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Norethindrone Acetate and Ethinyl Estradiol .5 mg; 2.5 ug Tablet, 90-count — NDC 68462-656-90 (Billing 68462-0656-90)

by Glenmark Pharmaceuticals Inc., USA · 90 TABLET in 1 BOTTLE

This is a package of 90 tablets of Norethindrone Acetate and Ethinyl Estradiol .5 mg; 2.5 ug Tablet from Glenmark Pharmaceuticals Inc., USA, marketed since Apr 2015 and currently FDA-listed.

NDC 68462-0656-90
🏷️ FDA NDC (as labeled) 68462-656-90 billing pads the product segment with a zero
This package
Contains90-count Pack sizes2 compare ↓
Also priced by: Part D plans $1.84/unit — full pricing hub ↓
Product page 68462-0656-29 Also comes in: 84 tablets 68462-656-29
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Sep 24, 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

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68462-656-90
Product NDC 68462-656
11-digit billing NDC 68462065690
RxCUI 1090992, 1251323, 1251334, 1251336
UNII 9S44LIC7OJ, 423D2T571U
UPC 0368462657294, 0368462656297
Application # ANDA203038
SPL Set ID cf549b5a-2707-4020-9f94-dab1260e1664
Established class (EPC) Estrogen
Mechanism of action Estrogen Receptor Agonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2015-04-02
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 68462-656-90 — 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 → 68462-0656-90. 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

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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
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 $165.40 / 90 tablets
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
68462-0656-29 68462-656-29 Main listing 3 POUCH in 1 CARTON / 1 BLISTER PACK in 1 POUCH / 28 TABLET in 1 BLISTER PACK $0.9127 / ea $76.67 2015-04-02 — Active
68462-0656-90 You're viewing this 90 TABLET in 1 BOTTLE — — 2015-04-02 — Active

This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 90-count package — 90 tablet in 1 bottle.
How does this package differ from NDC 68462-0656-29?
Both are Norethindrone Acetate and Ethinyl Estradiol .5 mg; 2.5 ug Tablet — the drug itself is identical. This page's package is the 90-count one, while NDC 68462-0656-29 is the 84 tablets package.
What NDC number is used to bill for this package of Norethindrone Acetate and Ethinyl Estradiol .5 mg; 2.5 ug 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 —
Norethindrone Acetate and Ethinyl Estradiol .5 mg/1; .0025 mg 75834-0129-29 Nivagen 84 tablets $1.368 AB Discontinued —
Norethindrone Acetate and Ethinyl Estradiol .5 mg/1; 2.5 ugthis 68462-0656-90 Glenmark 90 tablets — AB FDA listed —
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

🏛️
2015
On the market since
Apr 2015
📍
2026
Currently FDA-listed
11 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.

What it looks like

Color Pink / White
ShapeRound
ImprintD6
Size6 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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

LabelerGlenmark Pharmaceuticals Inc., USA
Application holderGLENMARK PHARMACEUTICALS LTD
FDA applicationANDA203038 (ANDA)
Labeler code68462
First marketedApr 2015
Product typeHuman Prescription Drug
Portfolio343 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 📋 Description 💬 Information for Patients 🧬 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, 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 pulmonary embolism (PE), deep vein thrombosis (DVT), 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 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 )].

Breast Cancer The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions ( 5.2 ) and Clinical Studies ( 14.5 )]. Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known.

Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile. Prescribe estrogens with or without progestogens 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 progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, 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 The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg)-alone, relative to placebo [see Warnings and Precautions ( 5.1 ) and Clinical Studies ( 14.5 )]. The WHIMS estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, 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-alone therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions ( 5.1 , 5.3 ), and Clinical Studies ( 14.5 , 14.6 )]. Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI.

Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estro… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage 94 words ▾

1 INDICATIONS AND USAGE Norethindrone acetate and ethinyl estradiol tablets are a combination of an estrogen and 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, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis.

