Fyavolv Norethindrone Acetate and Ethinyl Estradiol .005 mg; 1 mg Tablet, Film Coated, 90-count — NDC 68180-828-09 (Billing 68180-0828-09)
This is a package of 90 tablets of Fyavolv Norethindrone Acetate and Ethinyl Estradiol .005 mg; 1 mg Tablet, Film Coated from Lupin Pharmaceuticals, Inc., marketed since Mar 2016 and currently FDA-listed; retail pharmacies pay about $0.5799 per tablet (NADAC).
NDC database record
One package, one record: these facts belong to NDC 68180-828-09 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 68180 labeler · 828 product · 09 package
- Package marketed since
- Mar 15, 2016
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Billing quantity
- 90 EA per package
- Barcode (UPC)
- 0368180828099, 0368180827092, 0368180827719, 0368180828716
- Medicaid fills, this package
- 182 prescriptions in the last four reported quarters
- FDA record last changed
- Sep 24, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 044337
- GCN: 92296
- GPI-14 (Medi-Span): 24993002250310
- HICL (First Databank): 001455
- AHFS class code: 68:16.04.00
- RxCUI (RxNorm): 1090992
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Estrogen class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
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 ↗Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Ask a licensed pharmacist directly — free, answered by our team.
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 system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.580 | $52.19 / 90 tablets |
| Medicaid paysCMS SDUD · 12 mo | $1.18 | $106.56 / 90 tablets |
| Medicare drug plans payPart D · Q2 2026 | $1.10 | $99.01 / 90 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 68180-0828-73 68180-828-73 Main listing | 3 POUCH in 1 CARTON / 1 BLISTER PACK in 1 POUCH / 28 TABLET, FILM COATED in 1 BLISTER PACK | $0.5799 / ea | $48.71 | 2020-11-30 | — | Active |
| 68180-0828-09 You're viewing this | 90 TABLET, FILM COATED in 1 BOTTLE | $0.5799 / ea | $52.19 | 2016-03-15 | — | Active |
This pack effectively ties for the lowest per-ea cost of the 2 priced pack sizes ($0.5799 NADAC).
This pack accounts for about 16% of this product's recent Medicaid fills; most go to a different pack size. See all packs ↓
Pack size FAQ
What quantity is in this package?
What NDC number is used to bill for this package of Fyavolv Norethindrone Acetate and Ethinyl Estradiol .005 mg; 1 mg Tablet, Film Coated?
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
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Jinteli 1 mg/1; 5 ug 00093-3122-42 | Teva | 140 tablets | $0.580 | AB | Availability likely | — |
| Fyavolv .005 mg/1; 1 mgthis 68180-0828-09 | Lupin | 90 tablets | $0.580 | AB | Availability likely | — |
| Norethindrone Acetate and Ethinyl Estradiol 1 mg/1; 5 ug 68462-0657-29 | Glenmark | 84 tablets | $0.580 | AB | Availability likely | — |
| Norethindrone Acetate and Ethinyl Estradiol 1 mg/1; .005 mg 75834-0130-29 | Nivagen | 84 tablets | $1.104 | AB | Discontinued | +90% |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
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?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 5, 2026
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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 776XM7047L
Calcium stearate is a white powder derived from stearic acid and calcium. It works as a lubricant and glidant to help the medicine flow smoothly during manufacturing and prevent ingredients from sticking to equipment.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII L06K8R7DQK
A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII B697894SGQ
Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII R0ZB2556P8
Tocopherol is a form of vitamin E derived from plant oils. It acts as an antioxidant in medicines to prevent oils and fats from breaking down and spoiling during storage.
9 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 5, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Lupin Pharmaceuticals, Inc. labeler code 68180
- Rufinamide 200 mg Tablet, Film Coated NDC 68180-803-06
- Rufinamide 400 mg Tablet, Film Coated NDC 68180-804-16
- Lanthanum Carbonate 500 mg Tablet, Chewable NDC 68180-819-42
- Lanthanum Carbonate 750 mg Tablet, Chewable NDC 68180-820-46
- Lanthanum Carbonate 1000 mg Tablet, Chewable NDC 68180-821-47
- Fyavolv Norethindrone Acetate and Ethinyl Estradiol .0025 mg; .5 mg Tablet, Film Coated NDC 68180-827-09
- TRI-LO-MARZIA norgestimate and ethinyl estradiol Kit NDC 68180-837-73
- Norgestimate and ethinyl estradiol Kit NDC 68180-838-73
- Norgestimate and Ethinyl Estradiol Kit NDC 68180-840-73
- Levonorgestrel and Ethinyl Estradiol Kit NDC 68180-843-13
- Kurvelo levonorgestrel and ethinyl estradiol Kit NDC 68180-844-73
- Daysee LEVONORGESTREL AND ETHINYL ESTRADIOL Kit NDC 68180-846-13
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER See full prescribing information for complete boxed warning. Estrogen Plus Progestin Therapy 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) ( 5.1 ) The WHI estrogen plus progestin substudy reported 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 ) Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia ( 5.1 , 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 ) 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 ) Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 ) 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 )] . Once 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 persisten… [Excerpted — this section continues on DailyMed.]
