CombiPatch Side Effects

Generic name: estradiol / norethindrone

Medically reviewed by Drugs.com. Last updated on May 27, 2024.

Note: This document provides detailed information about CombiPatch Side Effects associated with estradiol / norethindrone. Some dosage forms listed on this page may not apply specifically to the brand name CombiPatch.

Applies to estradiol / norethindrone: transdermal patch extended release.

Other dosage forms:

• oral tablet

Important warnings This medicine can cause some serious health issues

Transdermal route (patch, extended release)

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.

Serious side effects of CombiPatch

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 side effects

• bloating or swelling of the face, arms, hands, lower legs, or feet
• heavy non-menstrual vaginal bleeding
• itching of the vagina or genital area
• pain during sexual intercourse
• rapid weight gain
• thick, white vaginal discharge with no odor or with a mild odor
• tingling of the hands or feet
• unusual weight gain or loss

Less common side effects

• cough or hoarseness
• fever or chills
• lower back or side pain
• painful or difficult urination

Incidence not known

• abdominal or stomach bloating or fullness
• abdominal or stomach pain
• blurred vision
• change in vaginal discharge
• clay-colored stools
• clear or bloody discharge from the nipple
• dark urine
• diarrhea
• dimpling of the breast skin
• dizziness
• gaseous abdominal or stomach pain
• headache, severe and throbbing
• hives
• hoarseness
• inverted nipple
• irritation
• itching
• joint pain, stiffness or swelling
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• lump in the breast or under the arm
• nausea and vomiting
• nervousness
• pain or feeling of pressure in the pelvis
• persistent crusting or scaling of the nipple
• pounding in the ears
• rash
• recurrent fever
• redness of the skin
• redness or swelling of the breast
• severe cramping of the uterus
• slow or fast heartbeat
• sore on the skin of the breast that does not heal
• swelling of the eyelids, face, lips, hands, or feet
• tightness in the chest
• troubled breathing or swallowing
• unpleasant breath odor
• unusual tiredness or weakness
• vaginal bleeding
• vomiting of blood
• yellow eyes or skin

Other side effects of CombiPatch

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 side effects

• acid or sour stomach
• back pain
• belching
• body aches or pain
• breast pain
• burning, itching, redness, skin rash, swelling, or soreness at the application site
• congestion
• cramps
• difficulty with moving
• discouragement
• dryness or soreness of the throat
• excess air or gas in the stomach or intestines
• feeling sad or empty
• general feeling of discomfort or illness
• headache
• heartburn
• heavy bleeding
• increased clear or white vaginal discharge
• indigestion
• irritability
• lack or loss of strength
• loss of interest or pleasure
• muscle aches and pains
• muscle stiffness
• pain during sexual intercourse
• pain or tenderness around the eyes and cheekbones
• passing gas
• shivering
• sneezing
• stomach discomfort or upset
• stuffy or runny nose
• sweating
• tender, swollen glands in the neck
• thick, white vaginal discharge with no odor or with a mild odor
• tiredness
• trouble concentrating
• trouble sleeping

Less common side effects

• blemishes on the skin
• difficulty having a bowel movement (stool)
• longer or heavier menstrual periods
• pimples

Incidence not known

• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in color of the treated skin
• decreased interest in sexual intercourse
• dizziness or lightheadedness
• dull ache or feeling of pressure or heaviness in the legs
• feeling of constant movement of self or surroundings
• inability to have or keep an erection
• increased in sexual ability, desire, drive, or performance
• increased interest in sexual intercourse
• itching skin near damaged veins
• loss in sexual ability, desire, drive, or performance
• sensation of spinning
• weight gain

For healthcare professionals

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

General adverse events

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]

Genitourinary

• 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]

Cardiovascular

• 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]

Gastrointestinal

• 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]

Psychiatric

• 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]

Other

• 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]

Musculoskeletal

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

Immunologic

• 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]

Dermatologic

• 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]

Oncologic

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

Hypersensitivity

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

Respiratory

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

Hepatic

• 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]

Metabolic

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

Ocular

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

Further information

CombiPatch side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer