Estradiol 0.075mg Patch (twice Wk)

Estradiol is the primary estrogen secreted by the human ovary. It binds to and activates estrogen receptors (ERα and ERβ) in target tissues, including the reproductive organs, breast, bone, and brain. This binding leads to a conformational change in the receptor, allowing it to interact with specific DNA sequences (estrogen response elements) and co-activator proteins, thereby regulating gene transcription and protein synthesis. In postmenopausal women, estrogen replacement alleviates symptoms of estrogen deficiency such as vasomotor symptoms and vulvar/vaginal atrophy, and helps prevent bone loss.

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 experience any of the following symptoms, contact your doctor or seek medical attention immediately:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of gallbladder problems, such as:
+ Pain in the upper right belly area, right shoulder area, or between the shoulder blades
+ Yellow skin or eyes
+ Fever with chills
+ Bloating
+ Severe upset stomach or vomiting
Signs of pancreatitis (pancreas problem), including:
+ Severe stomach pain
+ Severe back pain
+ Severe upset stomach or vomiting
Signs of high blood pressure, such as:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Weakness on one side of the body
Trouble speaking or thinking
Changes in balance
Drooping on one side of the face
Blurred eyesight
Eyesight changes or loss
Bulging eyes
Changes in how contact lenses feel
Breast lump, pain, or soreness
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, leading to swelling or weight gain. If you experience swelling, weight gain, or trouble breathing, inform your doctor.

Blood Clots and High Calcium Levels

Seek immediate medical attention if you experience signs of a blood clot, such as:
Chest pain or pressure
Coughing up blood
Shortness of breath
Swelling, warmth, numbness, changes in color, or pain in a leg or arm
Trouble speaking or swallowing

High calcium levels can occur in some people with cancer taking this medication. If you experience signs of high calcium levels, such as:
Weakness
Confusion
Fatigue
Headache
Upset stomach or vomiting
Constipation
Bone pain
contact your doctor right away.

Other Possible Side Effects

Most people do not experience severe side effects, and some may have only minor side effects. If you experience any of the following side effects, contact your doctor or seek medical attention if they bother you or do not go away:
Dizziness or headache
Hair loss
Upset stomach or vomiting
Constipation
Stomach pain or cramps
Bloating
Enlarged or tender breasts
Vaginal bleeding or spotting
Painful periods
Signs of a common cold
Nose or throat irritation
Weight gain or loss
Joint pain
Leg cramps
Changes in sex interest
Irritation at the site of application

Reporting Side Effects

If you have questions about side effects or experience any side effects not listed here, 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.

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 consulting your doctor first.

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 if so, will instruct you on when to resume taking it after the surgery or procedure.

If you anticipate being immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as prolonged inactivity may increase your risk of developing blood clots. Additionally, if you have diabetes (high blood sugar), 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. You should also 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, ovarian cancer, and others, 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, so inform your doctor if you have a history of elevated triglyceride levels. This medication may 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 when going outside.

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. 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.

For optimal effectiveness, use this medication in conjunction with calcium and vitamin D supplements and engage in weight-bearing exercises, such as walking or physical therapy, as directed by your doctor. Adhere to the diet and exercise plan recommended by your doctor.

In some cases, this medication may affect growth in children and teenagers, so they may require regular growth checks. Discuss this with your doctor. If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects. Finally, if you are breastfeeding, consult your doctor to discuss any potential risks to your baby.

• Aromatase inhibitors (e.g., Anastrozole, Letrozole, Exemestane) - concurrent use would counteract the effect of the aromatase inhibitor.
• Tamoxifen (concurrent use may increase risk of thromboembolic events and alter efficacy of tamoxifen).

