Divigel 0.25mg/day Top Gel Pk

Estradiol is the primary estrogen produced by the human ovary. It binds to and activates nuclear estrogen receptors (ERα and ERβ) in target tissues, leading to gene transcription and protein synthesis. This results in the expression of estrogen-specific physiological effects, including the development and maintenance of the female reproductive system and secondary sex characteristics. In postmenopausal women, it replaces the declining endogenous estrogen levels to alleviate menopausal symptoms.

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, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or severe upset stomach or vomiting
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe upset stomach or vomiting
Signs of high blood pressure: severe headache or dizziness, passing out, or changes in eyesight
Weakness on one side of the body, trouble speaking or thinking, changes in balance, drooping on one side of the face, or blurred eyesight
Eyesight changes or loss, bulging eyes, or changes in how contact lenses feel
Breast lump, breast pain or soreness, 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
Trouble speaking or swallowing

High calcium levels have been reported in some people with cancer taking medications like this one. Contact your doctor right away if you experience:
Weakness
Confusion
Fatigue
Headache
Upset stomach 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
Upset stomach or vomiting
Constipation
Stomach pain or cramps
Bloating
Enlarged breasts
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 interest

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.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, including:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack
+ Stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
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. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.

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. 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, 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 avoid sun exposure, sunlamps, and tanning beds, and use protective measures like sunscreen, clothing, and eyewear.

Be aware that this medication may affect 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 essential to avoid smoking. 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. Finally, if you are breastfeeding, consult with your doctor to discuss any potential risks to your baby.

• Aromatase inhibitors (e.g., anastrozole, letrozole) - concurrent use would counteract the effect of the aromatase inhibitor.
• Fulvestrant - concurrent use would counteract the effect of fulvestrant.

• CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) - may decrease estradiol levels, reducing efficacy.
• CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir, grapefruit juice) - may increase estradiol levels, increasing risk of adverse effects.
• Thyroid hormone replacement therapy (e.g., levothyroxine) - estrogens can increase thyroid-binding globulin (TBG), requiring increased thyroid hormone dose.
• Anticoagulants (e.g., warfarin) - estrogens may decrease the anticoagulant effect of warfarin; monitor INR.

• Corticosteroids (e.g., prednisone) - estrogens may decrease the clearance of corticosteroids, leading to increased effects.
• Cyclosporine - estrogens may inhibit the metabolism of cyclosporine, leading to increased plasma concentrations and potential toxicity.
• Lamotrigine - estrogens may decrease lamotrigine plasma concentrations, potentially leading to loss of seizure control.

• Not available

• Signs and symptoms of venous thromboembolism (VTE) such as leg pain, swelling, warmth, redness; sudden shortness of breath; chest pain.
• Signs and symptoms of stroke such as sudden severe headache, sudden numbness or weakness (especially on one side of the body), sudden vision changes, sudden trouble speaking or understanding speech, sudden dizziness or loss of balance.
• Signs and symptoms of myocardial infarction (MI) such as chest pain or pressure, pain radiating to arm/back/neck/jaw, shortness of breath, sweating, nausea.
• Signs and symptoms of breast cancer such as new lump, skin changes, nipple discharge, nipple inversion.
• Signs and symptoms of liver dysfunction such as jaundice, dark urine, pale stools, abdominal pain, fatigue.
• Signs of angioedema (swelling of face, tongue, throat, difficulty breathing).
• Changes in mood or signs of depression.

Contraindicated. Estrogen therapy is not indicated during pregnancy. There is no evidence that estrogens are effective in preventing threatened or habitual abortion. There is no indication for estrogen therapy during pregnancy, and there is evidence of potential harm to the fetus.

Not recommended. Estrogens are excreted in human milk and may decrease the quantity and quality of breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Safety and effectiveness in pediatric patients have not been established. Divigel is not indicated for use in children.

Women 65 years of age or older may have an increased risk of probable dementia with estrogen-alone therapy, as seen in the WHIMS substudy of the WHI. Use the lowest effective dose for the shortest duration consistent with treatment goals and risks. Close monitoring for adverse events is recommended.

• Divigel is a transdermal gel, which avoids first-pass hepatic metabolism, potentially leading to a more favorable lipid profile and less impact on clotting factors compared to oral estrogens.
• Apply the gel to a clean, dry, intact area of skin on one thigh. Rotate application sites if irritation occurs.
• Allow the gel to dry completely (typically 2-5 minutes) before dressing or coming into contact with others, to prevent transfer.
• Patients with an intact uterus must also take a progestin to reduce the risk of endometrial hyperplasia and cancer associated with unopposed estrogen therapy.
• Regular follow-up appointments are crucial to reassess the need for continued therapy and monitor for adverse effects, especially given the black box warnings.
• Inform patients about the importance of reporting any abnormal vaginal bleeding, leg pain/swelling, chest pain, or sudden neurological symptoms immediately.

• Other hormone therapy regimens (e.g., conjugated estrogens, synthetic estrogens)
• Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine)
• Non-hormonal therapies for vulvar/vaginal atrophy (e.g., vaginal moisturizers, lubricants, ospemifene, prasterone)

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 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 details about the medication taken, the amount, and the time it occurred.