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Generic Name: estradiol and norethindrone (transdermal) (ES tra DYE ol and nor ETH in drone)
Brand Name: Combipatch
Physician reviewed Combipatch (transdermal) (transdermal) patient information - includes Combipatch (transdermal) description, dosage and directions.
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Drug Information:
Estradiol is a form of estrogen, a female sex hormone that regulates many processes in the body. Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation. Combipatch (skin patch) is a combination medicine used to treat menopause symptoms such as hot flashes and vaginal changes (itching, burning, dryness). Combipatch is also used before menopause to treat a lack of estrogen caused by conditions such as hypogonadism, primary ovarian failure, or surgical removal of the ovaries. Learn more

Combipatch Side Effects

CombiPatch Side Effects

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 CombiPatch.

In Summary

Common side effects of CombiPatch include: asthenia, dysmenorrhea, menstrual disease, pharyngitis, vaginitis, back pain, and mastalgia. Other side effects include: nervousness. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to estradiol/norethindrone: oral tablet

Other dosage forms:

  • transdermal patch extended release


Oral route (Tablet)

Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. An increased risk of DVT, pulmonary embolism, stroke, myocardial infarction, and invasive breast cancer have been reported. An increased risk of probable dementia in postmenopausal women 65 years of age or older has also been reported. There is an increased risk of endometrial cancer in women with a uterus who use unopposed estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

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.


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

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


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


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


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


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


Very common (10% or more): Back pain (10%)

Common (1% to 10%): Pain in extremity, leg cramps


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


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


Uncommon (0.1% to 1%): Breast cancer

Rare (less than 0.1%): Uterine leiomyoma

Postmarketing reports: Ovarian cancer, endometrial cancer


Uncommon (0.1% to 1%): Hypersensitivity

Rare (less than 0.1%): Allergic reaction

Postmarketing reports: Anaphylactoid/anaphylactic reactions


Rare (less than 0.1%): Pulmonary embolism, asthma

Postmarketing reports: Exacerbation of asthma


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


Common (1% to 10%): Fluid retention

Postmarketing reports: Changes in appetite, increased triglycerides


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

Editorial References and Review

Medically reviewed by BestRx Medical Team Last updated on 1/1/2020.

Source: Drugs.com Combipatch