Divigel (Estradiol Gel): Uses, Dosage, Side Effects, Interactions and Other Useful Information (Estradiol)

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Sandrena Gel 0.1% (1mg) Gel

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Divigel (Estradiol Gel) is a topical medication primarily prescribed for women experiencing menopausal symptoms such as hot flashes and vaginal dryness. This clear gel contains estradiol, a form of estrogen that regulates various bodily processes. While Divigel may have additional uses, caution must be exercised due to potential risks associated with uterine cancer and blood clots. When healthcare providers prescribe Divigel, it is important to take into account the patient's medical history and to discuss the potential risks associated with the medication.

Key Takeaways


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Drug Summary and Uses

Divigel is commonly prescribed as a low-dose gel form of estrogen for menopausal women who are experiencing hot flashes and night sweats. The drug is applied topically and administered once daily. It is a clear, colorless gel that contains estradiol, a form of estrogen that regulates various processes in the body. Divigel is specifically used to treat symptoms that include hot flashes, vaginal dryness, burning, and irritation.

However, it is important to note that Divigel may have other uses not listed in the medication guide. Pregnant individuals should not use Divigel, as estradiol, the active ingredient, may increase the risk of uterine cancer. Divigel can also increase the risk of blood clots, stroke, heart attack, and certain cancers. Therefore, individuals with a history of heart attack, stroke, blood clot, liver disease, or bleeding disorders should avoid using Divigel.

It is crucial for individuals to discuss any medical conditions and risk factors with their doctor before using Divigel. Additionally, Divigel should not be used to prevent heart disease, stroke, or dementia. If there is unexplained vaginal bleeding or certain types of cancer, Divigel should not be used. Allergic reactions to estradiol topical are a contraindication for using Divigel. It is important to follow the prescribed dosage and to inform the prescribing doctor about all medicines the patient may be currently taking.

Common Side Effects of Divigel

Moving on to the topic of common side effects associated with the use of Divigel, it is important to be aware of potential adverse reactions that may occur while using this medication. Here is a list of common side effects to watch out for:

  1. Nausea and vomiting: Divigel can sometimes cause gastrointestinal discomfort, leading to nausea and vomiting. If these symptoms persist or become severe, it is important to consult your healthcare provider.

  2. Breast swelling: Divigel may cause breast swelling or tenderness. This is a common side effect and should subside over time. However, if the swelling becomes severe or painful, it is advisable to seek medical attention.

  3. Skin changes: Divigel can cause changes in the skin, such as acne or alterations in skin color. These effects are usually temporary and should improve with continued use. If you experience any concerning or persistent skin changes, consult your doctor.

  4. Reduced appetite: Some individuals may experience a decrease in appetite while using Divigel. If this leads to significant weight loss or affects your overall well-being, it is important to discuss it with your healthcare provider.

It is important to note that not everyone will experience side effects, and some individuals may experience different or additional side effects. If you have any concerns or questions about the side effects of Divigel, it is best to consult with your healthcare provider.

Other Side Effects of Divigel

The occurrence of other side effects associated with the use of Divigel should also be taken into consideration. While Divigel is generally well-tolerated, there are some potential side effects that users should be aware of. These side effects may vary in severity and frequency from person to person.

Some women may experience vaginal pain, dryness, or discomfort while using Divigel. Decreased sex drive and difficulty having an orgasm have also been reported. Swelling, weight gain, and migraine headaches are additional side effects that may occur. In some cases, dizziness and depression have been reported as well. Break-through bleeding may also occur in some women.

It is important to note that these side effects are not common and do not occur in all users of Divigel. However, if any of these side effects persist or worsen, it is important to consult a healthcare professional for further evaluation and guidance.

As with any medication, it is important to weigh the potential benefits against the potential risks and side effects. If you have any concerns or questions about the use of Divigel or its side effects, it is recommended to consult with your healthcare provider for personalized advice and guidance.

Serious Side Effects of Divigel

Serious side effects of Divigel include an increased risk of breast cancer, cancer of the uterus, stroke, heart attack, blood clots, dementia, and gallbladder disease. These side effects should be taken seriously and individuals using Divigel should be aware of the potential risks. It is important to discuss any concerns or symptoms with a healthcare provider. Here are four important points to know about the serious side effects of Divigel:

  1. Increased risk of breast cancer: Divigel has been associated with an increased risk of breast cancer. Regular breast exams and mammograms are recommended for women using Divigel.

  2. Cancer of the uterus: Divigel may also increase the risk of cancer of the uterus. Women who are using Divigel should discuss the potential risks with their healthcare provider.

  3. Stroke and heart attack: Divigel has been linked to an increased risk of stroke and heart attack. Individuals with a history of cardiovascular disease should use Divigel with caution, and should discuss the potential risks with their healthcare provider.

