Prescription medicine
Estradiol and norethindrone Brand names: Lopreeza, Combipatch, Activella, Etyqa, Abigale
Estradiol and norethindrone (Combipatch) is a prescription medicine with an FDA approval on record since 1998. FDA's NDC Directory lists it from 7 generic labelers, and pharmacies paid $0.802 per estradiol-noreth 0.5-0.1 mg tablet in the October 7, 2026 NADAC survey; its other strengths are brand-only, $31.79 per patch (Combipatch 0.05-0.25 mg ptch).
- Generic listed
- Boxed warning
Check it at the source: the estradiol and norethindrone FDA label on DailyMed (effective January 16, 2025, Amneal Pharmaceuticals NY LLC); the NDA 20870 record on Drugs@FDA; every estradiol and norethindrone label on DailyMed.
Highlights of the record
FDA label of January 16, 2025; NDC Directory, Drugs@FDA and Orange Book, October 8, 2026; NADAC October 7, 2026
CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER,.
and ENDOMETRIAL CANCER Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions ( 5.1 ), and Clinical Studies ( 14.5 ) ]. The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.5 ), and Clinical Studies ( 14.6 ) ]. Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions ( 5.1 , 5.3 ), and Clinical Studies ( 14.5 , 14.6 ) ]. […]
Used for
From the label: indications and usageLopreeza is indicated for: Lopreeza is an estrogen and progestin combination indicated in a woman with a uterus for: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause (1.1) Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause (1.2) Limitations of Use: When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menop
Forms and strengths
- 0.05 mg / 0.25 mg
- 0.05 mg / 0.14 mg
- 0.5 mg / 0.1 mg
- 0.5 mg / 1 mg
- 1 mg / 0.5 mg
Film-coated tablet; tablet; extended-release patch.
On the market
- Earliest approval on file
- August 7, 1998 Combipatch, Noven Pharms Inc; Drugs@FDA’s file, where older or withdrawn approvals can be missing
- Generic approvals
- 8 first April 17, 2008; 6 with a marketed status in Drugs@FDA
- Labelers listed (NDC)
- 10 of which 7 under generic applications, 3 under brand applications, repackagers included
Supply and safety
- Pharmacy cost (NADAC)
- $0.802 per tablet Estradiol-noreth 0.5-0.1 mg tablet
- Shortage (FDA)
- No current entry
- Recalls by its makers (FDA)
- 4 since 2021 0 Class I among all firms' recalls; latest January 7, 2022
- FAERS reports
- 2,291 through July 30, 2026
What is estradiol and norethindrone used for?
From the label: indications and usageLopreeza is indicated for: Lopreeza is an estrogen and progestin combination indicated in a woman with a uterus for: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause (1.1) Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause (1.2) Limitations of Use: When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products. Prevention of Postmenopausal Osteoporosis (1.3) Limitations of Use: When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. […]
Conditions named in the indications of estradiol and norethindrone's FDA labels, with every medicine labeled for each:
Source: FDA drug label (LOPREEZA), Amneal Pharmaceuticals NY LLC, effective January 16, 2025 (SPL set 966ac064-9eb7-4d15-b271-a7880ed1e79a), via openFDA; the full label on DailyMed
What does the patient leaflet for estradiol and norethindrone say first?
The FDA-approved Medication Guide or Patient Information that comes with the medicine, in its own words.
From the patient leaflet: What is the most important information I should know about Lopreeza (a combination of estrogen and progestin)?Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia (decline of brain function). Taking estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. Taking estrogens with progestins may increase your chance of getting dementia, based on a study of women 65 years of age or older. Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia. Taking estrogen-alone may increase your chance of getting cancer of the uterus (womb). Taking estrogen-alone may increase your chances of getting strokes or blood clots. Taking estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age or older. You and your healthcare provider should talk regularly about whether you still need treatment with Lopreeza.