⏱️ Dosage and Administration 98 words ▾

2 DOSAGE AND ADMINISTRATION Use estrogen, alone or in combination with a progestogen, at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Re-evaluate postmenopausal women periodically as clinically appropriate to determine whether treatment is still necessary. • One tablet orally once daily ( 2.1 , 2.2 )

2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Take a single norethindrone acetate and ethinyl estradiol tablet, orally once daily.

2.2Prevention of Postmenopausal Osteoporosis Take a single norethindrone acetate and ethinyl estradiol tablet, orally once daily

💊 Dosage Forms and Strengths 147 words ▾

3 DOSAGE FORMS AND STRENGTHS The following two strengths of Norethindrone Acetate and Ethinyl Estradiol Tablets, USP are available: Norethindrone Acetate and Ethinyl Estradiol Tablets, USP (0.5 mg/2.5 mcg): Each light pink to pink, round, flat-faced beveled edge, uncoated tablet contains 0.5 mg norethindrone acetate, USP and 2.5 mcg ethinyl estradiol, USP; debossed with ‘D5’ on one side and plain on the other side. Norethindrone Acetate and Ethinyl Estradiol Tablets, USP (1 mg/5 mcg): Each white to off-white, round, flat-faced beveled edge, uncoated tablet contains 1 mg norethindrone acetate, USP and 5 mcg ethinyl estradiol, USP; debossed with ‘D6’ on one side and plain on the other side. • Round, light pink to light tablet contains 0.5 mg norethindrone acetate and 2.5 mcg ethinyl estradiol ( 3 ) • Round, white to off-white tablet contains 1 mg norethindrone acetate and 5 mcg ethinyl estradiol ( 3 )

⛔ Contraindications ~1 min read ▾

4 CONTRAINDICATIONS Norethindrone acetate and ethinyl estradiol tablets are contraindicated in women with any of the following conditions: • Undiagnosed abnormal genital bleeding [see Warnings and Precautions ( 5.2 )]. • Breast cancer or a history of breast cancer [see Warnings and Precautions ( 5.2 )]. • Estrogen-dependent neoplasia [see Warnings and Precautions ( 5.2 )]. • Active DVT, PE or a history of these conditions [see Warnings and Precautions ( 5.1 )]. • Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions [see Warnings and Precautions ( 5.1 )]. • Known anaphylactic reaction, angioedema, or hypersensitivity to norethindrone acetate and ethinyl estradiol tablets . • Hepatic impairment or disease. • Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. • Undiagnosed abnormal genital bleeding ( 4 , 5.2 ) • Breast cancer or a history of breast cancer ( 4 , 5.2 ) • 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, angioedema or hypersensitivity to norethindrone acetate and ethinyl estradiol tablets ( 4 ) • Hepatic impairment or disease ( 4 , 5.10 ) • Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )

⚠️ 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 Increased risk of PE, DVT, stroke, and MI are reported with estrogen plus progestin therapy. Increased risks of stroke and DVT are reported with estrogen-alone therapy. Immediately discontinue estrogen with or without progestogen therapy if any of these occur or are suspected.

Manage appropriately any 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). Stroke The WHI estrogen plus progestin substudy reported a statistically significant increased risk of stroke 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 strokes per 10,000 women- years) [ see Clinical Studies ( 14.5 ) ].

The increase in risk was demonstrated after the first year and persisted. 1 Immediately discontinue estrogen with or without progestogen therapy if a stroke occurs or is suspected. The WHI estrogen-alone substudy, reported a statistically significant increased risk of stroke 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 ) ] . Immediately discontinue estrogen-alone therapy if a stroke occurs or is suspected. 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 The WHI estrogen plus progestin substudy reported an increased risk (not statistically significant) of coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) in those 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 ) ] .

