estradiol/norethindrone
Brand names: Activella, CombiPatch
CombiPatch is a skin patch that contains estrogen and progestin hormones. It is used to treat menopause symptoms and conditions caused by low estrogen.
Drug Pricing (NADAC)
Brand Price
$29.78/unit
Generic Available
No
NOVEN PHARMS INC
Pricing data from NADAC (CMS), effective November 20, 2024. Compare all drug costs →
What it does
CombiPatch treats moderate to severe hot flashes caused by menopause.
Common side effects
Abdominal pain, Back pain, Headache
Key warnings
This medicine has serious warnings.
How It Works
CombiPatch delivers estrogen and progestin through your skin into your bloodstream. These hormones help to replace the ones your body is no longer making. This can reduce menopause symptoms and treat conditions caused by low estrogen.
How to Take It
Apply the CombiPatch to your lower abdomen twice a week, every 3 to 4 days. Apply a new patch each time. Your doctor may have you use it continuously or in a cycle with an estrogen-only patch. Follow your doctor's instructions carefully.
Pregnancy & Breastfeeding
You should not use CombiPatch if you are pregnant or think you might be pregnant. Talk to your doctor if you are breastfeeding before using this medicine, as it may pass into breast milk.
Missed Dose
Apply a new patch as soon as you remember. Then, change your patch on your regular schedule.
Storage
Store CombiPatch in the refrigerator between 36°F to 46°F (2°C to 8°C) in the sealed foil pouch.
Side Effects (from patient reports)
Based on 45,381 FDA adverse event reports.
Serious Warnings
This medicine has serious warnings. It can increase your risk of blood clots, stroke, heart attack, dementia, and breast cancer. If you have a uterus, taking estrogen alone can increase your risk of uterine cancer. Talk to your doctor about the risks and benefits of CombiPatch.
Known Drug Interactions
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, nelfinavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.
Mechanism: Ketoconazole slows down the liver's ability to break down estrogen. This can cause the amount of estrogen in your blood to rise, which may lead to more side effects.
What to do: Your doctor should monitor you for side effects and may need to adjust your hormone dose.
John’s wort ( Hypericum perforatum ) preparations, anticonvulsants (e.g., phenobarbital, phenytoin and carbamazepine), phenylbutazone, and anti-infectives (e.g., rifampin, rifabutin, nevirapine and efavirenz) may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.
Mechanism: Carbamazepine makes your body process and remove estrogen faster than normal. This can make the hormone therapy less effective and might cause unexpected bleeding.
What to do: Your doctor may need to adjust your dose or check if the medication is still working correctly.
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, nelfinavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.
Mechanism: Erythromycin blocks the enzyme that usually clears estrogen from your system. This leads to higher levels of estrogen in your body, which can increase the risk of side effects.
What to do: Tell your doctor if you experience new side effects, as they may need to change your dosage.
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, nelfinavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.
Mechanism: Clarithromycin interferes with how your body breaks down estrogen. This causes the hormone to build up in your blood, potentially causing more side effects.
What to do: Your healthcare provider may need to monitor you closely or adjust your medication levels while you are taking both drugs.
John’s wort ( Hypericum perforatum ) preparations, anticonvulsants (e.g., phenobarbital, phenytoin and carbamazepine), phenylbutazone, and anti-infectives (e.g., rifampin, rifabutin, nevirapine and efavirenz) may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.
Mechanism: Rifampin speeds up the breakdown of estrogen in your body. This can lower the amount of medicine in your blood, making it less effective and causing changes in your period.
What to do: You should talk to your doctor about this combination, as they may need to adjust your treatment to ensure it still works.
Common Questions
Can CombiPatch prevent heart disease?
Can CombiPatch prevent dementia?
What should I do if the patch falls off?
Can I use CombiPatch if I have a history of blood clots?
Can I use CombiPatch if I have liver problems?
How often should I change the CombiPatch?
Where should I apply the CombiPatch?
What if I experience irregular bleeding?