  4. Blood clots: Divigel can increase the risk of blood clots, which can lead to serious complications such as deep vein thrombosis (DVT) or pulmonary embolism. It is important to be aware of the signs and symptoms of blood clots and seek medical attention if any occur.

It is crucial to weigh the benefits and risks of using Divigel with a healthcare provider before starting treatment. Regular monitoring and open communication with a healthcare provider can help ensure the safe use of the drug.

Different Forms of Divigel

Continuing the discussion on the various aspects of Divigel, it is important to note the different forms in which this medication is available. Divigel is primarily available as a low-dose gel form of estrogen, which is applied topically to the skin. The gel is clear and colorless, making it easy to apply. It delivers sustained concentrations of estradiol when used once daily.

Divigel comes in four different doses: 0.25g, 0.5g, 0.75g, and 1.0g. The dosage and administration should be determined based on individual treatment goals and risks. It is important to start with the lowest effective dose and adjust as necessary.

It is worth noting that Divigel is available only as a gel form and does not come in other forms such as lotion or spray. Therefore, patients using Divigel will need to apply the gel topically to the skin as directed by their healthcare provider.

FDA Drug Information for Divigel

The FDA provides important information regarding the use, dosage, side effects, interactions, and other useful details about Divigel (Estradiol Gel). Here are some key points to consider:

  1. Indications & Dosage: Divigel is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause. The dosage and administration should be determined based on individual treatment goals and risks. In general, progestin should be considered when prescribing estrogen for a postmenopausal woman to reduce the risk of endometrial cancer.

  2. Side Effects & Drug Interactions: Common side effects of Divigel include nausea, vomiting, loss of appetite, swollen breasts, and acne or skin color changes. Less common but serious side effects include increased risk of breast cancer, cancer of the uterus, stroke, heart attack, blood clots, dementia, and gallbladder disease. Divigel may interact with certain medications, such as St. John's wort, blood thinners, and antibiotics.

  3. Warnings & Precautions: Divigel should not be used by pregnant women or nursing mothers. Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia. There is an increased risk of endometrial cancer in women using unopposed estrogens. Divigel should not be used if there is unexplained vaginal bleeding or certain types of cancer. The risks and benefits of estrogen therapy should be carefully considered in women with a history of breast cancer, endometrial cancer, or cardiovascular disease.

Description and Dosage of Divigel

Divigel is a clear, colorless gel that delivers sustained concentrations of estradiol when applied once daily to the skin. It is available in four doses of 0.25, 0.5, 0.75, and 1.0 g for topical application. The active component of the gel is estradiol. Divigel is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause. The dosage and administration should be determined based on individual treatment goals and risks. Generally, a progestin should be considered when prescribing estrogen for a otherwise healthy postmenopausal women to reduce the risk of endometrial cancer. It is important to start Divigel at the lowest effective dose. The gel should be applied to clean, dry, unbroken skin and allowed to dry before dressing. The application site should not be washed within one hour of application. Divigel should not be used by pregnant women or nursing mothers. It may interact with certain medications, such as St. John's wort, blood thinners, and antibiotics. It is important to follow the prescribed dosage and consult a healthcare provider for further information.

Indications for Divigel

For menopausal women experiencing moderate to severe vasomotor symptoms, Divigel is indicated as a treatment option. Here are four important indications for Divigel:

  1. Hot Flashes: Divigel is effective in reducing the frequency and severity of hot flashes, which are one of the most common symptoms of menopause. It helps regulate body temperature and relieves sudden waves of heat.

  2. Vaginal Dryness: Divigel can alleviate vaginal dryness, burning, and irritation, which menopausal women often experience. It helps to restore moisture and improve the comfort of intimate activities.

  3. Hormone Replacement Therapy: Divigel is a hormone replacement therapy that can help restore hormonal balance in menopausal women. It provides the body with the necessary estrogen levels that decline during this stage of life.

  4. Quality of Life: Divigel can significantly improve the overall quality of life for menopausal women by reducing bothersome symptoms such as night sweats, mood swings, and sleep disturbances. It helps women to feel more comfortable and in control during this transitional phase.

It is important to consult with a healthcare provider to determine if Divigel is the right treatment option based on individual symptoms and medical history.

Dosage and Administration of Divigel

When considering the appropriate dosage and administration of Divigel, healthcare providers will take into account individual treatment goals and risks associated with hormone replacement therapy. Divigel is available in four doses of 0.25, 0.5, 0.75, and 1.0 g for topical application. The dosage and administration should be determined based on the specific needs of each patient. Generally, the lowest effective dose should be used for the shortest duration necessary to achieve treatment goals. In postmenopausal women, a progestin should be considered along with Divigel to reduce the risk of endometrial cancer. Divigel is applied once daily to clean, dry, unbroken skin. It should not be applied to irritated or red skin. After application, the gel should be allowed to dry before dressing, and the application site should not be washed within one hour. Patients should follow the directions on the prescription label and consult their healthcare provider for any questions or concerns about the proper use of Divigel.