The WHI estrogen-alone substudy reported no overall effect on CHD events in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies ( 14.5 )] . Subgroup analyses of women 50 to 59 years of age, who were less than 10 years since menopause, suggest a reduction (not statistically significant) of CHD events in those women receiving CE (0.625 mg)-alone compared to placebo (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 the CE plus MPA group and the pl… [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 with norethindrone acetate and ethinyl estradiol tablets (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 Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 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 women 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 Women by Body System * BODY SYSTEM/ Adverse Reaction Number (Percent) of Subjects Placebo Norethindrone Acetate and Ethinyl Estradiol Tablets 0.5/2.5 Norethindrone Acetate and Ethinyl Estradiol Tablets 1/5 N = 247 N = 244 N = 258 BODY AS A WHOLE 23 (12.8) 30 (16.9) 30 (15.7) Edema - Generalized 10 (4) 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) 20 (7.8) *The total number of women for each body system may be less than the number of women with AEs in that body system because a women may have had more than one AE per body system

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 cramp… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 193 words ▾

7 DRUG INTERACTIONS 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 and progestin 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 and progestins, 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 the estrogen or the progestin or both and may result in adverse reactions. 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. 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.

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. (7.1)

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Norethindrone acetate and ethinyl estradiol tablets are not indicated for use in pregnancy. There are no data with the use of norethindrone acetate and ethinyl estradiol tablets in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined (estrogens and progestins) product before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

8.2Lactation Risk Summary Estrogens plus progestogens are present in human milk and can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for norethindrone acetate and ethinyl estradiol tablets and any potential adverse effects on the breastfed child from norethindrone acetate and ethinyl estradiol tablets or from the underlying maternal condition.

8.4Pediatric Use Norethindrone acetate and ethinyl estradiol tablets are not indicated for use in pediatric patients. 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 women8 [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.6 )] .

🤰 Pregnancy 99 words ▾

8.1Pregnancy Risk Summary Norethindrone acetate and ethinyl estradiol tablets are not indicated for use in pregnancy. There are no data with the use of norethindrone acetate and ethinyl estradiol tablets in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined (estrogens and progestins) product before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

🧒 Pediatric Use 27 words ▾

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

🧓 Geriatric Use ~1 min read ▾

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 women8 [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.6 )] .

🆘 Overdosage 45 words ▾

10 OVERDOSAGE Overdosage of estrogen plus progestogen 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 therapy with institution of appropriate symptomatic care.

🧬 Clinical Pharmacology ~2 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 Generally, a serum estrogen concentration does not predict an individual woman’s therapeutic response to norethindrone acetate and ethinyl estradiol tablets nor her risk for adverse outcomes. Likewise, exposure comparisons across different estrogen products to infer efficacy or safety for the individual woman may not be valid.

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 post-menopausal women. Mean plasma concentrations are shown below (Figure 1) and pharmacokinetic parameters… [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 213 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Norethindrone Acetate and Ethinyl Estradiol Tablets, USP are available in the following strengths and package sizes: Norethindrone Acetate and Ethinyl Estradiol Tablets, USP 0.5 mg/2.5 mcg, are light pink to pink, round, flat-faced, beveled edge, uncoated, tablets debossed with “D5” on one side and plain on the other side. Each tablet contains 0.5 mg norethindrone acetate, USP and 2.5 mcg ethinyl estradiol, USP and are available as: NDC 68462-656-90 Bottle of 90 Tablets NDC 68462-656-29 1 carton containing 3 individual foil pouches (68462-656-84).

Each pouch contains 1 blister of 28 tablets (68462-656-84) Norethindrone Acetate and Ethinyl Estradiol Tablets, USP 1 mg/5 mcg are white to off-white, round, flat-faced, beveled edge, uncoated tablets debossed with “D6” on one side plain on the other side. Each tablet contains 1 mg norethindrone acetate, USP and 5 mcg ethinyl estradiol, USP and are available as: NDC 68462-657-90 Bottle of 90 Tablets NDC 68462-657-29 1 carton containing 3 individual foil pouches (68462-657-84). Each pouch contains 1 blister of 28 tablets (68462-657-84).

16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Keep norethindrone acetate and ethinyl estradiol tablets out of the reach of children.

