicable for transdermal gel.
Distribution:
Vd:
Approximately 1.2 L/kg (for estradiol)
ProteinBinding:
Approximately 98% (primarily to sex hormone-binding globulin (SHBG) and albumin).
CnssPenetration:
Limited, but estrogen receptors are present in the CNS.
Elimination:
HalfLife:
Approximately 1-2 hours (for estradiol after transdermal absorption, but effective half-life is longer due to sustained absorption from skin reservoir).
Clearance:
Approximately 650-1000 mL/min (for estradiol).
ExcretionRoute:
Primarily renal (as glucuronide and sulfate conjugates); small amount fecal.
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Within days to weeks for symptom relief.
PeakEffect:
Typically within 4-8 weeks for full therapeutic effect.
DurationOfAction:
24 hours (with daily application).
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 5.2 years of treatment with conjugated equine estrogens (CEE) [0.625 mg] alone or in combination with medroxyprogesterone acetate (MPA) [0.625 mg CEE plus 2.5 mg MPA] compared 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 CEE alone or in combination with CEE plus MPA compared to placebo. Other doses of oral estrogens and other dosage forms of estrogens were not studied in the WHI and, in the absence of comparable data, these risks should be assumed to be similar. 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 changes, 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 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 signs of high calcium levels, such as:
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 minor 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, 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 changes, 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 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 signs of high calcium levels, such as:
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 minor 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, 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 or migraine
- Sudden vision changes (e.g., partial or complete loss of vision)
- Sudden chest pain, shortness of breath, or coughing up blood
- Pain, swelling, or redness in one leg (especially calf or thigh)
- Yellowing of the skin or eyes (jaundice)
- New breast lump or nipple discharge
- Unusual vaginal bleeding or spotting after menopause
- Severe abdominal pain
- Signs of an allergic reaction (e.g., rash, itching, swelling, severe dizziness, trouble breathing)
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 estrogen-dependent
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 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 estrogen-dependent
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 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, discuss this with your doctor, as prolonged inactivity may increase your risk of developing blood clots. If you have diabetes, it is crucial 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. Additionally, have your blood work and bone density checked as directed 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 drug. If you have a history of high triglyceride levels, inform your doctor. This medication may cause dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and to use sunscreen and protective clothing and eyewear.
This medication may affect certain laboratory tests, so inform all your healthcare providers and lab workers that you are taking this drug. Avoid smoking, as it increases the risk of heart disease, and limit your alcohol consumption. If you regularly consume grapefruit juice or eat grapefruit, discuss this 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, consult with your doctor to discuss any potential risks to your baby.
If you will be immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as prolonged inactivity may increase your risk of developing blood clots. If you have diabetes, it is crucial 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. Additionally, have your blood work and bone density checked as directed 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 drug. If you have a history of high triglyceride levels, inform your doctor. This medication may cause dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and to use sunscreen and protective clothing and eyewear.
This medication may affect certain laboratory tests, so inform all your healthcare providers and lab workers that you are taking this drug. Avoid smoking, as it increases the risk of heart disease, and limit your alcohol consumption. If you regularly consume grapefruit juice or eat grapefruit, discuss this 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, consult with your doctor to discuss any potential risks to your baby.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Breast tenderness
- Abdominal pain
- Drowsiness/fatigue
- Withdrawal bleeding (in women)
What to Do:
There is no specific antidote. Treatment is symptomatic and supportive. Remove the gel from the skin by washing the area. In case of suspected overdose, contact a poison control center or seek immediate medical attention. Call 1-800-222-1222 for Poison Control.
Drug Interactions
Major Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) - concurrent use would counteract their effect.
- Tranexamic acid (increased risk of thrombosis).
Moderate Interactions
- CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) - may decrease estradiol levels.
- CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, ritonavir, grapefruit juice) - may increase estradiol levels.
- Thyroid hormone replacement (e.g., levothyroxine) - estrogens can increase thyroid-binding globulin, potentially increasing thyroid hormone requirements.
- Corticosteroids (e.g., prednisone) - estrogens may decrease corticosteroid clearance, leading to increased effects.
- Oral anticoagulants (e.g., warfarin) - estrogens may alter anticoagulant effects; monitor INR.
Minor Interactions
- Folic acid (may increase folate requirements).
