Combipatch
CombiPatch (estradiol / norethindrone) is a type of hormone replacement therapy. It treats symptoms of menopause, such as hot flashes, night sweats, and vaginal dryness. This combination medication also restores estrogen levels in people with medical conditions that cause low estrogen. It's a patch that's applied onto the skin twice a week. Common side effects include headache and breast pain.
What is CombiPatch (estradiol / norethindrone)?
What is CombiPatch (estradiol / norethindrone) used for?
In people who have a healthy uterus:
Moderate-to-severe symptoms of menopause, like hot flashes, night sweats, vaginal dryness, and vaginal irritation
Low estrogen levels caused by certain health conditions (e.g., ovaries aren't working as they should)
How CombiPatch (estradiol / norethindrone) works
CombiPatch (estradiol / norethindrone) is a combination of two hormones. They work to balance hormonal changes that your body goes through during menopause and with certain medical conditions that cause low estrogen.
Estradiol is a type of estrogen. It restores the estrogen levels in your body. This relieves symptoms of low estrogen, such as hot flashes, night sweats, vaginal dryness, and vaginal irritation.
Norethindrone is a type of progestin. It acts like progesterone and helps balance the effect of estrogen on the growth of your uterine lining.
Drug Facts
Get your GoodRx coupon
What are the side effects of CombiPatch (estradiol / norethindrone)?
Common Side Effects
- Breast pain (25-31%)
- Menstrual cramps (20-21%)
- Headache (18-20%)
- Vaginitis (e.g., vaginal pain, itching, burning, or discharge; 6-13%)
- Weakness (8-12%)
- Breathing problems (7-12%)
- Irregular vaginal bleeding or other related menstrual issues (6-12%)
- Back pain (9-11%)
- Nausea (8-11%)
- Sore throat (4-10%)
Other Side Effects
- Application site reactions (e.g., irritation, itchiness, redness, swelling, rash, dry skin)
- Vaginal discharge
- General pain
- Stomach pain
- Diarrhea
- Indigestion or heartburn
- Passing gas
- Flu-like symptoms
- Runny nose
- Sinus infection
- Depression
- Trouble sleeping
- Nervousness
Serious Side Effects
- Blood clot in arm or leg: swelling, pain, or tenderness in the arm or leg; skin that's warm to the touch
- Blood clot in the lung: trouble breathing, chest pain
- Heart attack: chest pain, arm pain, shortness of breath, cold sweat, lightheadedness
- Stroke: sudden weakness on one side of the body, drooping face, changes in your speech or vision, confusion, bad headache
- Severe allergic reaction: hives; itchiness; stomach pain; vomiting; trouble breathing; swelling of the face, lips, or tongue
Source:Â DailyMed
The following side effects have also been reported
Along with its needed effects, a medicine 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:
More common
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
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
dimpling of the breast skin
dizziness
gaseous abdominal or stomach pain
headache, severe and throbbing
hoarseness
inverted nipple
irritation
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
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
Some side effects 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
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
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
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
Blemishes on the skin
difficulty having a bowel movement (stool)
longer or heavier menstrual periods
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
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Pros and cons of CombiPatch (estradiol / norethindrone)
Pros
Can help relieve both hot flashes and vaginal dryness
Approved for both people who have and haven't gone through menopause (under certain situations)
Available as a patch that's applied onto the skin; an alternative to pills or vaginal creams
Cons
Must change the patch twice a week
Can fall off if the patch gets wet and rubs against something
Chance for irregular vaginal bleeding or withdrawal bleeding
No lower-cost generic available; brand name only
Pharmacist tips for CombiPatch (estradiol / norethindrone)
You should use the lowest dose of CombiPatch (estradiol / norethindrone) for the shortest period of time possible to lower the risk for serious side effects. Follow up with your prescriber every few months about your symptoms and about how the medication is working for you.
Apply CombiPatch (estradiol / norethindrone) onto the skin of your lower stomach twice a week (every 3 to 4 days). Mark when you need to change your patch on your calendar to help you remember.
Remove the worn CombiPatch (estradiol / norethindrone) before you apply a new one on. Don't put more than one patch onto the skin at any time to lower your risk for side effects, such as breast pain, menstrual cramps, and headache.
You might have spotting and irregular vaginal bleeding if you stop using CombiPatch (estradiol / norethindrone) or if you forget to apply a new patch on every 3 to 4 days. Symptoms of low estrogen levels or menopause might also come back.
You can get CombiPatch (estradiol / norethindrone) wet, but the patch might fall off if it gets rubbed on. Make sure to check whether your patch is still on your skin or whether it has fallen off after you use a sauna, bathe, shower, or swim.
Where to apply CombiPatch (estradiol / norethindrone):
Apply CombiPatch (estradiol / norethindrone) onto an area of smooth, clean, dry skin on your lower stomach. Avoid areas near your waistline, since the patch can fall off if your clothes or belt rubs against it.
Place each new patch onto a different area of skin to avoid skin irritation. Avoid applying patches onto the same area of skin in the same week.
Don't apply the patch on or near your breasts. The active hormones in the patch can get absorbed into your breasts, which can raise your risk for side effects.
Don't apply the patch onto any injured, burned, scarred, or tattooed skin. Also avoid areas of hairy skin so that it doesn't hurt when you peel the patch off later.
When you're ready to apply a new patch onto your skin, open the pouch at the indented notch with your hand. Don't use scissors to open the pouch to avoid cutting the patch by mistake.
Peel off the plastic film that's attached to the thicker protective backing. Try not to touch the sticky side of the patch with your fingers to prevent accidental exposure to active hormones.
Place the sticky side of the patch onto the skin on the lower part of your stomach. Press the entire patch against your skin with your hand for about 10 seconds and smooth down the edges. These steps help the patch stick onto your skin well.
How to remove and throw away used CombiPatch (estradiol / norethindrone):
Slowly peel the patch from your skin. Avoid touching the sticky side of the patch with your fingers because the used patch might still have active hormones on it.
Fold the sticky sides of the patch together, place it in a strong child-proof container, and then throw the container away in the trash. Don't flush the patch down the toilet.
To get rid of any stickiness left on your skin, let the area dry for 15 minutes and then rub with oil or lotion to remove the adhesive.
Frequently asked questions about CombiPatch (estradiol / norethindrone)
How to save using GoodRx
What are the risks and warnings for CombiPatch (estradiol / norethindrone)?
CombiPatch (estradiol / norethindrone) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Risk for blood clots and other complications
Risk factors: Personal or family history of blood clots | High blood pressure | Diabetes | High cholesterol | Tobacco use | People who identify as obese | Systemic lupus erythematosus (SLE)
Estrogen/progestin combination therapies such as CombiPatch (estradiol / norethindrone) can raise your risk for blood clots. Sometimes, these blood clots can lead to a heart attack or stroke. Because of these risks, estrogen/progestin therapies shouldn't be used to prevent heart disease.
Tell your prescriber about your full medical history so they can check your risk for blood clots. Also tell your prescriber about any planned procedures that you might need a long period of bedrest afterwards. Your prescriber will let you know when to stop the medication before your procedure and restart it afterwards to lessen your risk for blood clots. In general, you should take the lowest dose of CombiPatch (estradiol / norethindrone) for the shortest period of time possible to lower your risk for blood clots.
Be aware of the signs and symptoms of a blood clot, heart attack, and stroke.
Blood clot in arm or leg: swelling or pain in the arm or leg
Blood clot in the lung: chest pain, trouble breathing
Blood clot in the eye: sudden partial or complete vision loss, bulging eyes, double vision
Heart attack (blood clot near the heart): chest pain, arm pain, shortness of breath, a cold sweat, lightheadedness
Stroke (blood clot in the brain): sudden weakness on one side of the body, drooping face, trouble breathing, bad headache, changes in speech or vision
Take off CombiPatch (estradiol / norethindrone) and get medical help right away if you have any signs or symptoms of a blood clot.
Risk for breast cancer
Risk factors: Personal or family history of breast cancer | Previous hormonal therapy | Taking hormonal therapy for a long period of time
Studies suggest that estrogen/progestin combination therapies like CombiPatch (estradiol / norethindrone) might raise the risk for breast cancer. This risk might be higher than that with estrogen-only therapy. The risk might also be greater if you've taken hormonal therapy before or if you've taken hormonal therapy for several years. Don't take CombiPatch (estradiol / norethindrone) if you currently have or have had breast cancer in the past.