Considerations for Postmenopausal Women

Postmenopausal women should carefully consider the risks and benefits of hormone replacement therapy before using Divigel or any other estrogen therapy. Here are some important considerations for postmenopausal women:

  1. Consult your healthcare provider: It is essential to have an open and honest conversation with your healthcare provider about your medical history, any current health conditions, and your individual treatment goals. They can help determine if hormone replacement therapy is appropriate for you.

  2. Understand the risks: Estrogen therapy, including Divigel, comes with certain risks. These include an increased risk of breast and uterine cancer, stroke, blood clots, and heart disease. It is important to weigh these risks against the potential benefits of symptom relief.

  3. Consider alternative treatments: Hormone replacement therapy is not the only option for managing menopausal symptoms. There are non-hormonal treatments available, such as lifestyle changes, dietary supplements, and alternative therapies. Discuss these options with your healthcare provider to find the most suitable approach for you.

  4. Regular check-ups: If you decide to use hormone replacement therapy, it is crucial to have regular check-ups with your healthcare provider. They can monitor your treatment response, assess any potential side effects, and make any necessary adjustments to your regimen.

Warnings and Precautions for Divigel

Before using Divigel, it is important to be aware of the warnings and precautions associated with this medication. Divigel is a prescription gel form of estrogen used to treat certain symptoms of menopause, such as hot flashes and vaginal dryness. However, there are several important considerations to keep in mind before starting treatment with Divigel.

Firstly, Divigel should not be used by pregnant women or nursing mothers, as it may pass into breast milk or otherwise harm the baby. Additionally, individuals with a history of certain medical conditions, including heart disease, stroke, blood clots, liver or kidney disease, or bleeding disorders, should avoid using Divigel. It is also important to note that Divigel should not be used to prevent heart disease, stroke, or dementia.

Furthermore, Divigel can increase the risk of blood clots, stroke, heart attack, and certain cancers. It is important to discuss any personal or family history of these conditions with a healthcare provider before starting treatment. Additionally, Divigel should not be used if there is unexplained vaginal bleeding or certain types of cancer.

Risks of Estrogen-alone Therapy

Although estrogen-alone therapy has its benefits, it is important to consider the potential risks associated with its use. Estrogen therapy has been linked to several serious health risks, including:

  1. Increased risk of endometrial cancer: Estrogen-alone therapy without the use of progestin has been found to increase the risk of endometrial cancer in women. It is crucial to carefully evaluate the individual's risk factors before initiating estrogen therapy.

  2. Cardiovascular disease: Estrogen-alone therapy should not be used for the prevention of cardiovascular disease. Studies have shown (Study 1, Study 2) an increased risk of stroke, heart attack, and blood clots in women using estrogen therapy.

  3. Dementia: Estrogen-alone therapy has not been proven to prevent or treat dementia. In fact, some studies (Study) suggest that it may increase the risk of cognitive decline and dementia in older women.

  4. Breast cancer: Although the evidence is inconclusive, some studies (Study) have suggested a slight increase in the risk of breast cancer with long-term use of estrogen therapy.

It is important to weigh the benefits against the potential risks when considering estrogen-alone therapy. Women with a history of breast cancer, endometrial cancer, or cardiovascular disease may need to explore alternative treatment options. It is essential to consult with a healthcare professional to make an informed decision about estrogen-only therapy.

Risks of Estrogen Plus Progestin Therapy()

Continuing the discussion on the risks of estrogen therapy, it is important to address the potential dangers associated with estrogen plus progestin therapy. Estrogen plus progestin therapy is commonly prescribed to postmenopausal women with a uterus to reduce the risk of endometrial cancer. However, it is essential to note that this therapy is associated with increased risks of deep vein thrombosis (DVT), pulmonary embolism, stroke, myocardial infarction, and invasive breast cancer.

Women considering estrogen plus progestin therapy should carefully weigh the risks and benefits, especially if they have a history of breast cancer, endometrial cancer, or cardiovascular disease. It is crucial to have an open and honest discussion with their healthcare provider to determine the most suitable treatment option.

Additionally, it is vital to note that Divigel, a form of estradiol gel, should not be used by pregnant women or nursing mothers. It may also interact with certain medications, such as St. John's wort, blood thinners, and antibiotics. Therefore, it is crucial to inform healthcare providers about all medicines being used to ensure the safety and effectiveness of the treatment.

Understanding the potential risks associated with estrogen plus progestin therapy is essential for making informed decisions about menopausal hormone therapy. Women should consult with their healthcare provider to assess their individual risks and determine the most appropriate treatment plan.