Can I use CombiPatch if I have breast cancer?
What should I do if I have abnormal vaginal bleeding?
What are the common side effects of estradiol/norethindrone?
Does estradiol/norethindrone interact with other medications?
What drug class is estradiol/norethindrone?
Is estradiol/norethindrone safe during pregnancy?
Related Medications in Estrogen / Progestin Combination
Other drugs grouped near estradiol/norethindrone — same-class peers and common alternatives.
abiraterone
Zytiga
Abiraterone (Zytiga) is a medicine used with prednisone to treat prostate cancer that has spread.
Compare with estradiol/norethindrone →
anastrozole
Arimidex
Anastrozole is a medicine used to treat breast cancer in women after menopause.
Compare with estradiol/norethindrone →
bazedoxifene/conjugated estrogens
Duavee
Duavee is a combination medicine containing estrogen and a drug that blocks estrogen in some parts of the body.
Compare with estradiol/norethindrone →
cabergoline
Dostinex
Cabergoline is a medicine that helps lower the amount of prolactin in your body.
Compare with estradiol/norethindrone →
clomiphene
Clomid, Serophene
Clomiphene citrate is a medicine that helps women ovulate.
Compare with estradiol/norethindrone →
Compare estradiol/norethindrone vs abiraterone side-by-side →
Medication Guides
Understanding Drug Interactions
How CYP450 enzymes, inhibitors, and inducers affect your medications
Generic vs Brand Name Drugs
FDA requirements, cost savings, and when the difference matters
Narrow Therapeutic Index Drugs
Why some drugs demand precise dosing and monitoring
Common Drug Interactions
Dangerous medication combinations and how to protect yourself
Related Health & Safety Data
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What the FDA Data Shows for estradiol/norethindrone
The FDA label for estradiol/norethindrone (sold under brand names such as Activella, CombiPatch) classifies it as a prescription-only medication in the Estrogen / Progestin Combination class. CombiPatch treats moderate to severe hot flashes caused by menopause. Official labeling lists 11 commonly reported side effects, including Abdominal pain, Back pain, Headache.
Post-market surveillance from the FDA Adverse Event Reporting System (FAERS) captures real-world experience. For this drug, FAERS contains 45,381 voluntary reports. The database also lists 8 documented drug interactions derived from FDA labeling, with the top-flagged interaction rated minor severity. NADAC pricing from CMS.
Report counts do not establish causation — a FAERS entry documents a temporal association, not proof that the drug produced the outcome. Widely prescribed medications naturally accumulate more reports than niche therapies, so raw totals must be interpreted alongside total exposure. Shortage status, recall history, and patent information further shape supply and switching decisions. This page summarizes public FDA data for educational purposes only and is not a substitute for professional medical advice — always consult a licensed healthcare provider before starting, stopping, or changing any medication.
Data Sources
Drug labeling: FDA Drug Labels (SPL/DailyMed). Adverse events: FDA Adverse Event Reporting System (FAERS). Pricing: CMS National Average Drug Acquisition Cost (NADAC).
FAERS reports are voluntary and do not establish causation. Drug interactions are derived from FDA labeling and clinical references. Always consult a healthcare professional before making medication decisions.
Last updated: February 21, 2024
Read our methodology — how this data is sourced, computed, and verified.
All federal data sources used on this page
- FDA Orange Book — approved drug products with therapeutic equivalence. accessdata.fda.gov/cder/ob
- FDA DailyMed — NIH-hosted drug labeling for FDA-approved meds. dailymed.nlm.nih.gov
- FDA Adverse Event Reporting System (FAERS) — post-marketing safety surveillance. fda.gov/drugs/faers
- NLM RxNorm — standardized clinical drug nomenclature. nlm.nih.gov/research/umls/rxnorm
- CMS Medicare Part B Drug Average Sales Price Files — federal drug pricing data. cms.gov/medicare/part-b-drugs/asp
- FDA Drug Shortages Database — current and resolved drug shortage tracking. accessdata.fda.gov/drugshortages