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Activella Side Effects

Generic Name: estradiol / norethindrone

Note: This document contains side effect information about estradiol / norethindrone. Some of the dosage forms listed on this page may not apply to the brand name Activella.

For the Consumer

Applies to estradiol/norethindrone: oral tablet

Along with its needed effects, estradiol / norethindrone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking estradiol / norethindrone:

More common
  • Body aches or pain
  • chills or fever
  • cold or flu-like symptoms
  • difficulty breathing
  • headache
  • itching of the vagina or genital area
  • nonmenstrual vaginal bleeding
  • pain during sexual intercourse
  • thick, white vaginal discharge with no odor or with a mild odor
  • unusual tiredness or weakness
Incidence not known
  • Abdominal or stomach pain
  • blistering, peeling, or loosening of the skin
  • change in vaginal discharge
  • chest pain, discomfort, or tightness in chest
  • clay-colored stools
  • clear or bloody discharge from the nipple
  • confusion
  • dark urine
  • difficulty speaking
  • difficulty swallowing
  • dizziness or lightheadedness
  • double vision
  • fainting
  • fast heartbeat
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • joint or muscle pain
  • loss of appetite
  • lump in the breast or under the arm
  • nausea and vomiting
  • noisy breathing
  • pain in the ankles or knees
  • pain or discomfort in the arms, jaw, back, or neck
  • pain or feeling of pressure in the pelvis
  • pain, redness, or swelling in the arm or leg
  • painful, red lumps under the skin, mostly on the legs
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • problems with memory or speech
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • red, irritated eyes
  • redness or swelling of the breast
  • skin rash, hives, or itching
  • sores, ulcers, or white spots in the mouth or on the lips
  • sudden shortness of breath or troubled breathing
  • sweating
  • trouble recognizing objects
  • trouble thinking and planning
  • trouble walking

Some side effects of estradiol / norethindrone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Back pain
  • breast pain
  • cramps
  • crying
  • euphoria
  • mental depression
  • paranoia
  • quick to react or overreact emotionally
  • rapidly changing moods
  • trouble sleeping
  • weakness
  • weight gain
Incidence not known
  • Changes in appetite
  • changes in sexual ability, desire, drive, or performance
  • excess air or gas in the stomach or intestines
  • increased hair growth, especially on the face
  • patchy brown or dark brown discoloration of the skin
  • trouble wearing contact lenses

For Healthcare Professionals

Applies to estradiol / norethindrone: oral tablet, transdermal film extended release


The most common adverse events were vaginal bleeding and breast pain/tenderness. Vaginal bleeding usually occurred in the first months of treatment. Breast pain usually disappeared after a few months of therapy.[Ref]


Very common (10% or more): Vaginal hemorrhage (26%), breast pain (24%), post-menopausal bleeding (11%), endometrial thickening (10%), breast tenderness, menstruation irregular
Common (1% to 10%): Ovarian cyst, uterine fibroid, breast edema, breast enlargement, uterine fibroids aggravated, uterine fibroids recurrence, uterine fibroids
Uncommon (0.1% to 1%): Endometrial hyperplasia, dysmenorrhea
Rare (less than 0.1%): Fallopian tube cysts, endocervical polyps
Postmarketing reports: Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow, breakthrough bleeding, spotting, increase in size of uterine leiomyomata, change in amount of cervical secretion, changes in cervical ectropion, pre-menstrual-like syndrome, cystitis-like syndrome, nipple discharge, galactorrhea, fibrocystic breast changes, vulvovaginal pruritus[Ref]

Nervous system

Very common (10% or more): Headache (22%)
Common (1% to 10%): Migraine or migraine aggravated, dizziness
Rare (less than 0.1%): Paresthesia
Postmarketing reports: Dizziness, exacerbation of epilepsy, dementia, chorea, stroke[Ref]


Common (1% to 10%): Blood pressure increase
Uncommon (0.1% to 1%): Thrombophlebitis superficial, venous thromboembolism
Rare (less than 0.1%): Thrombophlebitis deep, deep venous thromboembolism
Postmarketing reports: Deep and superficial vein thrombosis, thrombophlebitis, myocardial infarction, stroke, hypertension aggravated[Ref]


Very common (10% or more): Nausea (11%)
Common (1% to 10%): Gastroenteritis, diarrhea, abdominal pain, abdominal distention, abdominal discomfort
Uncommon (0.1% to 1%): Flatulence, bloating
Postmarketing reports: Vomiting, abdominal cramps, pancreatitis, dyspepsia[Ref]


Common (1% to 10%): Insomnia, emotional lability, depression or depression aggravated
Uncommon (0.1% to 1%): Nervousness, changes in libido
Postmarketing reports: Mental depression, mood disturbances, irritability, anxiety[Ref]


Very common (10% or more): Accidental injury (17%)
Common (1% to 10%): Weight increase, weight decreased, edema peripheral, pain, asthenia
Uncommon (0.1% to 1%): Drug ineffective
Postmarketing reports: Fatigue, edema[Ref]


Very common (10% or more): Back pain (10%)
Common (1% to 10%): Pain in extremity, leg cramps[Ref]


Very common (10% or more): Nasopharyngitis (21%), upper respiratory tract infection (18%), sinusitis (15%)
Common (1% to 10%): Infection viral, moniliasis genital, genital candidiasis or vaginitis[Ref]


Common (1% to 10%): Acne, rash, pruritus, dry skin
Uncommon (0.1% to 1%): Alopecia, hirsutism, urticaria, skin reactions, skin discoloration
Postmarketing reports: Chloasma or melasma that may persist when drug is discontinued, erythema multiforme, erythema nodosum, hemorrhagic eruption, loss of scalp hair, seborrhea, skin rash, seborrhea, angioneurotic edema[Ref]


Uncommon (0.1% to 1%): Breast cancer
Rare (less than 0.1%): Uterine leiomyoma
Postmarketing reports: Ovarian cancer, endometrial cancer[Ref]


Uncommon (0.1% to 1%): Hypersensitivity
Rare (less than 0.1%): Allergic reaction
Postmarketing reports: Anaphylactoid/anaphylactic reactions[Ref]


Rare (less than 0.1%): Pulmonary embolism, asthma
Postmarketing reports: Exacerbation of asthma[Ref]


Uncommon (0.1% to 1%): Gallbladder disease, gallstones, transaminases increased
Rare (less than 0.1%): Cholelithiasis
Postmarketing reports: Cholestatic jaundice, gallbladder disease, cholelithiasis aggravated, cholelithiasis recurrence[Ref]


Common (1% to 10%): Fluid retention
Postmarketing reports: Changes in appetite, increased triglycerides[Ref]


Postmarketing reports: Retinal vascular thrombosis, intolerance to contact lenses, visual disturbances[Ref]


1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

2. Cerner Multum, Inc. "Australian Product Information." O 0

3. "Product Information. Amabelz (estradiol-norethindrone)." Lupin Pharmaceuticals Inc, Baltimore, MD.

4. "Product Information. Lopreeza (estradiol-norethindrone)." Amneal Pharmaceuticals, Glasgow, KY.

5. "Product Information. Mimvey (estradiol-norethindrone)." Teva Pharmaceuticals USA, North Wales, PA.

6. "Product Information. Activella (estradiol-norethindrone)." Gemini Laboratories, Bridgewater, NJ.

Some side effects of Activella may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.