Divigel and Pregnancy/Nursing

Addressing the implications of Divigel use during pregnancy and nursing is crucial for ensuring the safety and well-being of both the mother and child. Here are a few important points to consider:

  1. Pregnancy: Divigel should not be used by pregnant women. Estrogen medications, including Divigel, may increase the risk of birth defects in the developing fetus. It is important to discuss alternative treatment options with a healthcare provider if pregnancy is planned or suspected.

  2. Breastfeeding: Divigel should not be used by nursing mothers. Estrogen can pass into breast milk and may harm the nursing infant. It is recommended to avoid Divigel while breastfeeding and consult with a healthcare provider for suitable alternatives.

  3. Safety concerns: Divigel is not intended for use in children. It is important to keep Divigel out of reach of children to avoid accidental exposure, as it may cause side effects in children.

  4. Alternative options: If pregnancy or breastfeeding is a concern, healthcare providers can suggest alternative treatments for managing menopausal symptoms. Non-hormonal therapies, lifestyle modifications, and other medications may be considered as safer options.

It is crucial to consult with a healthcare provider before using Divigel or any other medication during pregnancy or while breastfeeding to ensure the health and well-being of both mother and child.

Interactions With Other Medications

Divigel may interact with other medications, including prescription and over-the-counter drugs, as well as herbal supplements and vitamins. It is important to inform all healthcare providers about all medicines being used to avoid potential interactions. Certain medications may affect the way Divigel works, or Divigel may affect the effectiveness of other medications. For example, medications that increase the activity of liver enzymes, such as St. John's wort, phenobarbital, carbamazepine, and rifampin, may reduce the levels of estrogen in the body, potentially decreasing the therapeutic effects of Divigel. On the other hand, medications that inhibit the activity of liver enzymes, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice, may increase estrogen levels in the body, potentially increasing the risk of side effects. It is important to discuss all current medications, including vitamins and herbal supplements, with a healthcare provider before starting Divigel to ensure safe and effective use of the medication.

Side Effects of Divigel and Drug Interactions

1.          Moving on to the potential side effects and interactions of Divigel, it is important to be aware of the possible adverse reactions and drug interactions that may occur with this medication. Here are some key points to consider:

  • Common side effects of Divigel include nausea, vomiting, loss of appetite, swollen breasts, and acne or skin color changes.

  • Other side effects that may occur include vaginal pain, dryness, or discomfort, decreased sex drive, difficulty having an orgasm, swelling, weight gain, migraine headaches, dizziness, depression, and breakthrough bleeding.

  • Less common but serious side effects of Divigel include breast cancer, cancer of the uterus, stroke, heart attack, blood clots, dementia, and gallbladder disease.

  • Divigel may interact with certain medications, such as St. John's wort, blood thinners, and antibiotics. It is important to inform all healthcare providers about all medicines being used.

It is crucial to be aware of these potential side effects and drug interactions to ensure the safe and effective use of Divigel. However, it is also important to note that the adverse reaction rates observed in clinical trials may not reflect the rates observed in practice. In the subsequent section, we will discuss the serious adverse reactions of Divigel.

Serious Adverse Reactions of Divigel

Serious adverse reactions can occur with the use of Divigel, a topical gel containing estradiol. These reactions include breast and ovarian cancer,, cancer of the uterus, stroke, heart attack, blood clots, dementia, and gallbladder disease. It is important to be aware of these potential risks when considering the use of Divigel. While Divigel is an effective treatment for menopausal symptoms such as hot flashes and vaginal dryness, it is essential to understand the potential serious adverse reactions associated with its use.

Breast cancer and cancer of the uterus are two significant risks associated with Divigel. It is crucial to discuss these risks with your healthcare provider and undergo regular breast and gynecological examinations while using Divigel. Additionally, stroke, heart attack, and blood clots are potential serious adverse reactions that may occur. These conditions can be life-threatening and require immediate medical attention.

Dementia and gallbladder disease are also important risks to consider. Divigel use has been associated with an increased risk of dementia, particularly in women over the age of 65. Gallbladder disease, including gallstones, is another potential adverse reaction that may occur with Divigel use.

It is essential to weigh the potential benefits of Divigel against these serious adverse reactions. Discussing your individual risks and treatment goals with your healthcare provider is crucial in making an informed decision about the use of Divigel.

Adverse Events Observed in Clinical Trials

During clinical trials, several adverse events were observed with the use of Divigel (estradiol gel). These adverse events include:

  1. Nasopharyngitis: This is a common adverse event observed in clinical trials, characterized by inflammation of the nasal passages and the back of the throat. It may present with symptoms such as a runny or stuffy nose, sore throat, and sneezing.

  2. Upper respiratory tract infection: Another common adverse event reported in clinical trials, upper respiratory tract infection refers to infections affecting the nose, sinuses, throat, and larynx. Symptoms may include nasal congestion, cough, sore throat, and fever.

  3. Vaginal mycosis: This adverse event refers to a fungal infection of the vagina, commonly known as a yeast infection. Symptoms may include itching, burning, and abnormal vaginal discharge.