To lower your risk for breast cancer, you should take the lowest dose of CombiPatch (estradiol / norethindrone) for the shortest period of time possible. Regularly check your breasts for any changes and get recommended breast scans (mammograms) done. Let your prescriber know if you notice any unusual changes in breast shape, size, or color.
Risk for uterine cancer (also called endometrial cancer)
Risk factors: Estrogen therapy without additional progestin | People with a healthy uterus | Using estrogen therapy for more than 1 year | High estrogen dose
CombiPatch contains estradiol (an estrogen) and norethindrone (a progestin). Estrogens can thicken and change the lining of your uterus called the endometrium. This can lead to uncontrolled growth of the uterine lining and put people with a healthy uterus at risk for uterine cancer (or endometrial cancer). The progestin that's in CombiPatch helps balance out estrogen's effect on the growth of the uterine lining, which helps protect the uterus.
Even though CombiPatch (estradiol / norethindrone) has a progestin to protect the uterus against the potential effects of estrogen, it's important to be aware of the warning signs of endometrial cancer, including vaginal bleeding that doesn't go away or keeps coming back and pelvic pain. Talk with your prescriber if you're worried about the risk for endometrial cancer. Let your prescriber know if you notice any unusual vaginal bleeding or pelvic pain.
Risk for ovarian cancer
Risk factors: Taking hormonal therapy for menopausal symptoms
Some studies suggest that people who take hormonal therapy like CombiPatch (estradiol / norethindrone) for menopausal symptoms might be at a slightly higher risk for ovarian cancer. Speak with your prescriber if you're concerned about the risk for ovarian cancer. Let your care team know if you notice any unusual bloating, pelvic pain, trouble eating, or feeling full quickly. These can be signs of ovarian cancer.
Risk for dementia
Risk factors: Age 65 years or older
People age 65 years and older who take estrogen/progestin combination therapies like CombiPatch (estradiol / norethindrone) might be at greater risk for dementia. Estrogen/progestin combination therapies shouldn't be used to prevent dementia.
Be aware of the early signs and symptoms of dementia, such as becoming confused or more forgetful, getting lost, and having trouble doing familiar things at home or at work. Speak with your prescriber if the risk of dementia worries you.
Gallbladder or liver problems in certain people
Risk factors: History of liver disease or jaundice
The risk for gallbladder problems is higher for people who've gone through menopause and are taking estrogen therapy like CombiPatch (estradiol / norethindrone). Let your prescriber know if you've previously had jaundice (yellowing of your skin or whites of the eyes). Tell your care team if you start having jaundice, stomach pain that doesn't go away, nausea, or vomiting while you're taking this medication. These can be signs of liver damage or gallbladder problems.
Buildup of fluids in your body (fluid retention)
Risk factors: Certain heart conditions | Kidney damage
Estrogen/progestin combination therapies like CombiPatch (estradiol / norethindrone) can make your body hold onto extra fluids. This can cause swelling of your hands, ankles, and feet. Fluid retention can worsen certain heart conditions, like heart failure, and kidney damage. Tell your healthcare team if you notice any signs of worsening fluid retention while you're taking CombiPatch (estradiol / norethindrone) if you have heart or kidney problems.
High triglyceride (fat) levels
Risk factors: History of high triglyceride levels in the blood
Let your prescriber know if you have a history of having high triglyceride levels. It's possible that estrogens like estradiol can raise the triglyceride (fat) levels in your blood. And having too much triglycerides in the blood can lead to swelling of the pancreas (pancreatitis). Tell your care team right away if you have symptoms of pancreatitis, like stomach pain that spreads to your back, stomach tenderness, fever, nausea, or vomiting.
Low thyroid hormone levels
Risk factors: Conditions that cause low thyroid hormone levels
Estrogen-containing therapies, like CombiPatch (estradiol / norethindrone), can cause changes to the thyroid hormone levels in the body. It's harder for people with low thyroid hormone levels (hypothyroidism) to adjust to these changes than for an average person. If you have hypothyroidism, work with your prescriber to adjust the dose of your thyroid medication while you're taking CombiPatch (estradiol / norethindrone).
