Vivelle-Dot (estradiol)

How does Vivelle-Dot work?

Estrogens are responsible for many functions in the human body, mainly for the development of the female reproductive system and secondary sex characteristics. Estradiol is the principal intracellular estrogen and is much more potent than its metabolites (estrone and estriol). Estradiol is the primary estrogen secreted before menopause, while estrone and estrone sulfate are more highly produced after menopause.

Estrogens modulate the pituitary secretion of gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) through a negative feedback loop. Estrogens act to reduce the elevated levels of these hormones in postmenopausal women.

Dosage and How to Use

Vivelle-Dot transdermal system is available in the following dosage strengths:

• 0.025 mg/day
• 0.0375 mg/day
• 0.05 mg/day
• 0.075 mg/day
• 0.1 mg/day

When estrogen is prescribed for postmenopausal women with a uterus, consider the addition of a progestogen to reduce the risk of endometrial cancer. Women without a uterus generally do not need a progestogen in combination with estrogen therapy.

Estrogen should be used alone or in combination with a progestogen at the lowest effective dose and shortest duration that reaches treatment goals. Reevaluate postmenopausal women periodically to determine if treatment is still necessary.

Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause or Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause 

Start therapy with Vivelle-Dot 0.0375 mg daily, applied to the skin twice weekly, then make dosage adjustments based on the clinical response. Attempt to taper or discontinue Vivelle-Dot therapy at 3 to 6-month intervals.

Start Vivelle-Dot immediately in women not currently taking oral estrogens or switching from another transdermal estradiol therapy. In women currently taking oral estrogens, start Vivelle-Dot 1 week after stopping oral hormone therapy or sooner if menopausal symptoms reappear.

Vivelle-Dot should be given continuously in women without an intact uterus. In women with an intact uterus, Vivelle-Dot should be given on a cyclic schedule (for example, 3 weeks on Vivelle-Dot followed by 1 week off Vivelle-Dot).

Hypoestrogenism or Prevention of Postmenopausal Osteoporosis

Start therapy with Vivelle-Dot 0.025 mg daily, applied to the skin twice weekly.

Start Vivelle-Dot immediately in women not currently taking oral estrogens or switching from another transdermal estradiol therapy. In women currently taking oral estrogens, start Vivelle-Dot 1 week after stopping oral hormone therapy or sooner if menopausal symptoms reappear.

Vivelle-Dot should be given continuously in women without an intact uterus. In women with an intact uterus, Vivelle-Dot should be given on a cyclic schedule (for example, 3 weeks on Vivelle-Dot followed by 1 week off Vivelle-Dot).

Application instructions

Place the adhesive side on a clean and dry area of the trunk of the body (abdomen or buttocks). Do not apply Vivelle-Dot to the breasts.

Replace Vivelle-Dot twice weekly and rotate the sites of the application. Allow at least one week before reusing a particular site. Avoid application on damaged skin, oily areas, or the waistline (clothing may rub the patch off). Apply the patch immediately after opening and removing the protective liner. Press the patch firmly with the palm for 10 seconds, ensuring good contact.

If the system falls off

Reapply the same patch or apply a new patch to another location. Continue the original treatment schedule. If a woman has forgotten to apply Vivelle-Dot, she should apply the system as soon as possible. Apply the following system according to the original treatment schedule.

Storage

Store in the pouch at 20 to 25°C (68 to 77°F). Excursions permitted between 15 to 30°C (59 to 86°F).

There is still active hormone in the patch after use. After use, fold the sticky sides of the patch together, place it in a child-proof container, then put it in the trash. Do not discard in the toilet.

Overdosage

Estrogen overdosage may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness, and withdrawal bleeding (in women). If overdosage occurs, discontinue Vivelle-Dot therapy and contact your doctor.

Side Effects

The most common side effects of Vivelle-Dot are:

• Headache
• Breast pain
• Irregular vaginal bleeding or spotting
• Painful periods
• Stomach or abdominal cramps
• Bloating
• Nausea and vomiting
• Hair loss
• Fluid retention
• Vaginal yeast infection
• Redness at the patch placement site

Rare but more serious side effects of Vivelle-Dot may be:

• Heart attack
• Stroke
• Blood clots
• Breast cancer, cancer of the lining of the uterus (womb), cancer of the ovary, cancer changes of endometriosis
• Dementia
• High or low blood calcium
• Gallbladder disease
• Visual abnormalities
• High blood pressure
• High levels of fat in your blood
• Liver problems
• Changes in your thyroid hormone levels
• Fluid retention
• Cancer changes of endometriosis
• Enlargement of benign tumors of the uterus
• Worsening of swelling of the face and tongue (angioedema) in women with a history of angioedema

Contact your doctor immediately if you notice one of the following warning signs or other warning signs that raise concern:

• new breast lumps
• unusual vaginal bleeding
• changes in vision or speech
• sudden new severe headaches
• severe pains in your chest or legs with or without shortness of breath and fatigue
• swelling of face and tongue with or without red, itchy bumps

This is not a comprehensive list of all possible side effects. Contact your doctor or pharmacist for more information.

Warnings & Precautions

 Boxed Warnings

• Estrogen-Alone Therapy

  • There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens.
  • The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT).
  • The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years and older.
  • Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.

• Estrogen Plus Progestin Therapy

  • The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke, and myocardial infarction (MI).
  • The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer.
  • The WHIMS estrogen plus progestin ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years and older.
  • Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.

Other warnings

• Gallbladder disease
• Hypercalcemia
• Visual abnormalities
• Addition of Progestogen when a woman has not had a hysterectomy
• Elevated blood pressure
• Exacerbation of hypertriglyceridemia
• Hepatic Impairment or Past History of Cholestatic Jaundice
• Exacerbation of Hypothyroidism
• Fluid retention
• Hypocalcemia
• Exacerbation of endometriosis
• Severe anaphylactic reactions and angioedema
• Exacerbation of other conditions
• Laboratory tests
• Drug-Laboratory Test Interactions

Drug Interactions and Other Interactions

Studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.

CYP3A4 inducers (e.g., St. John’s Wort and carbamazepine) may reduce plasma concentrations of estrogens.

CYP3A4 inhibitors (e.g., clarithromycin and ketoconazole) may increase plasma concentrations of estrogens.

Contraindications

Vivelle-Dot is contraindicated in patients with any of the following:

• Undiagnosed abnormal genital bleeding
• Breast cancer or a history of breast cancer
• Estrogen-dependent neoplasia
• Active DVT, PE, or a history of these conditions
• Active arterial thromboembolic disease (e.g., stroke and MI) or a history of these conditions
• Known anaphylactic reaction, angioedema, or hypersensitivity to Vivelle-Dot
• Hepatic impairment or disease
• Protein C, protein S, antithrombin deficiency, or other known thrombophilic disorders