From the patient leaflet: How should I store Lopreeza?Store Lopreeza at room temperature between 68°F to 77°F (20°C to 25°C). Store Lopreeza in a dry place protected from light. KEEP LOPREEZA and all medicines out of the reach of children.
Source: FDA drug label (Lopreeza), Amneal Pharmaceuticals NY LLC, effective November 30, 2017 (SPL set bf0e39cb-95e7-4831-92d2-0b3f071aeaae), via openFDA; the full label on DailyMed
Is there a generic for estradiol and norethindrone (Combipatch)?
The FDA approved the first generic estradiol and norethindrone on April 17, 2008. 8 generic applications are approved; 6 of them carry a current (not discontinued) marketing status in Drugs@FDA; that status is not evidence that the generic is on sale.
FDA's NDC Directory lists estradiol and norethindrone from 7 labelers under a generic (ANDA) application and from 3 brand labelers. A listing means the company has registered the product for sale; it does not show that every pharmacy stocks it.
- 1998 earliest approval on file
- 2008 first generic approved
- red ticks recalls
Source: Drugs@FDA, FDA NDC Directory and the Orange Book (openFDA bulk files, October 8, 2026)
What do pharmacies pay for estradiol and norethindrone (Combipatch)?
In CMS's NADAC survey of October 7, 2026, pharmacies paid $0.802 per Estradiol-noreth 0.5-0.1 mg tablet, down 9% from $0.884 on October 8, 2025. Prices per unit in the table differ many-fold by strength, form and brand, so compare like with like. The chart's scale runs from the lowest to the highest price shown, not from zero. NADAC is what retail pharmacies paid their wholesalers, per unit, in CMS's monthly survey; what a patient pays depends on insurance and the pharmacy.
- Estradiol-noreth 1-0.5 mg tablet (generic)
- Combipatch 0.05-0.25 mg ptch (brand)
| Strength and form | Brand or generic | Pharmacy cost | 30 tablets, or one pen or vial | 12-month change |
|---|---|---|---|---|
| Abigale 1 mg-0.5 mg tablet | Generic | $0.570 per tablet | $17.09 | -12% |
| Abigale lo 0.5-0.1 mg tablet | Generic | $0.802 per tablet | $24.06 | -9% |
| Estradiol-noreth 0.5-0.1 mg tablet | Generic | $0.802 per tablet | $24.06 | -9% |
| Estradiol-noreth 1-0.5 mg tablet | Generic | $0.570 per tablet | $17.09 | -12% |
| Mimvey 1-0.5 mg tablet | Generic | $0.570 per tablet | $17.09 | -12% |
| Combipatch 0.05-0.14 mg ptch | Brand | $31.84 per patch many times the lowest per-tablet cost; NADAC records the price, not why | n/a | +2% |
| Combipatch 0.05-0.25 mg ptch | Brand | $31.79 per patch many times the lowest per-tablet cost; NADAC records the price, not why | n/a | +2% |
Source: CMS National Average Drug Acquisition Cost (NADAC) survey, October 7, 2026: what retail pharmacies paid per unit; not a counter price
Has estradiol and norethindrone been recalled?
The FDA's Enforcement Report lists 4 recalls naming estradiol and norethindrone since 2021: 0 Class I (the most serious), 2 Class II, 2 Class III; 2 still ongoing. A recall names products and lots, not every product of the medicine.
| Started | Class | Company | Reason |
|---|---|---|---|
| January 7, 2022 | Class III | Teva Pharmaceuticals USA | Mislabeling |
| July 30, 2021 | Class II | Noven Pharmaceuticals Inc | Failed Stability Specifications; out of specification for shear. |
Source: FDA Enforcement Report (drug recalls) via openFDA, through October 8, 2026
What does the estradiol and norethindrone label say about other medicines?
The estradiol and norethindrone label names 15 other medicines in its interaction, contraindication or warning sections. The labels of 3 other medicines name estradiol and norethindrone. The sentences are the labels' own; a label lists what its studies and reports found, not every interaction.
| Medicine named | Section | What the label says |
|---|---|---|
| Carbamazepine | drug interactions | Inducers of CYP3A4 such as St. John’s wort ( Hypericum perforatum ) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. |
| Clarithromycin | drug interactions | Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and result in adverse reactions. |
| Efavirenz | drug interactions | Inducers of CYP3A4 such as St. 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 … |
| Erythromycin | drug interactions | Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and result in adverse reactions. |
| Itraconazole | drug interactions | Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and result in adverse reactions. |
| Ketoconazole | drug interactions | Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and result in adverse reactions. |
| Medroxyprogesterone | boxed warning | … years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions ( 5.1 ), and Clinical Studies ( 14.5 ) ]. |
| Nelfinavir | 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. |
| Nevirapine | drug interactions | Inducers of CYP3A4 such as St. 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 … |
| Phenobarbital | drug interactions | Inducers of CYP3A4 such as St. John’s wort ( Hypericum perforatum ) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. |
| Phenytoin | drug interactions | Inducers of CYP3A4 such as St. 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 … |
| Rifabutin | drug interactions | Inducers of CYP3A4 such as St. 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 … |
| Rifampin | drug interactions | Inducers of CYP3A4 such as St. John’s wort ( Hypericum perforatum ) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. |
| Ritonavir | drug interactions | Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and result in adverse reactions. |
Every other medicine the estradiol and norethindrone label names
| Medicine named | Section | What the label says |
|---|---|---|
| Testosterone | warnings and precautions | Free hormone concentrations, such as testosterone and estradiol, may be decreased. |
Other labels that name estradiol and norethindrone
Source: FDA drug label (LOPREEZA), Amneal Pharmaceuticals NY LLC, effective January 16, 2025 (SPL set 966ac064-9eb7-4d15-b271-a7880ed1e79a), via openFDA; the full label on DailyMed
What do FAERS reports show for estradiol and norethindrone?
The FDA Adverse Event Reporting System holds 2,291 reports that list estradiol and norethindrone among the medicines taken, through July 30, 2026, each a report of something that happened, not proof the medicine caused it; 43 are coded as a death and 464 as a hospital stay. Counts follow how widely a medicine is used and watched, and they are not a measure of how risky it is.
Reports received each year
The most reported reactions
Source: FDA Adverse Event Reporting System (FAERS) via openFDA, reports through July 30, 2026
What else is labeled for the same conditions as estradiol and norethindrone?
5 other medicines are given the same way (oral) and in the same FDA class as estradiol and norethindrone or labeled mainly for the same use (menopause symptoms), the same class first. Menopause symptoms lists all 11 medicines labeled for it, by any route. They are listed as records, not as substitutes: whether one can replace another is a prescriber's decision.
| Medicine | Shared indication | Generic labelers (oral) | Pharmacy cost | Shortage |
|---|---|---|---|---|
| Estrogens conjugated | Osteoporosis, Menopause symptoms | 1 labeler | $5.47 per tablet 0.625 mg tablet | No current entry |
| Bazedoxifene and estrogens conjugated | Osteoporosis | none listed | $6.48 per tablet 0.45-20 mg tablet | No current entry |
| Fezolinetant | Menopause symptoms | none listed | $18.58 per tablet 45 mg tablet | No current entry |
| Elinzanetant | Menopause symptoms | none listed | $9.97 per capsule 60 mg capsule | No current entry |
| Ospemifene | Menopause symptoms | none listed | $8.17 per tablet 60 mg tablet | No current entry |
Every medicine labeled for the same conditions as estradiol and norethindrone
Source: FDA drug labels (indications), NDC Directory, NADAC of October 7, 2026, FDA shortages (October 8, 2026)
What next?
- Alternatives to estradiol and norethindrone
- 5 medicines for the same use
- Other estrogens
- the pharmacologic class, with prices and generics
- Estradiol and norethindrone side effects
- the label's list beside FAERS reports
- Check an interaction
- what two or more labels say about each other