Changes in calcium levels in certain people
Risk factors: Breast cancer | Cancer that has spread to the bones | Low parathyroid hormone levels
Estrogen therapy, such as CombiPatch (estradiol / norethindrone), can change the calcium levels in your blood. People with breast cancer and cancer that's spread to the bones are at higher risk of dangerously high calcium levels while they're taking estrogens. Let your care team know if you have any symptoms of high calcium levels, like tiredness, muscle weakness, bone pain, nausea, and constipation.
On the other hand, estrogen therapy can make calcium levels drop in people with low parathyroid hormone levels. Contact your care team if you have symptoms of low calcium levels, such as muscle cramps; brittle nails; and tingling in your lips, fingers, or feet.
CombiPatch (estradiol / norethindrone) dosage forms
Typical dosing for CombiPatch (estradiol / norethindrone)
Typically, you'll start with a patch that releases 0.05 mg of estradiol and 0.14 mg of norethindrone per day. You can switch to a patch with a higher dose of norethindrone, if needed (this patch releases 0.05 mg of estradiol and 0.25 mg of norethindrone per day).
The dose depends on whether you're taking CombiPatch (estradiol / norethindrone) by itself or with an estradiol-only patch like Climara.
Taking CombiPatch (estradiol / norethindrone) by itself
Apply 1 patch onto your lower stomach below your waistline, and replace it twice a week (every 3 to 4 days).
Taking CombiPatch (estradiol / norethindrone) together with an estradiol-only patch
Days 1 to 14: Apply 1 estradiol-only patch (0.05 mg of estradiol per day) onto your skin, and replace it twice a week (every 3 to 4 days).
Days 15 to 28: Apply 1 CombiPatch (estradiol / norethindrone) onto your lower stomach, and replace it twice a week (every 3 to 4 days).
Interactions between CombiPatch (estradiol / norethindrone) and other drugs
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Abametapir
- Amifampridine
- Amoxicillin
- Ampicillin
- Amprenavir
- Apalutamide
- Aprepitant
- Armodafinil
- Artemether
- Bacampicillin
- Betamethasone
- Bexarotene
- Bosentan
- Brigatinib
- Bupropion
- Carbamazepine
- Carbenicillin
- Cefaclor
- Cefadroxil
- Cefdinir
- Cefditoren
- Cefixime
- Cefpodoxime
- Cefprozil
- Ceftazidime
- Ceftibuten
- Cefuroxime
- Cenobamate
- Ceritinib
- Clavulanic Acid
- Clobazam
- Cloxacillin
- Colesevelam
- Conivaptan
- Cyclacillin
- Cyclosporine
- Dabrafenib
- Darunavir
- Dexamethasone
- Dicloxacillin
- Donepezil
- Doxycycline
- Efavirenz
- Elagolix
- Elvitegravir
- Encorafenib
- Enzalutamide
- Eslicarbazepine Acetate
- Etravirine
- Fosamprenavir
- Fosaprepitant
- Fosnetupitant
- Fosphenytoin
- Griseofulvin
- Guar Gum
- Isotretinoin
- Ivosidenib
- Lesinurad
- Lixisenatide
- Lorlatinib
- Lumacaftor
- Minocycline
- Mitotane
- Modafinil
- Mycophenolate Mofetil
- Mycophenolic Acid
- Nafcillin
- Nelfinavir
- Netupitant
- Nevirapine
- Octreotide
- Oxacillin
- Oxcarbazepine
- Oxytetracycline
- Penicillin G
- Penicillin G Procaine
- Penicillin V
- Phenobarbital
- Phenylbutazone
- Phenytoin
- Pitolisant
- Pixantrone
- Prednisone
- Primidone
- Red Clover
- Rifabutin
- Rifampin
- Rifapentine
- Ritonavir
- Rufinamide
- Secobarbital
- St John's Wort
- Sugammadex
- Sultamicillin
- Tazemetostat
- Telaprevir
- Tetracycline
- Theophylline
- Ticarcillin
- Tigecycline
- Tizanidine
- Topiramate
- Troglitazone
- Ulipristal
- Valproic Acid
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Amitriptyline
- Atazanavir
- Clomipramine
- Diazepam
- Doxepin
- Ginseng
- Imipramine
- Lamotrigine
- Levothyroxine
- Licorice
- Lorazepam
- Parecoxib
- Prednisolone
- Selegiline
- Tacrine
- Temazepam
- Tipranavir
- Triazolam
- Troleandomycin
- Valdecoxib
- Voriconazole
- Warfarin
How much does CombiPatch (estradiol / norethindrone) cost?
