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Norethindrone Acetate and Ethinyl Estradiol .5 mg; .0025 mg Tablet, 84-count — NDC 75834-129-29 (Billing 75834-0129-29)

by Nivagen Pharmaceuticals, Inc. · 3 BLISTER PACK in 1 CARTON / 28 TABLET in 1 BLISTER PACK

This is a package of 84 tablets of Norethindrone Acetate and Ethinyl Estradiol .5 mg; .0025 mg Tablet from Nivagen Pharmaceuticals, Inc., no longer marketed (first marketed Nov 2016), no longer in the FDA NDC Directory; retail pharmacies pay about $1.37 per tablet (NADAC). It is the main listing for this product, which comes in 2 package sizes.

NDC 75834-0129-29
🏷️ FDA NDC (as labeled) 75834-129-29 billing pads the product segment with a zero
This package
Contains84-count Cost per ea$1.37 NADAC Per package$114.92 / 84 tablets Pack sizes2 compare ↓
Also priced by: Part D plans $1.84/unit — full pricing hub ↓
Main listing for product 75834-129 · Also comes in: 90 tablets 75834-129-90
Rx only Generic Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Aug 27, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Oct 2021. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 75834-129-29
Product NDC 75834-129
11-digit billing NDC 75834012929
NCPDP billing unit EA — each (per item)
RxCUI 1090992, 1251323, 1251334, 1251336
UNII 423D2T571U, 9S44LIC7OJ
Application # ANDA203435
SPL Set ID 2c2a37e1-adaf-4947-abb1-736bfa58bf98
Established class (EPC) Estrogen
Mechanism of action Estrogen Receptor Agonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Oct 2021)
Marketing start 2016-11-25
Route ORAL
Dosage form TABLET
Substance NORETHINDRONE ACETATE; ETHINYL ESTRADIOL
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 24993002250305
GPI class Norethindrone-Eth Estradiol
GCN Seq No 049858
GCN 15567
HICL code 001455
Ingredient (HICL) Norethindrone Ac/Eth Estradiol
HIC1 code G
Therapeutic class — broad (HIC1) Female Genital System
HIC2 code G1
Therapeutic class — intermediate (HIC2) Estrogens
HIC3 code G1A
Therapeutic class — specific (HIC3) Estrogenic Agents
AHFS code 68:16.04.00
AHFS class Estrogens
FDB label name NORETHIND-ETH ESTRAD 0.5-2.5
FDB brand name Norethindron-Ethinyl Estradiol
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 049858
  • GCN: 15567
  • GPI-14 (Medi-Span): 24993002250305
  • HICL (First Databank): 001455
  • AHFS class code: 68:16.04.00
  • RxCUI (RxNorm): 1090992
Why two NDCs? The FDA registers this code as 75834-129-29 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 75834-0129-29. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Estrogen class.

Pharmacologic class Estrogen
Drug family (ATC) Progestogens and estrogens, sequential preparations, Natural and semisynthetic estrogens, plain, Estrogens
How it works Estrogen Receptor Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name NORETHIND-ETH ESTRAD 0.5-2.5 Ingredient Norethindrone Ac/Eth Estradiol
📖 What it is MedlinePlus · NLM

Oral contraceptives (birth-control pills) containing ethinyl estradiol (an estrogen) and norethindrone (a progestin) are used to prevent pregnancy. Estrogen and progestin are two female sex hormones. Combinations of estrogen and progestin work mainly by preventing ovulation (the release of eggs from the ovaries). Oral contraceptives are an effective method of birth control, but they do not prevent the spread of human immunodeficiency virus (HIV, the virus that causes acquired immunodeficiency syndrome [AIDS]) and other sexually transmitted diseases.

Read the full MedlinePlus article ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $1.368 $114.92 / 84 tablets
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $1.84 $154.38 / 84 tablets
NADAC price history (per ea) — tap or hover for the price & month
Dec 2021 Mar 2022 Jun 2022 Nov 2022 $2.062 $1.154
▼ Down 19% over the last 11 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startMarketing endStatus
75834-0129-29 You're viewing this Main listing 3 BLISTER PACK in 1 CARTON / 28 TABLET in 1 BLISTER PACK $1.37 / ea $114.92 2016-11-25 — Discontinued by firm
75834-0129-90 75834-129-90 90 TABLET in 1 BOTTLE — — 2016-11-25 — Discontinued by firm

