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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 →

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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.

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.

This is a plain-language summary of estradiol/norethindrone's FDA labeling, not individualized dosing advice. Ask a pharmacist or prescriber before changing how you take this medication.

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.

This is a plain-language summary of estradiol/norethindrone's FDA labeling, not individualized advice. Ask a pharmacist or prescriber about pregnancy or breastfeeding on this medication.

Missed Dose

Apply a new patch as soon as you remember. Then, change your patch on your regular schedule.

This is a plain-language summary of estradiol/norethindrone's FDA labeling, not individualized advice. Ask a pharmacist or prescriber what to do about your specific missed dose.

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 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.

What to do: Your doctor should monitor you for side effects and may need to adjust your hormone dose.

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.

What to do: Your doctor may need to adjust your dose or check if the medication is still working correctly.

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.

What to do: Tell your doctor if you experience new side effects, as they may need to change your dosage.

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.

What to do: Your healthcare provider may need to monitor you closely or adjust your medication levels while you are taking both drugs.

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.

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.

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This is a plain-language summary of interactions documented in FDA labeling, not individualized advice. Ask a pharmacist or prescriber before combining medications.

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 most commonly reported side effects of estradiol/norethindrone include Abdominal pain, Back pain, Headache, Nausea, Breast pain. Based on 37,523 FDA adverse event reports. Always consult your healthcare provider about potential side effects.
Does estradiol/norethindrone interact with other medications?
Yes, estradiol/norethindrone has 8 known drug interactions. Notable interactions include ketoconazole, carbamazepine, erythromycin. Always inform your doctor about all medications you are taking.
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.
Is estradiol/norethindrone safe during pregnancy?
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. Always consult your healthcare provider before using any medication during pregnancy or breastfeeding.

Related Medications in Estrogen / Progestin Combination

Other drugs grouped near estradiol/norethindrone - same-class peers and common alternatives.

abiraterone

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anastrozole

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bazedoxifene/conjugated estrogens

Duavee

Duavee is a combination medicine containing estrogen and a drug that blocks estrogen in some parts of the body.

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cabergoline

Dostinex

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clomiphene

Clomid, Serophene

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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 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 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.

Data currency: FDA FAERS adverse-event reports through 2025, CMS NADAC acquisition-cost pricing effective December 2024, compiled and last refreshed May 2026. See our methodology for per-source dates and refresh cadence. Spot a figure that looks wrong? Report a correction.

All federal data sources used on this page