📋 Description 178 words ▾

11 DESCRIPTION Norethindrone Acetate and Ethinyl Estradiol Tablets, USP is a continuous dosage regimen of a progestin-estrogen combination for oral administration. The following two strengths of Norethindrone Acetate and Ethinyl Estradiol Tablets, USP are available as: Norethindrone Acetate and Ethinyl Estradiol Tablets USP (0.5 mg/2.5 mcg): Each light pink to pink, round, flat-faced beveled edge, uncoated tablet contains 0.5 mg norethindrone acetate, USP and 2.5 mcg ethinyl estradiol, USP. Norethindrone Acetate and Ethinyl Estradiol Tablets USP (1 mg/5 mcg): Each white to off-white, round, flat-faced beveled edge, uncoated tablet contains 1 mg norethindrone acetate, USP and 5 mcg ethinyl estradiol, USP.

Each tablet also contains the following inactive ingredients: calcium stearate, cornstarch, lactose monohydrate, microcrystalline cellulose, povidone and vitamin E and talc. The 0.5 mg/2.5 mcg light pink to pink tablet also contains D&C red no. 30.

The structural formulas are as follows Ethinyl Estradiol, USP [19-Nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol] Molecular Weight: 296.40 Molecular Formula: C 20 H 24 O 2 Norethindrone Acetate USP [19-Norpregn-4-en-20-yn-3-one, 17-(acetyloxy)-, (17 α)] Molecular Weight: 340.46 Molecular Formula: C 22 H 28 O 3 eestructure noreestructure

💬 Information for Patients 137 words ▾

17 PATIENT COUNSELING INFORMATION Advise women to read the FDA-approved patient labeling ( Patient Information ) Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see Warnings and Precautions ( 5.2 )] . Possible Serious Adverse Reactions with Estrogen Plus Progestogen Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen plus progestogen therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] .

Possible Common Adverse Reactions with Estrogen Plus Progestogen Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen plus progetogen therapy such as headache, breast pain and tenderness, nausea and vomiting. Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com May 2025 logo1

🧬 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 post-menopausal 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† Following Administration of 1 mg NA/10 mcg EE Tablets C max t max AUC (0 to 24) CL/F t 1/2 NORETHINDRONE ng/mL hr ng•hr/mL mL/min hr Day 1 6 (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) 339 (113) ND ‡ ND ‡ Day 87 38.3 (11.9) 1.8 (0.7) 471 (132) 383 (119) 23.9 (7.1) † C max = Maximum plasma concentration; t max = time of C max ; AUC (0 to 24) = Area under the plasma concentration-time curve over the dosing interval; and CL/F = Apparent oral clearance; t ½ = Elimination half-life ‡ ND = Not determined Based on a population pharmacokinetic analysis, average steady-state concentrations (Css) of norethindrone and ethinyl estradiol for norethindrone acetate and ethinyl estradiol 1/5 tablets are estimated to be 2.6 ng/mL and 11.4 pg/mL, respectively.

Css values of norethindrone and ethinyl estradiol for 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 to 62 years), in the postmenopausal population studied. 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 of b… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 48 words ▾

12.2Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman’s therapeutic response to norethindrone acetate and ethinyl estradiol tablets nor her risk for adverse outcomes. Likewise, exposure comparisons across different estrogen products to infer efficacy or safety for the individual woman may not be valid.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Effects on Vasomotor Symptoms in Postmenopausal Women 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, women had 12 hot flushes per day upon study entry. A total of 66 women were randomized to receive norethindrone acetate and ethinyl estradiol tablets 1/5 and 66 women were randomized to the placebo group.

Norethindrone acetate and ethinyl estradiol tablets 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 tablets 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 Tablets 0.5 /2.5 (N = 67) Norethindrone Acetate and Ethinyl Estradiol Tablets 1 /5 (N = 66) Baseline [1] Mean (SD) 76.5 (21.4) 77.6 (26.5) 70 (16.6) Week 4 Mean (SD) 39.4 (27.6) 30.2 (26.1) 20.4 (22.7) Mean Change From Baseline (SD) -37 (26.6) -47.4 è (26.1) -49.6 è (22.1) p-Value vs. Placebo (95 percent CI) [2] 0.041 (-20, -1) <0.001 (-22, -6) Week 12 Mean (SD) 31.1 (27) 13.8 (20.4) 11.3 (18.9) Mean Change from Baseline (SD) -45.3 (30.2) -63.8 è (27.5) -58.7 è (23.1) p-Value vs.