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Fyavolv is 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 ▾
2 DOSAGE AND ADMINISTRATION One tablet orally once daily ( 2.1 , 2.2 ) Use estrogen, alone or in combination with a progestogen, at the lowest effective dose and 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.
2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Take a single Fyavolv tablet, orally once daily.
2.2Prevention of Postmenopausal Osteoporosis Take a single Fyavolv tablet, orally once daily.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablet: 0.5 mg norethindrone acetate and 0.0025 mg ethinyl estradiol ( 3 ) Tablet: 1 mg norethindrone acetate and 0.005 mg ethinyl estradiol ( 3 ) The following two strengths of Fyavolv tablets are available: Fyavolv tablets, (0.5 mg/0.0025 mg): Each are white to off-white, round film-coated tablet, debossed with "F51" on one side and "LU" on the other side contains 0.5 mg norethindrone acetate and 0.0025 mg ethinyl estradiol. Fyavolv tablets, (1 mg/0.005 mg): Each are blue, round film-coated tablet, debossed with "F52" on one side and "LU" on the other side contains 1 mg norethindrone acetate and 0.005 mg ethinyl estradiol.
⛔ Contraindications ▾
4 CONTRAINDICATIONS 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 Fyavolv ( 4 ) Hepatic impairment or disease ( 4 , 5.10 ) Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 ) Fyavolv is 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 Fyavolv . Hepatic impairment or disease.
Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.
⚠️ Warnings and Cautions ▾
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 risks 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, respectively) [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 strokes per 10,000 women-years, respectively).
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 pl… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most common adverse reactions with Fyavolv (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 Lupin Pharmaceuticals, Inc. at 1-800-399-2561, or FDA at 1-800-FDA-1088 or www.fda.gov/Medwatch . 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 )] .
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 are shown in Table 1. Table 1.
Associated Adverse Reactions Reported by ≥5 Percent of Women by Body System* * 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 woman may have had more than one AE per body system BODY SYSTEM/ Adverse Reaction Number (Percent) of Subjects Placebo N = 247 Norethindrone Acetate and Ethinyl Estradiol 0.5/2.5 N = 244 Norethindrone Acetate and Ethinyl Estradiol 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. 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 cramps; back pain; changes in libido; urticaria, angioedema, anaphylactoid/anaph… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. ( 7.1 ) 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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Norethindrone acetate and ethinyl estradiol is not indicated for use in pregnancy. There are no data with the use of norethindrone acetate and ethinyl estradiol 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 breastfeeding 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 and any potential adverse effects on the breastfed child from norethindrone acetate and ethinyl estradiol or from the underlying maternal condition.
8.4Pediatric Use Norethindrone acetate and ethinyl estradiol is 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 to determine whether those over 65 years of age differ from younger subjects in their response to norethindrone acetate and ethinyl estradiol. 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 )] .
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Norethindrone acetate and ethinyl estradiol is not indicated for use in pregnancy. There are no data with the use of norethindrone acetate and ethinyl estradiol 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 ▾
8.4Pediatric Use Norethindrone acetate and ethinyl estradiol is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.
🧓 Geriatric Use ▾
8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing norethindrone acetate and ethinyl estradiol to determine whether those over 65 years of age differ from younger subjects in their response to norethindrone acetate and ethinyl estradiol. 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 ▾
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 Fyavolv therapy with institution of appropriate symptomatic care.
🧬 Clinical Pharmacology ▾
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 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 tablet 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 tablet was not characterized due to assay sensitivity limitations. However, the multiple-dose pharmacokinetics were studied at a dose of 1 mg norethindrone acetate and 0.01 mg ethinyl estradiol in 18 postmenopausal women. Mean plasma concentrations are shown below (Figure 1) and… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
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 ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Fyavolv 0.5 mg/0.0025 mg are white to off-white, round film-coated tablets, debossed with "F51" on one side and "LU" on the other side, containing 0.5 mg of norethindrone acetate and 0.0025 mg of ethinyl estradiol. Fyavolv 0.5 mg/0.0025 mg are available in bottle of 90 tablets (NDC 68180-827-09) and in a blister (NDC 68180-827-71) containing 28 tablets enclosed in a pouch, such 3 pouches are packed in a carton (NDC 68180-827-73). Fyavolv 1 mg/0.005 mg are blue, round film-coated tablets, debossed with "F52" on one side and "LU" on the other side, containing 1 mg of norethindrone acetate and 0.005 mg of ethinyl estradiol.