Monitoring
Baseline Monitoring
Complete medical history and physical examination (including blood pressure, breast and pelvic exam)
Rationale: To assess overall health, identify contraindications, and establish baseline for future comparisons.
Timing: Prior to initiation of therapy.
Mammography
Rationale: To screen for breast cancer before initiating estrogen therapy.
Timing: Prior to initiation, as appropriate for age and risk factors.
Lipid profile (cholesterol, triglycerides)
Rationale: Estrogens can affect lipid metabolism; establish baseline.
Timing: Prior to initiation.
Liver function tests (LFTs)
Rationale: To assess hepatic function, especially given hepatic metabolism of estradiol.
Timing: Prior to initiation, if clinically indicated.
Routine Monitoring
Blood pressure
Frequency: Annually or as clinically indicated.
Target: Normal limits (e.g., <120/80 mmHg)
Action Threshold: Sustained elevation requiring intervention.
Breast examination and mammography
Frequency: Annually (breast exam); mammography as per national guidelines.
Target: No new masses or suspicious findings.
Action Threshold: New breast lump, nipple discharge, or suspicious mammogram findings.
Pelvic examination
Frequency: Annually or as clinically indicated.
Target: No abnormal findings (e.g., uterine bleeding, ovarian masses).
Action Threshold: Abnormal uterine bleeding, pelvic pain, or suspicious findings.
Lipid profile
Frequency: Periodically, as clinically indicated.
Target: Individualized based on cardiovascular risk.
Action Threshold: Significant adverse changes in lipid profile.
Bone mineral density (BMD)
Frequency: Every 1-2 years for osteoporosis prevention, as clinically indicated.
Target: Stable or improved BMD.
Action Threshold: Significant bone loss despite therapy.
Symptom Monitoring
- Persistent or recurrent vaginal bleeding
- New breast lumps or pain
- Severe headache or migraine
- Vision changes
- Leg pain, swelling, or tenderness (signs of DVT)
- Chest pain or shortness of breath (signs of PE, MI)
- Yellowing of skin or eyes (jaundice)
- Abdominal pain or swelling
- Mood changes or depression
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. Estrogen use during pregnancy is associated with an increased risk of birth defects in the fetus, including cardiovascular defects and limb reduction defects, if used during the first trimester. There is no indication for estrogen therapy during pregnancy.
Trimester-Specific Risks:
First Trimester:
Increased risk of birth defects (e.g., cardiovascular, limb reduction).
Second Trimester:
Not indicated; potential for adverse effects on fetal development.
Third Trimester:
Not indicated; potential for adverse effects on fetal development.
Lactation
Contraindicated during lactation. Estrogens are excreted in human milk and can reduce the quantity and quality of breast milk. Potential adverse effects on the nursing infant are unknown but possible.
Infant Risk:
High (L5 - Contraindicated)
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 WHIMS study showed an increased risk of probable dementia in women 65 years of age or older receiving CEE alone or CEE plus MPA. The lowest effective dose for the shortest duration should be used. Close monitoring for adverse effects is recommended.
Clinical Information
Clinical Pearls
- Transdermal estradiol avoids first-pass hepatic metabolism, potentially leading to a more favorable lipid profile and lower risk of venous thromboembolism compared to oral estrogens, though risks still exist.
- The 0.5 mg/day dose of Divigel is a common starting point for managing vasomotor symptoms, but titration may be needed based on individual response and tolerability.
- For women with an intact uterus, a progestin must be co-administered with Divigel to reduce the risk of endometrial hyperplasia and cancer.
- Patients should be educated on the proper application technique to ensure consistent absorption and minimize transfer to others.
- Regular re-evaluation of the need for continued therapy is crucial, as HRT should be used for the shortest duration consistent with treatment goals.
Alternative Therapies
- Selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) for vasomotor symptoms (e.g., paroxetine, venlafaxine)
- Gabapentin for vasomotor symptoms
- Clonidine for vasomotor symptoms
- Non-pharmacological approaches for vasomotor symptoms (e.g., lifestyle modifications, cognitive behavioral therapy)
- Bisphosphonates, denosumab, teriparatide, romosozumab for osteoporosis prevention (if HRT is contraindicated or not preferred)
Cost & Coverage
Average Cost:
$150 - $300 per 30 packets (0.5 mg)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (for brand); Tier 1 (for 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. If you have any questions or concerns about your medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the substance taken, the amount, and the time it occurred.