Pack size FAQ

What quantity is in this package?
This is a 84-count package — 3 blister pack in 1 carton / 28 tablet in 1 blister pack.
How does this package differ from NDC 75834-0129-90?
Both are Norethindrone Acetate and Ethinyl Estradiol .5 mg; .0025 mg Tablet — the drug itself is identical. This page's package is the 84-count one, while NDC 75834-0129-90 is the 90 tablets package.
What NDC number is used to bill for this package of Norethindrone Acetate and Ethinyl Estradiol .5 mg; .0025 mg Tablet?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Fyavolv .0025 mg/1; .5 mg 68180-0827-73 Lupin 28 tablets $0.913 AB Availability likely save 33%
Norethindrone Acetate and Ethinyl Estradiol .5 mg/1; 2.5 ug 68462-0656-29 Glenmark 84 tablets $0.913 AB Availability likely save 33%
Norethindrone Acetate and Ethinyl Estradiol .5 mg/1; .0025 mgthis 75834-0129-29 Nivagen 84 tablets $1.368 AB Discontinued —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2016
On the market since
Nov 2016
📍
2026
Currently FDA-listed
10 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerNivagen Pharmaceuticals, Inc.
Application holderNOVAST LABORATORIES LTD
FDA applicationANDA203435 (ANDA)
Labeler code75834
First marketedNov 2016
Product typeHuman Prescription Drug
Portfolio95 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~3 min read ▾

WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER AND PROBABLE DEMENTIA WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER AND PROBABLE DEMENTIA See full prescribing information for complete boxed warning. Estrogen Plus Progestin Therapy Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 ) The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) ( 5.1 ) The WHI estrogen plus progestin substudy reported an increased risk of invasive breast cancer ( 5.2 ) The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older ( 5.3 ) Estrogen-Alone Therapy There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens ( 5.2 ) Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 ) The WHI estrogen-alone substudy reported increased risks of stroke and DVT ( 5.1 ) The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older ( 5.3 ) Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.3) , and Clinical Studies (14.5 , 14.6) ] .

The Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk 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 estrogens (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 or 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) ] . Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.2) , and Clinical Studies (14.5) ] . In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.

Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ] . Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.3) , and Clinical Studies (14.5 , 14.6) ] . The WHI estrogen-alone substudy reported increased risks of stroke and DVT in pos… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage 90 words ▾

1 INDICATIONS AND USAGE Norethindrone acetate and Ethinyl estradiol tablets are an estrogen plus progestin indicated in a woman with a uterus for: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) Prevention of Postmenopausal Osteoporosis ( 1.2 )

1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

1.2Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be condisered for women at significant risk of osteoporosis and non-estrogen medication should be carefully considered.

⏱️ Dosage and Administration 112 words ▾

2 DOSAGE AND ADMINISTRATION Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. One tablet taken orally once daily ( 2.1 , 2.2 )

2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Norethindrone acetate and ethinyl estradiol tablets therapy consists of a single tablet to be taken orally once daily.

2.2Prevention of Postmenopausal Osteoporosis Norethindrone acetate and ethinyl estradiol tablets therapy consists of a single tablet taken orally once daily.

💊 Dosage Forms and Strengths 98 words ▾

3 DOSAGE FORMS AND STRENGTHS The following two strengths of norethindrone acetate and ethinyl estradiol tablets are available: 0.5 mg/2.5 mcg: Each round light yellow tablet contains 0.5 mg norethindrone acetate and 2.5 mcg ethinyl estradiol; debossed with N1 on one side. 1 mg/5 mcg: Each round white tablet contains 1 mg norethindrone acetate and 5 mcg ethinyl estradiol; debossed with N2 on one side. Round light yellow tablet contains 0.5 mg norethindrone acetate and 2.5 mcg ethinyl estradiol ( 3 ) Round white tablet contains 1 mg norethindrone acetate and 5 mcg ethinyl estradiol ( 3 )

⛔ Contraindications 204 words ▾

4 CONTRAINDICATIONS Norethindrone acetate and ethinyl estradiol tablets are contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding Known, suspected, or history of breast cancer Known or suspected estrogen-dependent neoplasia Active DVT, PE or a history of these conditions Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions Known anaphylactic reaction or angioedema to Norethindrone acetate and Ethinyl estradiol tablets. Known liver impairment or disease Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders Known or suspected pregnancy Undiagnosed abnormal genital bleeding ( 4 ) Known, suspected, or history of breast cancer ( 4 , 5.2 ) Known or suspected estrogen-dependent neoplasia ( 4 , 5.2 ) Active DVT, PE, or history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions ( 4 , 5.1 ) Known anaphylactic reaction or angioedema to norethindrone acetate and ethinyl estradiol tablets.

( 4 ) Known liver impairment or disease ( 4 , 5.10 ) Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 ) Known or suspected pregnancy ( 4 , 8.1 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Estrogens increase the risk of gallbladder disease ( 5.4 ) Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.5 , 5.6 , 5.9 , 5.10 ) Monitor thyroid function in women on thyroid replacement therapy ( 5.11 , 5.18 )

5.1Cardiovascular Disorders An increased risk of PE, DVT, stroke, and MI has been reported with estrogen plus progestin therapy. An increased risk of stroke and DVT has been reported with estrogen-alone therapy. Should any of these occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately.

Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. Stroke In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years) [see Clinical Studies (14.5) ].

The increase in risk was demonstrated after the first year and persisted. 1 Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily conjugated estrogens CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years).

The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies (14.5) ] . Should a stroke occur or be suspected, estrogen-alone therapy should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years).

1 Coronary Heart Disease In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). 1 An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 [see Clinical Studies (14.5) ].

In the WHI estrogen-alone substudy, no overall effect on CHD events was reported in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies (14.5) ]. Subgroup analyses of women 50 to 59 years of age suggest a statistically non-significant reduction in CHD events (CE [0.625 mg]-alone compared to placebo) in women with less than 10 years since menopause (8 versus 16 per 10,000 woman-years). 1 In postmenopausal women with documented heart disease (n = 2,763), average 66.7 years of age, in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study [HERS]), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit.

During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established CHD. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand, three hundred and twenty-one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II.

Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning , Warnings and Precautions (5.1) ]. Malignant Neoplasms [ see Boxed Warning , Warnings and Precautions (5.2) ]. Most common adverse reactions (incidence greater than or equal to 5 percent) are headache, abdominal pain, breast pain, and edema (generalized).

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Nivagen Pharmaceuticals Toll-free at 1-877-977-0687 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions reported by ≥5 percent of subjects in controlled clinical studies of norethindrone acetate and ethinyl estradiol tablets are shown in Table 1. Table 1.

Associated Adverse Reactions Reported by ≥ 5 Percent of Subjects by Body System The total number of subjects for each body system may be less than the number of subjects with AEs in that body system because a subject may have had more than one AE per body system BODY SYSTEM/ Adverse Reaction Number (Percent) of Subjects Placebo N = 247 NDAc-EE 0.5/2.5 NDAc-EE 0.5/2.5 = Norethindrone Acetate - Ethinyl Estradiol 0.5 mg/2.5 mcg NDAc-EE 1/5 = Norethindrone Acetate - Ethinyl Estradiol 1 mg/5 mcg N = 244 NDAc-EE 1/5 N = 258 BODY AS A WHOLE 23 (12.8) 30 (16.9) 30 (15.7) Edema – Generalized 10 (4.0) 12 (4.9) 11 (4.3) Headache 12 (4.9) 14 (5.7) 16 (6.2) DIGESTIVE SYSTEM 8 (4.4) 17 (9.6) 25 (13.1) Abdominal Pain 3 (1.2) 13 (5.3) 14 (6.8) UROGENITAL SYSTEM 20 (11.1) 34 (19.2) 45 (23.6) Breast Pain 9 (3.6) 22 (9.0) 20 (7.8)

6.2Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of norethindrone acetate and ethinyl estradiol tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Genitourinary System Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; increase in size of uterine leiomyomata, vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer; uterine cancer; vaginal hemorrhage; ovarian cyst; irregular menstruation; metrorrhagia; menorrhagia; dysmenorrhea; uterine enlargement.

Breasts Tenderness, enlargement, breast pain, nipple pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer; breast disorder; breast mass; breast enlargement. Cardiovascular Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; thrombosis; chest pain; myocardial infarction; cerebrovascular accident (stroke); transient ischemic attack; hemiparesis; increase in blood pressure; irregular heart rate; palpitations; dyspnea. Gastrointestinal Nausea, vomiting; cholestatic jaundice; pancreatitis, enlargement of hepatic hemangiomas; bloating, abdominal cramps; abdominal pain; increased incidence of gallbladder disease; cholecystitis; cholelithiasis.

Skin Chloasma or melasma that may persist when drug is discontinued; generalized erythema; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; rash, pruritus. Eyes Retinal vascular thrombosis; visual impairment; intolerance to contact lenses. Central Nervous System (CNS) Headache; migraine; dizziness; depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia; paresthesia; insomnia.

Miscellaneous Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgias; leg… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS No drug-drug interaction studies have been conducted for norethindrone acetate and ethinyl estradiol tablets . Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism ( 7.1 )

7.1Effect of Other Drugs on Combined Hormonal Products Substances decreasing or increasing the plasma concentration of estrogen: In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St.

John's wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine and rifampin may decrease the plasma concentration of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase the plasma concentration of estrogens and may result in side effects. Co-administration of atorvastatin and certain hormonal products containing ethinyl estradiol increase AUC values for ethinyl estradiol approximately 20 percent.

Ascorbic acid and acetaminophen may increase the plasma ethinyl estradiol concentration, possibly by inhibition of conjugation.

7.2Effect of Combined Hormonal Products on Other Drugs Combination hormonal products containing some synthetic estrogens (for example, ethinyl estradiol) may inhibit the metabolism of other compounds. Combination hormonal products have been shown to significantly decrease the plasma concentration of lamotrigine likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS Nursing Mothers: Estrogen administration to nursing women has been shown to decrease the quantity and quality of breast milk ( 8.3 ) Geriatric Use: An increased risk of probable dementia in women over 65 years of age was reported in the Women's Health Initiative Memory ancillary studies of the Women's Health Initiative ( 5.3 , 8.5 )

8.1Pregnancy Norethindrone acetate and ethinyl estradiol tablets should not be used during pregnancy [see Contraindications (4) ]. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy.

8.3Nursing Mothers Norethindrone acetate and ethinyl estradiol tablets should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogen and progestin have been identified in the breast milk of women receiving estrogen plus progestin therapy.

Caution should be exercised when norethindrone acetate and ethinyl estradiol tablets are administered to a nursing woman.

8.4Pediatric Use Norethindrone acetate and ethinyl estradiol tablets are not indicated in children. Clinical studies have not been conducted in the pediatric population.

8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing norethindrone acetate and ethinyl estradiol tablets to determine whether those over 65 years of age differ from younger subjects in their response to norethindrone acetate and ethinyl estradiol tablets. The Women's Health Initiative Studies In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies (14.5) ].

In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [ see Clinical Studies (14.5) ] . The Women's Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen plus progestin or estrogen-alone when compared to placebo [see Warnings and Precautions (5.3) , and Clinical Studies (14.6) ].

Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [ see Warnings and Precautions (5.3) , and Clinical Studies (14.6) ].

8.6Renal Impairment The effect of renal impairment on the pharmacokinetics of norethindrone acetate and ethinyl estradiol tablets have not been studied.

8.7Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of norethindrone acetate and ethinyl estradiol tablets have not been studied.

🤰 Pregnancy 49 words ▾

8.1Pregnancy Norethindrone acetate and ethinyl estradiol tablets should not be used during pregnancy [see Contraindications (4) ]. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy.

🧒 Pediatric Use 24 words ▾

8.4Pediatric Use Norethindrone acetate and ethinyl estradiol tablets are not indicated in children. Clinical studies have not been conducted in the pediatric population.

🧓 Geriatric Use 218 words ▾

8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing norethindrone acetate and ethinyl estradiol tablets to determine whether those over 65 years of age differ from younger subjects in their response to norethindrone acetate and ethinyl estradiol tablets. The Women's Health Initiative Studies In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Clinical Studies (14.5) ].

In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [ see Clinical Studies (14.5) ] . The Women's Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen plus progestin or estrogen-alone when compared to placebo [see Warnings and Precautions (5.3) , and Clinical Studies (14.6) ].

Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [ see Warnings and Precautions (5.3) , and Clinical Studies (14.6) ].

🆘 Overdosage 44 words ▾

10 OVERDOSAGE Overdosage of estrogen plus progestin may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of norethindrone acetate and ethinyl estradiol tablets with institution of appropriate symptomatic care.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.

After menopause, most endogenous estrogen is produced by conversion of androstenedione, which is secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. The pharmacologic effects of ethinyl estradiol are similar to those of endogenous estrogens.Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.

To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue.Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.Progestin compounds enhance cellular differentiation and generally oppose the actions of estrogens by decreasing estrogen receptor levels, increasing local metabolism of estrogens to less active metabolites, or inducing gene products that blunt cellular responses to estrogen.

Progestins exert their effects in target cells by binding to specific progesterone receptors that interact with progesterone response elements in target genes. Progesterone receptors have been identified in the female reproductive tract, breast, pituitary, hypothalamus, bone, skeletal tissue and central nervous system. Progestins produce similar endometrial changes to those of the naturally occurring hormone progesterone.

12.2Pharmacodynamics Currently, there are no pharmacodynamic data known for norethindrone acetate and ethinyl estradiol tablets.

12.3Pharmacokinetics Absorption Norethindrone acetate (NA) is completely deacetylated to norethindrone after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate and ethinyl estradiol (EE) are absorbed from norethindrone acetate and ethinyl estradiol tablets, with maximum plasma concentrations of norethindrone and ethinyl estradiol generally occurring 1 to 2 hours postdose. Both are subject to first-pass metabolism after oral dosing, resulting in an absolute bioavailability of approximately 64 percent for norethindrone and 55 percent for ethinyl estradiol.

Bioavailability of norethindrone acetate and ethinyl estradiol tablets is similar to that from solution for norethindrone and slightly less for ethinyl estradiol. Administration of norethindrone acetate and ethinyl estradiol tablets with a high fat meal decreases rate but not extent of ethinyl estradiol absorption. The extent of norethindrone absorption is increased by 27 percent following administration of norethindrone acetate and ethinyl estradiol tablets with food.

The full pharmacokinetic profile of norethindrone acetate and ethinyl estradiol tablets was not characterized due to assay sensitivity limitations. However, the multiple-dose pharmacokinetics were studied at a dose of 1 mg NA/10 mcg EE in 18 postmenopausal women. Mean plasma concentrations are shown below (Figure 1) and pharmacokinetic parameters are found in Table 2.

Based on a population pharmacokinetic analysis, mean steady-state concentrations of norethindrone for 1 mg NA/5 mcg EE and 1/10 are slightly more than proportional to dose when compared to 0.5 mg NA/2.5… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action ~1 min read ▾

12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.

After menopause, most endogenous estrogen is produced by conversion of androstenedione, which is secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. The pharmacologic effects of ethinyl estradiol are similar to those of endogenous estrogens.Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.

To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue.Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.Progestin compounds enhance cellular differentiation and generally oppose the actions of estrogens by decreasing estrogen receptor levels, increasing local metabolism of estrogens to less active metabolites, or inducing gene products that blunt cellular responses to estrogen.

Progestins exert their effects in target cells by binding to specific progesterone receptors that interact with progesterone response elements in target genes. Progesterone receptors have been identified in the female reproductive tract, breast, pituitary, hypothalamus, bone, skeletal tissue and central nervous system. Progestins produce similar endometrial changes to those of the naturally occurring hormone progesterone.

📦 How Supplied / Storage and Handling 192 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Norethindrone acetate and ethinyl estradiol tablets are available in the following strength and package sizes: 1. 75834-129-84 Blister card of 28 round light yellow tablets with 0.5 mg norethindrone acetate and 2.5 mcg ethinyl estradiol 2. 75834-129-29 Carton containing 3 × 28 tablet blister cards each in a plastic compact.

Each blister card contains 28 round light yellow tablets with 0.5 mg norethindrone acetate and 2.5 mcg ethinyl estradiol 3. 75834-129-90 Bottle of 90 round light yellow tablets with 0.5 mg norethindrone acetate and 2.5 mcg ethinyl estradiol 4. 75834-130-84 Blister card of 28 round white tablets with 1 mg norethindrone acetate and 5 mcg ethinyl estradiol 5.

75834-130-29 Carton containing 3 × 28 tablet blister cards each in a plastic compact. Each blister card contains 28 round white tablets with 1 mg norethindrone acetate and 5 mcg ethinyl estradiol 6. 75834-130-90 Bottle of 90 round white tablets with 1 mg norethindrone acetate and 5 mcg ethinyl estradiol.

16.2Storage and Handling Store at 20º-25º C (68º-77º F); excursions permitted to 15 to 30º C (59 to 86º F) [see USP Controlled Room Temperature].

📦 Storage and Handling 26 words ▾

16.2Storage and Handling Store at 20º-25º C (68º-77º F); excursions permitted to 15 to 30º C (59 to 86º F) [see USP Controlled Room Temperature].

📋 Description 165 words ▾

11 DESCRIPTION Norethindrone acetate and ethinyl estradiol tablets are a continuous dosage regimen of a progestin-estrogen combination for oral administration. The following two strengths of norethindrone acetate and ethinyl estradiol tablets are available: 0.5 mg/2.5 mcg: Each round light yellow tablet contains 0.5 mg norethindrone acetate and 2.5 mcg ethinyl estradiol; debossed with N1 on one side. 1 mg/5 mcg: Each round white tablet contains 1 mg norethindrone acetate and 5 mcg ethinyl estradiol; debossed with N2 on one side.

Each white tablet also contains lactose monohydrate, pregelatinized starch, polyethylene glycol, magnesium stearate, ethyl cellulose, vitamin E, titanium dioxide, hypromelloses, macrogol/PEG, triacetin, polydextrose. Each light yellow tablet also contains lactose monohydrate, pregelatinized starch, polyethylene glycol, magnesium stearate, ethyl cellulose, vitamin E, iron oxide yellow, iron oxide black, talc, polyvinyl alcohol, titanium dioxide, lecithin (soya). The structural formulas are as follows.

Norethindrone Acetate [19-Norpregn-4-en-20-yn-3-one, 17-(acetyloxy)-, (17α)-]; Molecular Weight: 340.47 Molecular Formula: C22H28O3 Ethinyl Estradiol [19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17α)-]; Molecular Weight: 296.41 Molecular Formula: C20H24O2 Chemical Structure Chemical Structure

💬 Information for Patients 120 words ▾

17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information)

17.1Abnormal Vaginal Bleeding Inform postmenopausal women of the importance of reporting abnormal vaginal bleeding to their healthcare provider as soon as possible [ see Warnings and Precautions (5.2) ].

17.2Possible Serious Adverse Reactions with Estrogen Plus Progestin Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen plus progestin therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions (5.1 , 5.2 , 5.3) ].

17.3Possible Less Serious but Common Adverse Reactions with Estrogen Plus Progestin Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen plus progestin therapy such as headache, breast pain and tenderness, nausea and vomiting.

🍼 Nursing Mothers 70 words ▾

8.3Nursing Mothers Norethindrone acetate and ethinyl estradiol tablets should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogen and progestin have been identified in the breast milk of women receiving estrogen plus progestin therapy.

Caution should be exercised when norethindrone acetate and ethinyl estradiol tablets are administered to a nursing woman.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption Norethindrone acetate (NA) is completely deacetylated to norethindrone after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate and ethinyl estradiol (EE) are absorbed from norethindrone acetate and ethinyl estradiol tablets, with maximum plasma concentrations of norethindrone and ethinyl estradiol generally occurring 1 to 2 hours postdose. Both are subject to first-pass metabolism after oral dosing, resulting in an absolute bioavailability of approximately 64 percent for norethindrone and 55 percent for ethinyl estradiol.

Bioavailability of norethindrone acetate and ethinyl estradiol tablets is similar to that from solution for norethindrone and slightly less for ethinyl estradiol. Administration of norethindrone acetate and ethinyl estradiol tablets with a high fat meal decreases rate but not extent of ethinyl estradiol absorption. The extent of norethindrone absorption is increased by 27 percent following administration of norethindrone acetate and ethinyl estradiol tablets with food.

The full pharmacokinetic profile of norethindrone acetate and ethinyl estradiol tablets was not characterized due to assay sensitivity limitations. However, the multiple-dose pharmacokinetics were studied at a dose of 1 mg NA/10 mcg EE in 18 postmenopausal women. Mean plasma concentrations are shown below (Figure 1) and pharmacokinetic parameters are found in Table 2.

Based on a population pharmacokinetic analysis, mean steady-state concentrations of norethindrone for 1 mg NA/5 mcg EE and 1/10 are slightly more than proportional to dose when compared to 0.5 mg NA/2.5 mcg EE tablets. It can be explained by higher SHBG concentrations. Mean steady-state plasma concentrations of ethinyl estradiol for the norethindrone acetate and ethinyl estradiol 0.5/2.5 tablets and norethindrone acetate and ethinyl estradiol 1/5 tablets are proportional to dose, but there is a less than proportional increase in steady-state concentrations for the NA/EE 1/10 tablet.

Figure 1. Mean Steady-State (Day 87) Plasma Norethindrone and Ethinyl Estradiol Concentrations Following Continuous Oral Administration of 1 mg NA/10 mcg EE Tablets Table 2: Mean (SD) Single-Dose (Day 1) and Steady-State (Day 87) Pharmacokinetic Parameters C max = Maximum plasma concentration; T max = Time of Cmax; AUC (0-24) = Area under the plasma concentration-time curve over the dosing interval; and CL/F = Apparent oral clearance; t½ = Elimination half-life Following Administration of 1 mg NA/10 mcg EE Tablets C max t max AUC (0-24) CL/F t½ Norethindrone ng/mL hr ng.hr/mL mL/min hr Day 1 6.0 (3.3) 1.8 (0.8) 29.7 (16.5) 588 (416) 10.3 (3.7) Day 87 10.7 (3.6) 1.8 (0.8) 81.8 (36.7) 226 (139) 13.3 (4.5) Ethinyl Estradiol pg/mL hr pg.hr/mL mL/min hr Day 1 33.5 (13.7) 2.2 (1.0) 339 (113) ND ND = Not determined ND Day 87 38.3 (11.9) 1.8 (0.7) 471 (132) 383 (119) 23.9 (7.1) Based on a population pharmacokinetic analysis, average steady-state concentrations (C ss ) of norethindrone acetate and ethinyl estradiol for the norethindrone acetate and ethinyl estradiol 1/5 tablets are estimated to be 2.6 ng/mL and 11.4 pg/mL, respectively.

C ss values of norethindrone and ethinyl estradiol for the norethindrone acetate and ethinyl estradiol 0.5/2.5 tablets are estimated to be 1.1 ng/mL and 5.4 ng/mL, respectively. The pharmacokinetics of ethinyl estradiol and norethindrone acetate were not affected by age, (age range 40-62 years), in the postmenopausal population studied. Figure 1 Distribution The distribution of exogenous estrogens is similar to that of endogenous estrogens.

Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Estrogens circulate in the blood largely bound to SHBG and albumin. Volume of distribution of norethindrone and ethinyl estradiol ranges from 2 to 4 L/kg.

Plasma protein binding… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 16 words ▾

12.2Pharmacodynamics Currently, there are no pharmacodynamic data known for norethindrone acetate and ethinyl estradiol tablets.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Effects on Vasomotor Symptoms A 12-week placebo-controlled, multicenter, randomized clinical trial was conducted in 266 symptomatic women who had at least 56 moderate to severe hot flushes during the week prior to randomization. On average, patients had 12 hot flushes per day upon study entry. A total of 66 women were randomized to receive norethindrone acetate and ethinyl estradiol 1/5 and 66 women were randomized to the placebo group.

Norethindrone acetate and ethinyl estradiol 1/5 was shown to be statistically better than placebo at weeks 4, and 12 for relief of the frequency of moderate to severe vasomotor symptoms (see Table 3 ). In Table 4, norethindrone acetate and ethinyl estradiol 1/5 was shown to be statistically better than placebo at weeks 4 and 12 for relief of the severity of moderate to severe vasomotor symptoms. Table 3: Mean Change from Baseline in the Number of Moderate to Severe Vasomotor Symptoms per Week-ITT Population, LOCF Visit Placebo (N=66) Norethindrone Acetate and Ethinyl Estradiol 0.5/2.5 (N=67) Norethindrone Acetate and Ethinyl Estradiol 1/5 (N=66) ITT = intent to treat; LOCF = last observation carried forward; CI = confidence interval 2 randomized subjects (1 in Placebo and 1 in norethindrone acetate and ethinyl estradiol) did not return diaries.

Baseline The baseline number of moderate to severe vasomotor symptoms (MSVS) is the weekly average number of MSVS during the two week prerandomization observation period. Mean (SD) 76.5 (21.4) 77.6 (26.5) 70.0 (16.6) Week 4 Mean (SD) 39.4 (27.6) 30.2 (26.1) 20.4 (22.7) Mean Change from Baseline (SD) -37.0 (26.6) -47.4 Denotes statistical significance at the 0.05 level (26.1) -49.6 (22.1) p-Value vs. Placebo (95% CI) ANCOVA - Analysis of Covariance model where the observation variable is change from baseline; independent variables include treatment, center and baseline as covariate.

The 95% CI -Mann-Whitney confidence interval for the difference between means (not stratified by center). 0.041 ( -20.0, -1.0) <0.001 ( -22.0, -6.0) Week 12 Mean (SD) 31.1 (27.0) 13.8 (20.4) 11.3 (18.9) Mean Change from Baseline (SD) -45.3 (30.2) -63.8 (27.5) -58.7 (23.1) p-Value vs. Placebo (95% CI) <0.001 ( -27.0, -7.0) <0.001 ( -25.0, -5.0) Table 4: Mean Change from Baseline in the Daily Severity Score of Moderate to Severe Vasomotor Symptoms per Week - ITT Population, LOCF Visit Placebo (N=66) Norethindrone Acetate and Ethinyl Estradiol 0.5/2.5 (N=67) Norethindrone Acetate and Ethinyl Estradiol 1/5 (N=66) ITT = intent to treat; LOCF = last observation carried forward; CI = confidence interval 2 randomized subjects (1 in Placebo and 1 in norethindrone acetate and ethinyl estradiol) did not return diaries.

Baseline The baseline severity of moderate to severe vasomotor symptoms (MSVS) is the daily severity score of MSVS during the two week pre-randomization observation period. Mean (SD) 2.49 (0.26) 2.48 (0.22) 2.47 (0.23) Week 4 Mean (SD) 2.13 (0.74) 1.88 (0.89) 1.45 (1.03) Mean Change from Baseline (SD) -0.36 (0.68) -0.59 (0.83) -1.02 Denotes statistical significance at the 0.05 level (1.06) p-Value vs. Placebo (95% CI) ANCOVA - Analysis of Covariance model where the observation variable is change from baseline; independent variables include treatment, center and baseline as covariate.

The 95% CI - Mann-Whitney confidence interval for the difference between means (not stratified by center). - 0.130 ( -0.3, 0.0) <0.001 ( -0.9, -0.2) Week 5 Mean (SD) 2.06 (0.79) 1.68 (0.99) 1.23 (1.03) Mean Change from Baseline (SD) -0.44 (0.74) -0.80 (0.94) -1.24 (1.07) p-Value vs. Placebo (95% CI) - 0.041 ( -0.4, -0.0) <0.001 ( -1.2, -0.3) Week 12 Mean (SD) 1.82 (1.03) 1.22 (1.11) 1.02 (1.16) Mean Change from Baseline (SD) -0.67 (1.02) -1.26 (1.08) -1.45 (1.19) p-Value vs. Placebo (95% CI) - 0.002 ( -0.9, -0.2) <0.001 ( -1.4, -0.3)

14.2Effects on the Endometrium A 2-year, placebo-controlled, multicenter, randomized clinical trial was conducted to determine the safet… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 35 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 32 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.

📚 References 202 words ▾

15 REFERENCES Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause. JAMA.

2007;297:1465-1477. Hsia J, et al. Conjugated Equine Estrogens and Coronary Heart Disease.

Arch Int Med. 2006;166:357-365. Cushman M, et al.

Estrogen Plus Progestin and Risk of Venous Thrombosis. JAMA. 2004;292:1573-1580.

Curb JD, et al. Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus. Arch Int Med.

2006;166:772-780. Chlebowski RT, et al. Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women.

JAMA. 2003;289:3234-3253. Stefanick ML, et al.

Effects of Conjugated Equine Estrogens on Breast Cancer and Mammography Screening in Postmenopausal Women With Hysterectomy. JAMA. 2006;295:1647-1657.

Anderson GL, et al. Effects of Estrogen Plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures. JAMA.

2003;290:1739-1748. Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women.

JAMA. 2004;291:2947-2958. Jackson RD, et al.

Effects of Conjugated Equine Estrogen on Risk of Fractures and BMD in Postmenopausal Women With Hysterectomy: Results From the Women's Health Initiative Randomized Trial. J Bone Miner Res. 2006;21:817-828.

Hendrix SL, et al. Effects of Conjugated Equine Estrogen on Stroke in the Women's Health Initiative. Circulation.

2006;113:2425-2434.

📄 Patient Package Insert ~3 min read ▾

Patient Information Norethindrone Acetate and Ethinyl Estradiol Tablets USP 0.5 mg/2.5 mc g and 1 mg/5 mcg Read this Patient Information before you start taking norethindrone acetate and ethinyl estradiol tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment.

What is the most important information I should know about norethindrone acetate and ethinyl estradiol tablets (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). Using estrogens with progestins may increase your chances of getting a heart attack, strokes, breast cancer, or blood clots.

Using 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. Using estrogen-alone may increase your chance of getting cancer of the uterus (womb).

Using estrogen-alone may increase your chances of getting strokes or blood clots. Using 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 norethindrone acetate and ethinyl estradiol tablets .

What are norethindrone acetate and ethinyl estradiol tablets ? Norethindrone acetate and ethinyl estradiol tablets are a prescription medicine that contains two kinds of hormones, an estrogen and a progestin. What are norethindrone acetate and ethinyl estradiol tablets used for?

Norethindrone acetate and ethinyl estradiol tablets are used after menopause to: Reduce moderate to severe hot flushes Estrogens are hormones made by a woman's ovaries. The ovaries normally stop making estrogens when a woman is between 45 and 55 years old. This drop in body estrogen levels causes the "change of life" or menopause, the end of monthly menstrual periods.

Sometimes both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes "surgical menopause". When estrogen levels begin dropping, some women get very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense episodes of heat and sweating ("hot flashes" or "hot flushes").

In some women the symptoms are mild, and they will not need to take estrogens. In other women, symptoms can be more severe. Help reduce your chances of getting osteoporosis (thin weak bones) If you use norethindrone acetate and ethinyl estradiol tablets only to prevent osteoporosis from menopause, talk with your healthcare provider about whether a different treatment or medicine without estrogens might be better for you.

You and your healthcare provider should talk regularly about whether you still need treatment with norethindrone acetate and ethinyl estradiol tablets. Who should not take norethindrone acetate and ethinyl estradiol tablets ? Do not take norethindrone acetate and ethinyl estradiol tablets if you have had your uterus (womb) removed (hysterectomy).

Norethindrone acetate and ethinyl estradiol tablets contain a progestin to decrease the chance of getting cancer of the uterus. If you do not have a uterus, you do not need a progestin and you should not take norethindrone acetate and ethinyl estradiol tablets. Do not take norethindrone acetate and ethinyl estradiol tablets if you: have unusual vaginal bleeding Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb).

Your healthcare provider should check any unusual vaginal bleeding to find out the cause. currently have or have had certain cancers. Estrogens may increase the chance of getting certain types of cancers, including cancer of the breast or uterus. If you have or have had cancer,… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 7 words ▾

Warnings and Precautions, Malignant Neoplasms (5.2) 11/2017

📄 Package Label / Principal Display Panel 181 words ▾

PRINCIPAL DISPLAY PANEL - 1 mg/5 mcg Tablet Blister Pack Carton 3 Blister Cards of 28 Tablets each. NDC 75834-130-29 Norethindrone Acetate and Ethinyl Estradiol Tablets, USP 1 mg/5 mcg Each light yellow tablet contains norethindrone acetate 1 mg and ethinyl estradiol 5 mcg. Each tablet dispenser contains 28 white tablets This product (like all oral contraceptives) is intended to prevent pregnancy.

It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Rx Only NIVAGEN PHARMACEUTICALS PRINCIPAL DISPLAY PANEL - 1 mg/5 mcg Tablet Blister Pack Carton

PRINCIPAL DISPLAY PANEL - 0.5 mg/2.5 mcg Tablet Blister Pack Carton 3 Blister Cards of 28 Tablets each. NDC 75834-129-29 Norethindrone Acetate and Ethinyl Estradiol Tablets, USP 0.5 mg/2.5 mcg Each light yellow tablet contains norethindrone acetate 0.5 mg and ethinyl estradiol 2.5 mcg. Each tablet dispenser contains 28 light yellow tablets This product (like all oral contraceptives) is intended to prevent pregnancy.

It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Rx Only NIVAGEN PHARMACEUTICALS PRINCIPAL DISPLAY PANEL - 0.5 mg/2.5 mcg Tablet Blister Pack Carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

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Questions about this listing

What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 90 tablets (75834-0129-90). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Nivagen Pharmaceuticals, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 75834-0128-00 · Nivagen 75834-0130-29 · Nivagen →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.