  4. Breast tenderness: Some women may experience breast tenderness as an adverse event while using Divigel. This can cause discomfort or pain in the breasts.

It is important to note that the occurrence of these adverse events may vary from person to person, and not all individuals will experience them. If you have any concerns or experience any adverse events while using Divigel, it is recommended to consult your healthcare provider for guidance and support.

Additional Adverse Reactions Reported

In addition to the adverse events observed in clinical trials, there have been reports of other adverse reactions associated with the use of Divigel (estradiol gel). While the most common adverse events observed in placebo-controlled studies included nasopharyngitis, upper respiratory tract infection, vaginal mycosis, breast tenderness, and metrorrhagia, additional adverse reactions have been reported during post-approval use. These include arthralgia, application site rash, asthenia, chest pain and discomfort, fatigue, and weight increased.

It is important to note that the rates of these adverse reactions observed in clinical trials may not reflect the rates observed in practice. Therefore, healthcare providers should be vigilant in monitoring patients for any signs of adverse reactions and promptly address them.

Furthermore, it is worth mentioning that no drug-drug interaction studies have been conducted for Divigel. However, it is known that estrogens, such as those in Divigel, are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers of CYP3A4, such as St. John's wort, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of estrogens. Conversely, inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice, may increase plasma concentrations of estrogens. These changes in drug metabolism may result in a decrease in therapeutic effects or side effects.

Drug-Drug Interaction Studies for Divigel

Drug-drug interaction studies have been conducted to evaluate the potential interactions of Divigel (estradiol gel) with other medications. Here are four important findings from these studies:

  1. Increased risk of blood clotting: Divigel may interact with certain medications, such as blood thinners (e.g., warfarin), increasing the risk of blood clots. It is important to inform your healthcare provider if you are taking any blood-thinning medications while using Divigel.

  2. Decreased effectiveness of Divigel: Some medications, such as St. John's wort, phenobarbital, carbamazepine, and rifampin, can reduce the effectiveness of Divigel by decreasing its plasma concentrations. If you take any of these medications, your healthcare provider may need to adjust your Divigel dosage or consider alternative treatment options.

    Increased plasma concentrations of Divigel: On the other hand, medications like erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice can increase the plasma concentrations of Divigel. This can lead to an increased risk of side effects. Your healthcare provider may need to monitor you more closely if you are taking any of these medications while using Divigel.

  3. Changes in drug metabolism: Estrogens, including the active component of Divigel, are partially metabolized by an enzyme called cytochrome P450 3A4 (CYP3A4). Medications that inhibit or induce CYP3A4, such as certain antibiotics and antifungal agents, can affect the metabolism of Divigel. This may result in a decrease in therapeutic effects or an increase in side effects.

It is crucial to inform your healthcare provider about all the medications you are taking, including prescription, over-the-counter, and herbal products, to avoid any potential drug interactions with Divigel. Your healthcare provider can then make appropriate adjustments to your treatment plan to ensure your safety and well-being.

Metabolism of Estrogens by CYP3A4

As estrogens, including the active component of Divigel, are metabolized in part by the enzyme cytochrome P450 3A4 (CYP3A4), medications that inhibit or induce CYP3A4 can affect the metabolism of Divigel, potentially altering its therapeutic effects or increasing the risk of side effects. CYP3A4 is an important enzyme in the liver that plays a crucial role in the breakdown of many drugs, including estrogens. Inhibition of CYP3A4 can result in increased levels of Divigel in the body, leading to an enhanced therapeutic effect or an increased risk of side effects. On the other hand, induction of CYP3A4 can lead to decreased levels of Divigel, potentially reducing its effectiveness. Medications that are known to inhibit CYP3A4 include certain antibiotics, antifungals, and HIV protease inhibitors. Conversely, drugs that induce CYP3A4 include certain anticonvulsants, rifampin, and St. John's wort. It is important for healthcare providers to be aware of these potential interactions when prescribing Divigel, and to adjust the dosage or monitor patients closely if necessary.

Inducers and Inhibitors of CYP3A4

Certain medications can either increase or decrease the activity of the enzyme CYP3A4, which plays a significant role in the metabolism of Divigel and other estrogens. Understanding the impact of these medications is important in order to optimize the therapeutic effects and minimize potential side effects of Divigel. Here are four key points to consider regarding inducers and inhibitors of CYP3A4:

  1. Inducers of CYP3A4: Medications such as St. Johns wort, phenobarbital, carbamazepine, and rifampin can increase the activity of CYP3A4. This may lead to a decrease in plasma concentrations of estrogens, potentially reducing the therapeutic effects of Divigel.

  2. Inhibitors of CYP3A4: On the other hand, medications like erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice can inhibit the activity of CYP3A4. This can result in increased plasma concentrations of estrogens, potentially increasing the risk of side effects associated with Divigel.

