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Activella

Last reviewed on RxList: 11/4/2013
Activella Side Effects Center

Last reviewed on RxList 01/06/2017

Activella (estradiol, norethindrone acetate) is a combination of the female hormones estrogen and progesterone used to treat the symptoms of menopause such as feelings of warmth in the face, neck and chest, or sudden intense spells of heat and sweating ("hot flashes" or "hot flushes"); to treat vulvar and vaginal changes (itching, burning, dryness in or around the vagina, difficulty or burning with urination) caused by menopause; and to replace estrogen in conditions such as hypogonadism, removal of the ovaries, or primary ovarian failure that result in a lack of estrogen. Activella is also used to prevent thinning of the bones (osteoporosis). Activella is available in generic form. Common side effects of Activella include:

  • stomach upset,
  • nausea,
  • vomiting,
  • bloating,
  • breast tenderness or enlargement,
  • headache,
  • weight changes,
  • weakness,
  • swelling of the hands or feet,
  • spotty darkening of the skin (particularly on the face),
  • difficulty in wearing contact lenses,
  • vaginal irritation or discomfort,
  • changes in menstrual cycle,
  • painful menstruation, or
  • break-through bleeding.

Tell your doctor if you have serious side effects of Activella including:

  • mental/mood changes (such as depression, memory loss),
  • breast lumps,
  • increased or new vaginal irritation/itching/odor/discharge,
  • severe stomach or abdominal pain,
  • persistent nausea or vomiting,
  • yellowing eyes or skin,
  • dark urine,
  • swelling hands/ankles/feet, or
  • increased thirst or urination.

Dosing of Activella is either 1.0 mg/0.5 mg (estradiol, norethindrone acetate) or 0.5 mg/0.1 mg (estradiol, norethindrone acetate). The lowest effective dose and the shortest treatment duration should be used. Activella may interact with anticoagulants (blood thinners). Other drugs may also interact with Activella. Tell your doctor all prescription or over-the-counter medicines and supplements you use. Activella must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor. This medication passes into breast milk. It may reduce the quality and amount of breast milk produced. Consult your doctor before breastfeeding.

Our Activella (estradiol, norethindrone acetate) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Activella Consumer Information

If you experience any of the following serious side effects, stop taking estradiol and norethindrone and seek emergency medical attention or notify your doctor immediately:

  • an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);
  • shortness of breath or pain in the chest;
  • a painful, red, swollen leg;
  • abnormal vaginal bleeding;
  • pain, swelling, or tenderness in the abdomen;
  • severe headache or vomiting, dizziness, faintness or changes in vision or speech;
  • yellowing of the skin or eyes; or
  • a lump in a breast.

Other, less serious side effects may be more likely to occur. Continue to take estradiol and norethindrone and talk to your doctor if you experience

  • nausea and vomiting;
  • tenderness or enlargement of the breasts;
  • weakness;
  • swelling of the hands or feet;
  • spotty darkening of the skin, particularly on the face;
  • difficulty in wearing contact lenses;
  • vaginal irritation or discomfort; or
  • changes in menstrual cycle, painful menstruation, or break-through bleeding.

Estradiol increases the risk of developing endometrial hyperplasia, a condition that may lead to cancer of the lining of the uterus. Using a progestin, such as norethindrone, with estradiol lowers the risk of developing this condition. Visit your doctor regularly and report any unusual vaginal bleeding right away.

It is unclear to what extent estrogen and progesterone treatments may affect the risk of breast cancer.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Activella (Estradiol, Norethindrone Acetate)

Activella Professional Information

SIDE EFFECTS

The following serious adverse reactions are discussed elsewhere in the labeling:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions reported with Activella 1 mg/0.5 mg by investigators in the Phase 3 studies regardless of causality assessment are shown in Table 1.

TABLE 1 : ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ACTIVELLA 1 MG/0.5 MG

  Endometrial Hyperplasia Study (12-Months) Vasomotor Symptoms Study (3-Months) Osteoporosis Study (2-Years)
Activella1 mg/0.5 mg
(n=295)
1 mg E2
(n=296)
Activella1 mg/0.5 mg
(n=29)
Placebo
(n=34)
Activella1 mg/0.5 mg
(n=47)
Placebo (n=48)
Body as a Whole
  Back Pain 6% 5% 3% 3% 6% 4%
  Headache 16% 16% 17% 18% 11% 6%
Digestive System
  Nausea 3% 5% 10% 0% 11% 0%
  Gastroenteritis 2% 2% 0% 0% 6% 4%
Nervous System
  Insomnia 6% 4% 3% 3% 0% 8%
  Emotional Lability 1% 1% 0% 0% 6% 0%
Respiratory System
  Upper Respiratory 18% 15% 10% 6% 15% 19%
Tract Infection
  Sinusitis 7% 11% 7% 0% 15% 10%
Metabolic and Nutritional
  Weight Increase 0% 0% 0% 0% 9% 6%
Urogenital System
  Breast Pain 24% 10% 21% 0% 17% 8%
  Post-Menopausal Bleeding 5% 15% 10% 3% 11% 0%
  Uterine Fibroid 5% 4% 0% 0% 4% 8%
  Ovarian Cyst 3% 2% 7% 0% 0% 8%
Resistance Mechanism
  Infection Viral 4% 6% 0% 3% 6% 6%
  Moniliasis Genital 4% 7% 0% 0% 6% 0%
Secondary Terms
  Injury Accidental 4% 3% 3% 0% 17%* 4%*
  Other Events 2% 3% 3% 0% 6% 4%
* including one upper extremity fracture in each group

Adverse reactions reported with Activella 0.5 mg/0.1 mg by investigators during the Phase 3 study regardless of causality assessment are shown in Table 2.

TABLE 2 : ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ACTIVELLA 0.5 MG/0.1 MG

  Activella 0.5 mg/0.1 mg
(n=194)
Placebo
(n=200)
Body as a Whole
  Back Pain 10% 4%
  Headache 22% 19%
  Pain in extremity 5% 4%
Digestive System
  Nausea 5% 4%
  Diarrhea 6% 6%
Respiratory System
  Nasopharyngitis 21% 18%
  Urogenital System Endometrial thickening 10% 4%
  Vaginal hemorrhage 26% 12%

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Activella. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Genitourinary System

Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; pre-menstrual-like syndrome; cystitis-like syndrome; ovarian cancer; endometrial hyperplasia; endometrial cancer.

Breast

Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.

Cardiovascular

Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction, stroke; increase in blood pressure.

Gastrointestinal

Nausea, vomiting; changes in appetite; cholestatic jaundice; abdominal pain/cramps, flatulence, bloating; increased incidence of gallbladder disease and pancreatitis.

Skin

Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; seborrhea; hirsutism; itching; skin rash; pruritus.

Eyes

Retinal vascular thrombosis, intolerance to contact lenses.

Central Nervous System

Headache; migraine; dizziness; mental depression; chorea; insomnia; nervousness; mood disturbances; irritability; exacerbation of epilepsy; dementia.

Miscellaneous

Increase or decrease in weight; edema; leg cramps; changes in libido; fatigue; exacerbation of asthma; increased triglycerides; hypersensitivity; anaphylactoid/anaphylactic reactions.

Read the entire FDA prescribing information for Activella (Estradiol, Norethindrone Acetate)

Related Resources for Activella

Read the Activella User Reviews »

© Activella Patient Information is supplied by Cerner Multum, Inc. and Activella Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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