Activella

The active ingredients in Activella are norethindrone and estradiol. Since Activella is a combination medicine, it works in two specific ways. It works as if they are natural hormones in your body to balance the change in hormones that your body goes through during menopause.

Estradiol is used to replace estrogen. Estradiol, therefore, lowers the symptoms that accompany having low estrogen. These symptoms include night sweats, vaginal irritation/ dryness, and hot flashes. Estradiol will also help improve bone mineral density (BMD) and help prevent overall bone loss. Speak to your doctor about your BMD; having a high BMD means that your bones are stronger and are less likely to fracture.

Norethindrone is a progestin and acts like a progesterone that works by balancing the effects of estrogen to help with the growth of the lining in the uterus.

Follow all directions given to you by your doctor and read all documents provided, including the full Prescribing Information, FDA-Approved Product Labeling, Instructions for Use, and Medication Guide before using Activella. However, the following is a synopsis of the general guidelines for the use of Activella:

• Activella is typically taken once daily, with or without food
• It is important to take the medication at the same time each day to maintain consistent hormone levels in your body
• If you miss a dose, take it as soon as you remember, but do not take two doses at once.
• Regular check-ups with your healthcare provider are essential to monitor your response to Activella and make any necessary adjustments to your treatment plan
• Your doctor may also recommend periodic mammograms and gynecological examinations to ensure your ongoing health and well-being

The most common side effects of Activella seen in clinical trials as compared to placebo include:

• Headache
• Call your doctor if you develop a severe headache, such as a migraine.
• Hair loss
• Back pain
• Nausea or upset stomach
• Trouble sleeping
• Fibroids
• This could become serious. Speak to your healthcare professional if you experience symptoms.
• Breast tenderness
• Weight gain
• Unusual vaginal bleeding
• Breakthrough bleeding
• Bloating
• Common cold symptoms
• Cramps
• Enlarged breasts
• Trouble wearing contact lenses

Some individuals may experience serious side effects while using Activella. These side effects may require immediate medical attention. If you experience any of the following, contact your healthcare provider or seek emergency medical help:

• Stroke, heart attack, and blood clots
• Speak to your doctor about any family history of high blood pressure, high cholesterol, tobacco use, obesity, or blood clots.
• Activella can increase your risk of blood clots. These blood clots have the potential to travel through your body, which could create deep vein thrombosis, or DVT in your legs and arms, or a pulmonary embolism, or PE in your lungs.
• Allergic reaction (could be severe)
• See your doctor immediately if you experience any signs of a severe allergic reaction, including:
• Fainting
• Hives
• Rash
• Tongue swelling
• Shortness of breath
• Breast cancer
• Regularly check your breasts for any changes, and let your doctor know if you observe any abnormal shifts in your breast shape, color, or size. Talk to your healthcare professional about receiving regular mammograms to ensure your breast health.
• Endometrial and uterine cancer
• Endometrial growth happens when the lining in the uterus thickens. Uncontrolled growth can result in endometrial and uterine cancer.
• Be aware of signs of endometrial cancer, including abnormal vaginal bleeding. Talk to your healthcare provider for additional information about warning signs or if you experience any warning signs.
• Ovarian cancers
• Dementia
• Liver or gallbladder problems, including gallbladder disease
• Vision problems
• Changes in the calcium levels in your blood
• Low thyroid hormone levels
• High triglyceride (fat) levels
• Fluid retention (buildup of fluids in your body)
• Pancreatitis

These are not all of the possible side effects of Activella. You should always seek medical advice from your healthcare provider for any questions or concerns about your medical condition or treatment. Read all patient information, medication guides, or drug information sheets that come with this medication. You can also report adverse effects to the Food and Drug Administration at www.fda.gov/medwatch or 1-800-FDA-1088.

Before starting Activella, it is crucial to discuss any existing health conditions with your healthcare provider. You should be sure that your healthcare provider is aware of all your medical conditions, including if you have:

• Known anaphylactic reaction, angioedema, or hypersensitivity to Activella
• Jaundice, or a history of jaundice
• High blood pressure
• Abnormal, undiagnosed vaginal bleeding
• History of breast cancer
• Liver disease
• Blood clotting conditions
• Endometriosis
• Epilepsy
• Had a hysterectomy
• Heart disease or dementia
• Porphyria (a blood disorder)

Boxed Warning

There is a boxed warning from the FDA with Activella. It includes cardiovascular disorders, breast cancer, endometrial cancer, and probable dementia.

Estrogen plus progestin, such as Activella, should not be used to prevent dementia or cardiovascular disease.

There is a warning from the Women’s Health Initiative (WHI) that estrogen plus progestin carries an increased risk of pulmonary embolism (PE), deep vein thrombosis (DVT), and myocardial infarction (MI) in postmenopausal women (usually 50-79 years of age). They also have posed a warning of a higher risk of endometrial cancer in women with a uterus who are using unopposed estrogen.

Estrogen-alone therapy should also not be used for the prevention of dementia or cardiovascular disease. According to the WHI, estrogen-alone substudy carries a higher risk of DVT and stroke. There is also an increased risk of dementia in postmenopausal women who are 65 years of age or older.

• Known or suspected pregnancy; it should not be used during pregnancy
• Breast cancer or estrogen-dependent cancers due to the risk of stimulating these cancers
• Active or history of blood clots, including deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke
• Liver disease, including severe liver dysfunction or active liver disease
• Unexplained vaginal bleeding, which should be evaluated before using Activella
• Hypersensitivity to estradiol, norethindrone, or any components of Activella

Activella (estradiol/norethindrone) typically starts to relieve menopausal symptoms such as hot flashes and vaginal dryness within 1 to 4 weeks of starting treatment. However, it may take up to 3 months for full benefits to be noticeable, especially for long-term symptom relief. Always follow your doctor’s guidance for optimal results.

When Activella is taken with other prescription drugs, over-the-counter medications, vitamins, and supplements, it may change how they work or increase the frequency or severity of side effects. Make sure that you tell your healthcare professional about anything that you are taking to avoid any negative drug interactions, including:

• Inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.
• Inducers of CYP3A4 such as St. John’s wort, carbamazepine, phenobarbital, and rifampin can reduce plasma concentrations of estrogens.
• Inhibitors of CYP3A4 such as clarithromycin, erythromycin, ketoconazole, ritonavir, itraconazole, and grapefruit juice can increase plasma concentrations of estrogens, which could result in more intense side effects.

Activella comes as an estradiol/norethindrone acetate tablet, film coated in one dosage form: 1mg/0.5mg, with 1 mg of estradiol and 0.5 mg of norethindrone.

Activella should be stored away from direct sunlight, preferably in a dry place. Keep it at room temperature between 20° to 25°C (68° to 77°F) with excursions that are permitted at 15° to 30°C (59° to 86°F).

Activella is manufactured by AbbVie, a global biopharmaceutical company.

There are lower-cost generics available for Activella.

To stop taking Activella, consult your doctor. They may recommend gradually tapering the dosage instead of stopping abruptly, especially if you have been using it for a long time. This helps manage any potential withdrawal symptoms or the return of menopausal symptoms. Always follow your doctor's instructions when discontinuing any medication.

Talk to your doctor if you are already pregnant or if you have any plans to become pregnant. You should not take Activella if you are pregnant.

There have been detectable levels of progestins and estrogens found in breast milk. Because of this, you should speak to your doctor about the best way for you to feed your baby while taking Activella. In most countries, it is not recommended to breastfeed while taking this medication.