  3. Changes in drug metabolism: These inducers and inhibitors can alter the metabolism of Divigel, affecting its efficacy and safety profile. It is important to consider these interactions when prescribing Divigel or when initiating or discontinuing any medications that may impact CYP3A4 activity.

  4. Effects on therapeutic outcomes: The changes in drug metabolism caused by inducers and inhibitors of CYP3A4 may result in a decrease or increase in the therapeutic effects or side effects of Divigel. Close monitoring of patients and adjustments in dosage may be necessary to ensure optimal treatment outcomes.

Understanding the role of inducers and inhibitors of CYP3A4 in the metabolism of Divigel is crucial for healthcare providers to make informed decisions regarding treatment options and to ensure the safe and effective use of this medication. With this knowledge, we can now explore how changes in drug metabolism and effects can impact the use of Divigel.

Changes in Drug Metabolism and Effects

Changes in drug metabolism and effects can significantly impact the use of Divigel, an estradiol gel, by altering its therapeutic efficacy and safety profile. Divigel contains estradiol, which is metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, drugs that induce or inhibit CYP3A4 may affect the metabolism of Divigel and subsequently its effects.

Inducers of CYP3A4, such as St. John's wort, phenobarbital, carbamazepine, and rifampin, can reduce the plasma concentrations of estrogens. This can lead to a decrease in the therapeutic effects of Divigel and potentially compromise its efficacy. On the other hand, inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice, can increase the plasma concentrations of estrogens. This can result in an increase in therapeutic effects and potentially lead to an increased risk of side effects.

It is important for healthcare providers to be aware of these potential drug interactions when prescribing Divigel to ensure the optimal therapeutic outcomes for patients. Monitoring for any changes in therapeutic effects or side effects is crucial, especially when Divigel is co-administered with drugs that induce or inhibit CYP3A4. Adjustments to the dosage or treatment plan may be necessary to maintain the desired therapeutic efficacy and safety of Divigel.

Warnings, Precautions, and Related Drugs

The use of Divigel (Estradiol Gel) requires careful consideration of warnings, precautions, and related drugs. It is important to be aware of certain warnings before using Divigel. Pregnant individuals should not use Divigel as it may harm the unborn baby. Divigel contains estradiol, which may increase the risk of uterine cancer. It is also important to note that Divigel can increase the risk of blood clots, stroke, heart attack, and certain cancers. Contact with Divigel can cause side effects in a child, so it is important to keep it out of their reach. Divigel should not be used to prevent heart disease, stroke, or dementia. It is contraindicated in cases of unexplained vaginal bleeding or certain types of cancer. Individuals with a history of heart attack, stroke, blood clot, liver disease, or bleeding disorder should avoid using Divigel. Allergic reactions to estradiol topical are also a contraindication. Before using Divigel, it is important to discuss any medical conditions or risk factors with a healthcare provider. It is also important to be aware of related drugs such as Estradiol, Premarin, Estrace, Prempro, and ethinyl estradiol/norethindrone, as they may have similar uses or contain similar active ingredients. Always follow the prescribed medication and dosage, and inform all healthcare providers about all medicines being used.

Frequently Asked Questions

Can Divigel Be Used to Prevent Cardiovascular Disease or Dementia?

No, Divigel should not be used to prevent cardiovascular disease or dementia. It is important to discuss the risks and benefits of estrogen therapy with a healthcare provider before using Divigel for any specific medical condition.

What Are the Risks and Benefits of Using Divigel in Women With a History of Breast Cancer, Endometrial Cancer, or Cardiovascular Disease?

The risks and benefits of using Divigel in women with a history of breast cancer, endometrial cancer, or cardiovascular disease should be carefully considered. Divigel is associated with potential risks such as increased risk of breast and reported endometrial cancer risk and cardiovascular events.

Are There Any Specific Medical Conditions or Risk Factors That Should Be Discussed With a Doctor Before Using Divigel?

Certain medical conditions, such as a history of breast cancer, breast or endometrial cancer, or cardiovascular disease, should be discussed with a doctor before using Divigel. It is important to assess the risks and benefits of the medication in these cases.

How Should Divigel Be Applied and What Precautions Should Be Taken?

Divigel should be applied as directed by a healthcare professional to clean, dry, unbroken skin. Precautions include avoiding application to irritated or red skin and allowing the gel to dry before dressing.

Can Divigel Interact With Other Medications, Including Over-The-Counter Medicines, Vitamins, and Herbal Products?

Yes, Divigel can interact with other medications, including over-the-counter medicines, vitamins, and herbal products. It is important to inform all healthcare providers about all medicines being used to avoid potential interactions and ensure safe and effective use of Divigel.