• CYP3A4 inducers (e.g., Rifampin, Carbamazepine, Phenytoin, Phenobarbital, St. John's Wort): May significantly decrease estradiol plasma concentrations, leading to reduced therapeutic effect and potential for breakthrough bleeding. Consider alternative therapies or dose adjustments.
• CYP3A4 inhibitors (e.g., Ketoconazole, Itraconazole, Ritonavir, Clarithromycin, Grapefruit juice): May increase estradiol plasma concentrations, potentially increasing adverse effects. Monitor for increased estrogenic effects.
• Thyroid hormone replacement (e.g., Levothyroxine): Estrogens can increase thyroid-binding globulin (TBG) levels, leading to increased circulating thyroid hormone and potentially increased thyroid hormone requirements. Monitor thyroid function and adjust thyroid hormone dose as needed.
• Anticoagulants (e.g., Warfarin): Estrogens may decrease the anticoagulant effect of warfarin. Close monitoring of INR/PT is recommended, and warfarin dose adjustment may be necessary.
• Lamotrigine: Estrogens can decrease lamotrigine plasma concentrations, potentially leading to loss of seizure control. Monitor lamotrigine levels and adjust dose as needed.

• Corticosteroids (e.g., Prednisone): Estrogens may decrease the hepatic clearance of corticosteroids, leading to increased plasma concentrations and enhanced effects. Monitor for corticosteroid toxicity.
• Cyclosporine: Estrogens may inhibit the metabolism of cyclosporine, leading to increased plasma concentrations and potential for toxicity. Monitor cyclosporine levels.
• Folic acid: Estrogens may interfere with folate metabolism.
• Bosentan: May decrease estradiol levels.

• Not available

• Unusual vaginal bleeding or spotting
• New breast lump or changes in breasts
• Pain, swelling, or tenderness in one leg (signs of DVT)
• Sudden chest pain, shortness of breath, or coughing up blood (signs of PE)
• Sudden severe headache, dizziness, vision changes, slurred speech, weakness or numbness in an arm or leg (signs of stroke)
• Chest pain or discomfort, pain radiating to arm, back, neck, jaw, or stomach, shortness of breath, cold sweat, nausea, lightheadedness (signs of MI)
• Yellowing of skin or eyes (jaundice)
• Severe abdominal pain
• Mood changes, depression

Contraindicated. Estradiol is not indicated for use in pregnancy. There is no indication for estrogen therapy during pregnancy, and there is evidence of potential harm to the fetus. Exposure to estrogens during pregnancy has been associated with an increased risk of congenital anomalies in the reproductive organs of male and female fetuses.

Not recommended. Estradiol is excreted in human milk and may decrease milk production and quality. Potential adverse effects on the breastfed infant have been reported (e.g., jaundice, breast enlargement).

Not indicated for use in pediatric patients for hormone replacement therapy, except in specific cases of primary ovarian failure or hypogonadism, where dosing is highly individualized and typically initiated at lower doses. The 0.075 mg patch strength is generally too high for initial pediatric use.

Use with caution. Women 65 years of age or older may be at increased risk of probable dementia with estrogen therapy. The lowest effective dose for the shortest duration should be used. Monitor closely for cardiovascular events, stroke, and breast cancer. No specific dose adjustment based solely on age, but individual risk factors should be carefully assessed.

• Ensure patients understand the twice-weekly application schedule (e.g., change every 3-4 days) and proper patch application technique (clean, dry skin, rotate sites).
• Emphasize the importance of regular follow-up appointments and screenings (mammograms, pelvic exams) due to the black box warnings.
• 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.
• For women with an intact uterus, a progestin must be co-administered to reduce the risk of endometrial hyperplasia and cancer.
• Transdermal estradiol bypasses first-pass hepatic metabolism, which may result in a more favorable lipid profile and lower risk of venous thromboembolism compared to oral estrogens, though risks still exist.
• Adherence is crucial for consistent hormone levels and symptom control. Provide clear instructions on what to do if a patch falls off or a dose is missed.

• Other systemic estrogen formulations (oral tablets, vaginal rings, gels, sprays)
• Local vaginal estrogen products (creams, tablets, rings) for isolated vaginal symptoms
• Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine)
• Selective Estrogen Receptor Modulators (SERMs) like Ospemifene (for dyspareunia) or Bazedoxifene/Conjugated Estrogens (Duavee, for vasomotor symptoms and osteoporosis prevention)
• Bisphosphonates or other anti-resorptive agents for osteoporosis prevention/treatment (if HRT is not suitable)

If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.