Prescription medication · Estrogen / Progestin Combination

estradiol/norethindrone

Also sold as Activella, CombiPatch. CombiPatch treats moderate to severe hot flashes caused by menopause.

Data updated 2026-05-15

37,523
FDA reports
8
InteractionsFew interactions
$29.78
Brand price (NADAC)

What the data shows

estradiol/norethindrone (Activella) is a prescription Estrogen / Progestin Combination, with 37,523 FDA adverse-event reports on file, with 8 documented drug interactions.

Reporting volume reflects how widely a drug is used and studied, not how dangerous it is, a FAERS report documents a temporal association, never proof of cause.

estradiol/norethindrone (Activella) is a prescription Estrogen / Progestin Combination. CombiPatch treats moderate to severe hot flashes caused by menopause.

CombiPatch is a skin patch that contains estrogen and progestin hormones. It is used to treat menopause symptoms and conditions caused by low estrogen.

Verify with FDA → · CMS NADAC pricing →

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 →

Compare with Another Drug →

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.

The sections below are summarized in plain English from estradiol/norethindrone's FDA-approved prescribing information. They describe what the official label says, and are not personal medical advice.

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.

Side Effects (from patient reports)

Based on 37,523 FDA adverse event reports.

Most-reported reactions

Adverse reactions in FAERS for estradiol/norethindrone, by number of reports

reports

What this shows Bars show how often each reaction was reported, not how likely it is to happen, a report records a temporal association, never proof that the drug caused it.

Source FDA Adverse Event Reporting System (FAERS)

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

minor ketoconazole

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.

minor carbamazepine

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.

minor erythromycin

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.

minor clarithromycin

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.

minor rifampin

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.

Check all your medications →

This is a plain-language summary of FDA-label interaction records and does not provide individual medication-combination directions.

Common Questions

Can CombiPatch prevent heart disease?
No, CombiPatch should not be used to prevent heart disease.
Can CombiPatch prevent dementia?
No, CombiPatch should not be used to prevent dementia.
What should I do if the patch falls off?
If the patch falls off, apply a new patch to a different area of your lower abdomen.
Can I use CombiPatch if I have a history of blood clots?
You should not use CombiPatch if you have a history of blood clots.
Can I use CombiPatch if I have liver problems?
You should not use CombiPatch if you have liver problems.
How often should I change the CombiPatch?
Change the CombiPatch twice a week, every 3 to 4 days.
Where should I apply the CombiPatch?
Apply the CombiPatch to your lower abdomen.
What if I experience irregular bleeding?
Irregular bleeding may occur, especially in the first 6 months. It usually decreases over time.
Can I use CombiPatch if I have breast cancer?
You should not use CombiPatch if you have or had breast cancer.
What should I do if I have abnormal vaginal bleeding?
Tell your doctor right away if you have any undiagnosed abnormal vaginal bleeding.
What are the common side effects of estradiol/norethindrone?
The registry lists Abdominal pain, Back pain, Headache, Nausea, Breast pain among the most-reported FAERS reaction terms for estradiol/norethindrone. The compiled record contains 37,523 FDA adverse-event reports. These counts are not an individual symptom assessment.
Does estradiol/norethindrone interact with other medications?
The registry has 8 documented interaction rows for estradiol/norethindrone. Notable source-record pairings include ketoconazole, carbamazepine, erythromycin. These rows are not a complete medication review.
What drug class is estradiol/norethindrone?
estradiol/norethindrone belongs to the Estrogen / Progestin Combination drug class. It requires a prescription (Rx). CombiPatch treats moderate to severe hot flashes caused by menopause.
What pregnancy or breastfeeding source fields are listed for estradiol/norethindrone?
The FDA label for estradiol/norethindrone contains product-specific pregnancy or breastfeeding language. PlainMeds does not apply that source text to an individual.

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

FDA bioequivalence and label-record context for narrow therapeutic index medicines

Common Drug Interactions

Dangerous medication combinations and how to protect yourself

Save on estradiol/norethindrone

Compare prices and find discounts at pharmacies near you. Free coupons can save up to 80% on prescriptions.

Check Prices on GoodRx →

Disclosure: This link may earn us a commission at no extra cost to you. See our terms.

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 37,523 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 are separate source-record fields. This page is a public FDA/CMS registry and does not provide medical, treatment, substitution, or medication-change directions.

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. This registry does not provide medication decisions.

Last updated: February 21, 2024

PlainMeds is rendered directly from FDA openFDA/FAERS extracts, DailyMed labels, and CMS drug-pricing files, no number is typed in by an editor. FAERS counts, recalls, shortages, and price figures on this page are queried live from those federal extracts. See our editorial standards & corrections policy, the methodology behind these numbers, or report a data error. Data current as of 2026-05-15. Primary sources: openFDA / FAERS, DailyMed and CMS Part B ASP.

Read our methodology - how this data is sourced, computed, and verified.

Data currency: FDA FAERS adverse-event reports through 2025, CMS NADAC acquisition-cost pricing effective December 2024, compiled from the source snapshot dated . See our methodology for per-source dates and refresh cadence. Spot a figure that looks wrong? Report a data issue.

All federal data sources used on this page