Estradiol Information

Estrogen (ess' troe jen) Amnestrogen® (esterified estrogens)¶ Cenestin® (conjugated synthetic A estrogens) Enjuvia® (conjugated synthetic B estrogens) Estrace® Tablets (estradiol) Estratab® (esterified estrogens) Evex® (esterified estrogens)¶ Femogen® (esterified estrogens)¶ Menest® (esterified estrogens) Ogen® Tablets (estropipate) Ortho-est® (estropipate) Premarin® Tablets (conjugated estrogens) Covaryx® (as a combination product containing Esterified Estrogens, Methyltestosterone) Essian® (as a combination product containing Esterified Estrogens, Methyltestosterone) Estratest® (as a combination product containing Esterified Estrogens, Methyltestosterone) Femtest® (as a combination product containing Esterified Estrogens, Methyltestosterone) Menogen® (as a combination product containing Esterified Estrogens, Methyltestosterone) Menrium® (as a combination product containing Chlordiazepoxide, Esterified Estrogens)¶ Milprem® (as a combination product containing Conjugated Estrogens, Meprobamate)¶ PMB® (as a combination product containing Conjugated Estrogens, Meprobamate)¶ Premarin® with Methyltestosterone (as a combination product containing Conjugated Estrogens, Methyltestosterone) Syntest® (as a combination product containing Esterified Estrogens, Methyltestosterone) conjugated estrogens esterified estrogens estradiol estropipate Estrogen increases the risk that you will develop endometrial cancer (cancer of the lining of the uterus [womb]). The longer you take estrogen, the greater the risk that you will develop endometrial cancer. If you have not had a hysterectomy (surgery to remove the uterus), you should be given another medication called a progestin to take with estrogen. This may decrease your risk of developing endometrial cancer, but may increase your risk of developing certain other health problems, including breast cancer. Before you begin taking estrogen, tell your doctor if you have or have ever had cancer and if you have unusual vaginal bleeding. Call your doctor immediately if you have abnormal or unusual vaginal bleeding during your treatment with estrogen. Your doctor will watch you closely to help ensure you do not develop endometrial cancer during or after your treatment. In a large study, women who took estrogen with progestins had a higher risk of heart attacks, strokes, blood clots in the lungs or legs, breast cancer, and dementia (loss of ability to think, learn, and understand). Women who take estrogen alone may also have a higher risk of developing these conditions. Tell your doctor if you smoke or use tobacco, if you have had a heart attack or a stroke in the past year, and if you or anyone in your family has or has ever had blood clots or breast cancer. Also tell your doctor if you have or have ever had high blood pressure, high blood levels of cholesterol or fats, diabetes, heart disease, lupus (a condition in which the body attacks its own tissues causing damage and swelling), breast lumps, or an abnormal mammogram (x-ray of the breast used to find breast cancer). The following symptoms can be signs of the serious health conditions listed above. Call your doctor immediately if you experience any of the following symptoms while you are taking estrogen: sudden, severe headache; sudden, severe vomiting; speech problems; dizziness or faintness; sudden complete or partial loss of vision;double vision; weakness or numbness of an arm or a leg; crushing chest pain or chest heaviness; coughing up blood; sudden shortness of breath; difficulty thinking clearly, remembering, or learning new things; breast lumps or other breast changes; discharge from nipples; or pain, tenderness, or redness in one leg. You can take steps to decrease the risk that you will develop a serious health problem while you are taking estrogen. Do not take estrogen alone or with a progestin to prevent heart disease, heart attacks, strokes, or dementia. Take the lowest dose of estrogen that controls your symptoms and only take estrogen as long as needed. Talk to your doctor every 3 to 6 months to decide if you should take a lower dose of estrogen or should stop taking the medication. You should examine your breasts every month and have a mammogram and a breast exam performed by a doctor every year to help detect breast cancer as early as possible. Your doctor will tell you how to properly examine your breasts and whether you should have these exams more often than once a year because of your personal or family medical history. Tell your doctor if you are having surgery or will be on bed rest. Your doctor may tell you to stop taking estrogen 4 to 6 weeks before the surgery or bed rest to decrease the risk that you will develop blood clots. Talk to your doctor regularly about the risks and benefits of taking estrogen.

Estrogen is used to treat hot flushes ('hot flashes'; sudden strong feelings of heat and sweating) in women who are experiencing menopause ('change of life', the end of monthly menstrual periods). Some brands of estrogen are also used to treat vaginal dryness, itching, or burning, or to prevent osteoporosis (a condition in which the bones become thin and weak and break easily) in women who are experiencing or have experienced menopause. However, women who need a medication only to treat vaginal dryness or only to prevent osteoporosis should consider a different treatment. Some brands of estrogen are also to relieve symptoms of low estrogen in young women who do not produce enough estrogen naturally. Some brands of estrogen are also used to relieve the symptoms of certain types of breast and prostate (a male reproductive gland) cancer. Estrogen is in a class of medications called hormones. It works by replacing estrogen that is normally produced by the body.