Fyavolv 1 mg/0.005 mg are available in bottle of 90 tablets (NDC 68180-828-09) and in a blister (NDC 68180-828-71) containing 28 tablets enclosed in a pouch, such 3 pouches are packed in a carton (NDC 68180-828-73).
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].
📦 Storage and Handling ▾
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].
📋 Description ▾
11 DESCRIPTION Fyavolv (norethindrone acetate and ethinyl estradiol tablets USP) is a continuous dosage regimen of a progestin-estrogen combination for oral administration. The following strength of Fyavolv tablets is available: Fyavolv (0.5 mg/0.0025 mg): Each white to off-white, round film-coated tablet, debossed with "F51" on one side and "LU" on the other side contains 0.5 mg norethindrone acetate and 0.0025 mg ethinyl estradiol. Fyavolv (1 mg/0.005 mg): Each blue, round film-coated tablet, debossed with "F52" on one side and "LU" on the other side contains 1 mg norethindrone acetate and 0.005 mg ethinyl estradiol.
Each tablet contains the following inactive ingredients: calcium stearate, corn starch, hypromellose, lactose monohydrate, microcrystalline cellulose, polyethylene glycol 400, titanium dioxide and vitamin E. Each tablet of 1 mg/0.005 mg also contains FD&C Blue No. 2 Aluminum Lake.
The structural formulas are as follows. Ethinyl Estradiol [19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17α)-] Molecular Weight: 296.40 Molecular Formula: C 20 H 24 O 2 Norethindrone Acetate [19-Norpregn-4-en-20-yn-3-one, 17-(acetyloxy)-, (17α)-] Molecular Weight: 340.46 Molecular Formula: C 22 H 28 O 3 Figure 1 Figure 2
💬 Information for Patients ▾
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 progestogen therapy such as headache, breast pain and tenderness, nausea and vomiting. Distributed by: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States Manufactured by: Lupin Limited Pithampur (M.P.) - 454 775 India Revised: November 2024 image
🍼 Nursing Mothers ▾
8.2Lactation Risk Summary Estrogens plus progestogens are present in human milk and can reduce milk production in breastfeeding 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 and any potential adverse effects on the breastfed child from norethindrone acetate and ethinyl estradiol or from the underlying maternal condition.
🧬 Pharmacokinetics ▾
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 tablet 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 tablet was not characterized due to assay sensitivity limitations. However, the multiple-dose pharmacokinetics were studied at a dose of 1 mg norethindrone acetate and 0.01 mg ethinyl estradiol 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 norethindrone acetate and 0.005 mg ethinyl estradiol and 1/10 are slightly more than proportional to dose when compared to 0.5 mg norethindrone acetate and 0.0025 mg ethinyl estradiol 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 norethindrone acetate and ethinyl estradiol 1/10 tablet.
Figure 1. Mean Steady-State (Day 87) Plasma Norethindrone and Ethinyl Estradiol Concentrations Following Continuous Oral Administration of 1 mg Norethindrone Acetate and 0.01 mg Ethinyl Estradiol Tablets Table 2. Mean (SD) Single-Dose (Day 1) and Steady-State (Day 87) Pharmacokinetic Parameters† Following Administration of 1 mg Norethindrone Acetate and 0.01 mg Ethinyl Estradiol Tablets † C max = Maximum plasma concentration; t max = time of C max ; AUC (0-24) = 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 C max t max AUC (0-24) CL/F t ½ 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 pg/mL hr pg·hr/mL mL/min hr Estradiol Day 1 33.5 (13.7) 2.2 (1.0) 339 (113) ND ‡ 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 (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 conce… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman's therapeutic response to norethindrone acetate and ethinyl estradiol 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 ▾
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 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 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 women (1 in Placebo and 1 in norethindrone acetate and ethinyl estradiol) did not return diaries. Visit Placebo (N = 66) Norethindrone Acetate and Ethinyl Estradiol 0.5/2.5 (N = 67) Norethindrone Acetate and Ethinyl Estradiol 1/5 (N = 66) Baseline [1] Mean (SD) 76.5 (21.4) 77.6 (26.5) 70.0 (16.6) Week 4 Mean (SD) Mean Change from Baseline (SD) p-Value vs. Placebo (95 percent CI) [2] 39.4 (27.6) -37.0 (26.6) 30.2 (26.1) -47.4 è (26.1) 0.041 (-20.0, -1.0) 20.4 (22.7) -49.6 è (22.1) <0.001 (-22.0,-6.0) Week 12 Mean (SD) Mean Change from Baseline (SD) 31.1 (27.0) -45.3 (30.2) 13.8 (20.4) -63.8 è (27.5) 11.3 (18.9) -58.7 è (23.1) p-Value vs.