Placebo (95 percent CI) [2] <0.001 (-27, -7) <0.001 (-25, -5) è Denotes statistical significance at the 0.05 level [1] The baseline number of moderate to severe vasomotor symptoms (MSVS) is the weekly average number of MSVS during the two week pre-randomization observation period. [2] ANCOVA -Analysis of Covariance model where the observation variable is change from baseline; independent variables include treatment, center and baseline as covariate. The 95 percent CI -Mann-Whitney confidence interval for the difference between means (not stratified by center).

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 tablets) did not return diaries. 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 Tablets 0.5 /2.5 (N = 67) Norethindrone Acetate and Ethinyl Estradiol Tablets 1 /5 (N = 66) Baseline [1] 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 ¥ (1.06) p-Value vs Placebo (95 percent CI) [2] - 0.130 (-0.3, 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) -0.8 ¥ (0.94) -1.24 ¥ (1.07) p-Value vs Placebo (95 percent CI) [2] - 0.041 (-0.4, -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 percent CI) [2] - 0.002 (-0.9, -0.2) <0.001 (-1.4, -0.3) ¥ Denotes statistical significance at the 0.05 level [1] 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. [2] ANCOVA - Analysis of Covariance model where the observation variable is change from baseline; independent variables include treatment, center and baseline as covariate.

The 95 percent CI - Mann-Whitney confidence interval for the difference between means (not stratified by center). ITT = intent to treat; LOCF = last observation carried forward; CI = confidence interval 2 randomized women (1 in Placebo and 1 in norethindrone acetate and ethinyl… [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 218 words ▾

15 REFERENCES 1. Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause.

JAMA . 2007;297:1465-1477. 2.

Hsia J, et al. Conjugated Equine Estrogens and Coronary Heart Disease. Arch Int Med.

2006;166:357-365. 3. Cushman M, et al.

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

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

Arch Int Med . 2006;166:772-780. 5.

Chlebowski RT, et al. Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women. JAMA .

2003;289:3234-3253. 6. 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.

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

JAMA. 2003;290:1739-1748. 8.

Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women. JAMA.

2004;291:2947-2958. 9. 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.

10. 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 (nor-eth-IN-drone ASS-uh-TATE and ETH in il es tra DYE ole) Tablets, USP 0.5 mg/2.5 mcg and 1 mg/5 mcg Read this Patient Information before you start using 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 progestogen)? • Do not use estrogens with or without progestogens to prevent heart disease, heart attacks, strokes or dementia (decline of brain function). • Using estrogens with progestogens may increase your chances of getting heart attack, strokes, breast cancer, or blood clots. • Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women 65 years of age and older. • Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). • Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia (decline of brain function). • 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 and older. • Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia.

Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia. Because other products and doses have not been studied in the same way, it is not known how the use of norethindrone acetate and ethinyl estradiol tablets will affect your chances of these conditions. 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 progestogen. 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 use norethindrone acetate and ethinyl estradiol tablets? Do not use norethindrone acetate and ethinyl estradiol tablets if you have had your uterus (womb) removed (hysterectomy). Norethindrone acetate and ethinyl estradiol tablets contain a progestogen to decrease the chance of gettin… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 12 words ▾

Boxed Warning 5/2023 Warnings and Precautions, Malignant Neoplasms ( 5.2 ) 11/2023

📄 Package Label / Principal Display Panel 8 words ▾

PRINCIPAL DISPLAY PANEL carton-1mg-5mcg

PRINCIPAL DISPLAY PANEL carton-0-5mg-2-5mcg

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

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
84 tablets68462-0656-29 2,336 Rx · $112,220
90 tablets this page68462-0656-90 No Medicaid data
Drug total (last 4 qtrs): 2,336 Rx · 89,033 units · $112,220 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

About this NDC listing & data coverage

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Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
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.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Glenmark Pharmaceuticals Inc., USA. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 84 tablets (68462-0656-29). 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?
Glenmark Pharmaceuticals Inc., USA 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.
← 68462-0653-01 · GLENMARK 68462-0657-29 · Glenmark →
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.