Estrogen comes as a tablet to take by mouth. It is usually taken with or without food once a day. Estrogen is sometimes taken every day and sometimes taken according to a rotating schedule that alternates a period of time when estrogen is taken every day with a period of time when estrogen is not taken. When estrogen is used to relieve the symptoms of cancer, it is usually taken three times a day. Take estrogen at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take estrogen exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Your doctor may start you on a low dose of estrogen and gradually increase your dose if your symptoms are still bothersome, or decrease your dose if your symptoms are well-controlled. Talk to your doctor about how well estrogen works for you. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Before taking estrogen, tell your doctor and pharmacist if you are allergic to any brand of oral estrogen, any other estrogen products, any other medications, or any of the ingredients in estrogen tablets. If you will be taking Estrace® brand tablets, tell your doctor and pharmacist if you are allergic to aspirin or tartrazine (a food color additive). Ask your pharmacist or check the manufacturer's patient information for a list of the inactive ingredients in the brand of estrogen tablets you plan to take. tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: amiodarone (Cordarone, Pacerone); certain antifungals such as itraconazole (Sporanox) and ketoconazole (Nizoral); aprepitant (Emend); carbamazepine (Carbatrol, Epitol, Tegretol); cimetidine (Tagamet); clarithromycin (Biaxin); cyclosporine (Neoral, Sandimmune); dexamethasone (Decadron, Dexpak); diltiazem (Cardizem, Dilacor, Tiazac, others); erythromycin (E.E.S, Erythrocin);fluoxetine (Prozac, Sarafem); fluvoxamine (Luvox); griseofulvin (Fulvicin, Grifulvin, Gris-PEG); lovastatin (Altocor, Mevacor); medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir, in Kaletra), and saquinavir (Fortovase, Invirase); medications for thyroid disease; nefazodone; phenobarbital; phenytoin (Dilantin, Phenytek); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane, in Rifamate); sertraline (Zoloft); troleandomycin (TAO); verapamil (Calan, Covera, Isoptin, Verelan); and zafirlukast (Accolate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor what herbal products you are taking, especially St. John's wort. tell your doctor if you have or have ever had yellowing of the skin or eyes during pregnancy or during your treatment with an estrogen product, endometriosis (a condition in which the type of tissue that lines the uterus [womb] grows in other areas of the body), uterine fibroids (growths in the uterus that are not cancer), asthma, migraine headaches, seizures, porphyria (condition in which abnormal substances build up in the blood and cause problems with the skin or nervous system), very high or very low levels of calcium in your blood, or thyroid, liver, kidney, gallbladder, or pancreatic disease. tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking estrogen, call your doctor immediately. talk to your doctor about the risks and benefits of taking estrogen if you are 65 years of age or older. Older women should not usually take oral estrogen unless they are also taking other hormones. Oral estrogen taken without other hormones is not as safe or effective as other medications that can be used to treat the same condition. if you are taking estrogen to prevent osteoporosis, talk to your doctor about other ways to prevent the disease such as exercising and taking vitamin D and/or calcium supplements.

Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medicine. Talk to your doctor about ways to increase the amount of calcium and vitamin D in your diet, especially if you are taking estrogen to prevent osteoporosis.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Estrogen may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: breast pain or tenderness upset stomach vomiting heartburn constipation diarrhea gas weight gain or loss leg cramps nervousness depression dizziness burning or tingling in the arms or legs tight muscles hair loss unwanted hair growth spotty darkening of the skin on the face difficulty wearing contact lenses swelling, redness, burning, itching, or irritation of the vagina vaginal discharge change in sexual desire cold symptoms Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately: bulging eyes sore throat, fever, chills, cough, and other signs of infection pain, swelling, or tenderness in the stomach loss of appetite weakness yellowing of the skin or eyes joint pain movements that are difficult to control rash or blisters hives itching swelling of the eyes, face, tongue, throat, hands, arms, feet, ankles, or lower legs hoarseness difficulty breathing or swallowing Estrogen may increase your risk of developing cancer of the ovaries or gallbladder disease that may need to be treated with surgery. Talk to your doctor about the risks of taking estrogen. Estrogen may cause growth to slow or stop early in children who take large doses for a long time. Estrogen may also affect the timing and speed of sexual development in children. Your child's doctor will monitor him or her carefully during his or her treatment with estrogen. Talk to your child's doctor about the risks of giving this medication to your child. Estrogen may cause other side effects. Call your doctor if you have any unusual problems while taking this medication. If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

Keep all appointments with your doctor. Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking estrogen. Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription. It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies. ¶ This branded product is no longer on the market. Generic alternatives may be available.

The content on this page is for informational and educational purposes only and does not constitute professional medical advice. Patients should not use the information presented on this page for diagnosing a health-related issue or disease. Before taking any medication or supplements, patients should always consult a physician or qualified healthcare professional for medical advice or information about whether a drug is safe, appropriate or effective.