CombiPatch (estradiol / norethindrone) contraindications
Abnormal vaginal bleeding that a healthcare professional hasn't diagnosed yet
Currently have or have had breast cancer
Currently have or have had an estrogen-dependent cancer or tumor
Currently have or have had a blood clot (e.g., DVT, PE)
History of heart attack or stroke
Liver damage or liver problems
Blood-clotting conditions
Currently pregnant
What are alternatives to CombiPatch (estradiol / norethindrone)?
In people who have a healthy uterus:
Moderate-to-severe symptoms of menopause, like hot flashes, night sweats, vaginal dryness, and vaginal irritation
Low estrogen levels caused by certain health conditions (e.g., ovaries aren't working as they should)
Treatment of moderate-to-severe symptoms of menopause (e.g., hot flashes, night sweats) for people with a healthy uterus
Prevention of osteoporosis for people who've gone through menopause with a healthy uterus
Moderate-to-severe vasomotor symptoms (VMS) of menopause, like hot flashes and night sweats
Moderate-to-severe symptoms of vulvar and vaginal atrophy, like vaginal dryness
Prevention of osteoporosis in females who've reached menopause
What is the latest news about CombiPatch (estradiol / norethindrone)?
CombiPatch (estradiol / norethindrone) images
Get savings updates for CombiPatch (estradiol / norethindrone)
Receive price alerts, news, and other messages from GoodRx about CombiPatch (estradiol / norethindrone) and other healthcare topics and relevant savings offers.By signing up, I agree to GoodRx's Terms and Privacy Policy, and to receive marketing messages from GoodRx.
References
Best studies we foundAdler, G., et al. (2005). A multicenter, open-label study to evaluate satisfaction and menopausal quality of life in women using transdermal estradiol/norethindrone acetate therapy for the management of menopausal signs and symptoms. Gynecologic and Obstetric Investigation.
American Cancer Society. (2018). Signs and symptoms of ovarian cancer.
American Cancer Society. (2018). What is ovarian cancer?
American Cancer Society. (2019). Endometrial cancer risk factors.
American Cancer Society. (2019). Signs and symptoms of endometrial cancer.
American Cancer Society. (2019). What is endometrial cancer?
American Cancer Society. (2021). Ovarian cancer risk factors.
Kim, J. J., et al. (2010). Role of progesterone in endometrial cancer. Seminars in Reproductive Medicine.
Lewis, J. L., III. (2023). Hypocalcemia (low level of calcium in the blood). Merck Manual Consumer Version.
Marsh, M. S., et al. (1994). Paradoxical effects of hormone replacement therapy on breast tenderness in postmenopausal women. Maturitas.
Mastorakos, G., et al. (2021). Progestins and the risk of breast cancer. Acta Endocrinologica.Â
MedlinePlus. (2023). Calcium blood test.
MedlinePlus. (2024). Primary ovarian insufficiency.
Nappi, R. E., et al. (2001). Course of primary headaches during hormone replacement therapy. Maturitas.
Noven Therapeutics, LLC. (2024). Combipatch (estradiol/norethindrone acetate transdermal system)- estradiol/norethindrone acetate transdermal system patch, extended release [package insert]. DailyMed.
Ospina, N. S., et al. (2022). Hypoparathyroidism. Endocrine Society.
Stuenkel, C., et al. (2022). Menopause. Endocrine Society.
Yu, K., et al. (2022). Estrogen receptor function: Impact on the human endometrium. Frontiers in Endocrinology.
Compare other Menopause, Estrogen Replacement drugs
Browse medications
View AllResearch prescriptions and over-the-counter medications from A to Z, compare drug prices, and start saving.