Placebo (95 percent CI) [2] <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 ¥ 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 estradiol) did not return diaries. Visit Placebo (N = 66) Norethindrone Acetate and Ethinyl Estradiol 0.5/2.5 (N = 67) Norethindrone Acetate and Ethinyl Estradiol 1/5 (N = 66) Baseline [1] Mean (SD) 2.49 (0.26) 2.48 (0.22) 2.47 (0.23) Week 4 Mean (SD) Mean Change from Baseline (SD) p-Value vs.
Placebo (95 percent CI) [2] 2.13 (0.74) -0.36 (0.68) - 1.88 (0.89) -0.59 (0.83) 0.130 (-0.3, 0.0) 1.45 (1.03) -1.02 ¥ (1.06) <0.001 (-0.9, -0.2) Week 5 Mean (SD) Mean Change from Baseline (SD) p-Value vs. Placebo (95 percent CI) [2] 2.06 (0.79) -0.44 (0.74) 1.68 (0.99) -0.80 ¥ (0.94) 0.041 (-0.4, -0.0) 1.23 (1.03) -1.24 ¥ (1.07) <0.001 (-1.2, -0.3) Week 12 Mean (SD) Mean Change from Baseline (SD) p-Value vs. Placebo (95 percent CI) [2] 1.82 (1.03) -0.67 (1.02) - 1.22 (1.11) -1.26 ¥ (1.08) 0.002 (-0.9, -0.2) 1.02 (1.16) -1.45 ¥ (1.19) <0.001 (-1.4, -0.3)
14.2Effect… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
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.
📚 References ▾
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 ▾
Patient Information Fyavolv™ (FYE-uh-volv) (norethindrone acetate and ethinyl estradiol tablets USP) 0.5 mg/0.0025 mg and 1 mg/0.005 mg Read this Patient Information before you start using Fyavolv 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 Fyavolv (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 attacks, 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 Fyavolv will affect your chances of these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with Fyavolv.
What is Fyavolv? Fyavolv is a prescription medicine that contains two kinds of hormones, an estrogen and a progestogen. What is Fyavolv used for?
Fyavolv is 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 Fyavolv 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 Fyavolv.
Who should not use Fyavolv? Do not use Fyavolv if you have had your uterus (womb) removed (hysterectomy). Fyavolv contains a progestogen to decrease the chance of getting cancer of the uterus (womb).
If you do not have a uterus, you do not need a progestogen and you should not use Fyavolv. Do not start using Fyavolv if you: • have any 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. • have been diagnosed with a bleeding disorder. • currently have or have had certain cancers . Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus (womb). If you have or have had cancer, ta… [Excerpted — this section continues on DailyMed.]
📄 Recent Major Changes ▾
RECENT MAJOR CHANGES Boxed Warning 5/2023 Warnings and Precautions, Malignant Neoplasms ( 5.2 ) 11/2023
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Fyavolv™ (norethindrone and ethinyl estradiol tablets USP) 0.5 mg/0.0025 mg Rx Only NDC 68180-827-09 Bottle Label: 90 Tablets Fyavolv™ (norethindrone and ethinyl estradiol tablets USP) 1 mg/0.005 mg Rx Only NDC 68180-828-09 Bottle Label: 90 Tablets Fyavolv™ (norethindrone and ethinyl estradiol tablets USP) 0.5 mg/0.0025 mg Rx Only Blister and Pouch Label: 28 Tablets - NDC 68180-827-71 Carton Label: 3 Blister of 28 Tablets Each - NDC 68180-827-73 Fyavolv™ (norethindrone and ethinyl estradiol tablets USP) 1 mg/0.005 mg Rx Only Blister and Pouch Label: 28 Tablets - NDC 68180-828-71 Carton Label: 3 Blister of 28 Tablets Each - NDC 68180-828-73 Bottle Label - 0.5 mg/0.0025 mg Bottle Label - 1 mg/0.005 mg Blister Label: 28 Tablets - NDC 68180-827-71 Pouch Label: 28 Tablets - NDC 68180-827-71 Carton Label: 3 Blister of 28 Tablets Each - NDC 68180-827-73 Blister Label: 28 Tablets - NDC 68180-828-71 Pouch Label: 28 Tablets - NDC 68180-828-71 Carton Label: 3 Blister of 28 Tablets Each - NDC 68180-828-73