HomeNDC LookupIngredientsEstradiol Valerate › 70700-0275-22
Estradiol valerate 40 mg/mL Injection, 5 mL — NDC 70700-0275-22 package photo

Estradiol valerate 40 mg/mL Injection, 5 mL

by Xiromed, LLC · 5 mL in 1 VIAL, MULTI-DOSE (70700-275-22)
NDC 70700-0275-22
🏷️ FDA NDC (as labeled) 70700-275-22 billing pads the product segment with a zero
Rx only Generic On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 70700-275-22
Product NDC 70700-275
11-digit billing NDC 70700027522
NCPDP billing unit ML — per mL (volume)
RxCUI 310189, 310190, 310191
UNII OKG364O896
Application # ANDA216656
SPL Set ID 2e5c7559-7420-168d-6272-92bb4d20035d
Established class (EPC) Estrogen
Mechanism of action Estrogen Receptor Agonists
Chemical class Estradiol Congeners
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2023-05-01
Route INTRAMUSCULAR
Dosage form INJECTION
Substance ESTRADIOL VALERATE
GPI-14 24000035201715
GCN Seq No 003200
GCN 10694
HICL code 001420
Ingredient (HICL) Estradiol Valerate
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 ESTRADIOL VALERATE 200 MG/5 ML
FDB brand name Estradiol Valerate
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AO · RLD · RS
Why two NDCs? The FDA registers this code as 70700-275-22 — 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 → 70700-0275-22. 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 Radioactive Diagnostic Agent class.

Pharmacologic class Radioactive Diagnostic Agent, Estrogen
Drug family (ATC) Natural and semisynthetic estrogens, plain, Progestogens and estrogens, sequential preparations
How it works Positron Emitting Activity, 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.

🏭 Manufacturer & labeler

LabelerXiromed, LLC
Application holderXIROMED PHARMA ESPANA SL
FDA applicationANDA216656 (ANDA)
Labeler code70700
First marketedMay 2023
Product typeHuman Prescription Drug
Portfolio42 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.

🩺 Clinical

Label name ESTRADIOL VALERATE 200 MG/5 ML Ingredient Estradiol Valerate
📗 Our plain-language guide HelloPharmacist
  • Estradiol is a form of estrogen — the main hormone your ovaries produce. It's most commonly prescribed to relieve moderate to severe menopausal symptoms like hot flashes and vagina...
  • Apply your patch to clean, dry skin — typically on your lower abdomen. Don't put it on your breasts or the same spot two patches in a row. Climara and Menostar are changed once a w...
  • Yes, and it's important to be aware of them. Estradiol — especially when combined with a progestogen — can raise the risk of blood clots, stroke, and breast cancer. Women with a ut...
  • Are there serious risks I need to know about?
📖 Read our full Estradiol guide →
5
Nutrient depletion considerations

Estradiol may be associated with lower levels of 5 nutrients — worth a chat with your pharmacist, not a cause for alarm.

An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
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.

🧪 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.

  • UNII LKG8494WBH
    Benzyl alcohol is a clear liquid used as a preservative and solvent in medicines. It helps prevent bacterial and fungal growth and dissolves other ingredients to create uniform liquid formulations.
  • UNII N863NB338G
    Benzyl benzoate is a liquid organic compound used as a solvent and preservative in medicines. It helps dissolve active ingredients and can extend shelf life by preventing microbial growth in liquid formulations.
  • UNII D5340Y2I9G
    Castor oil is a natural plant-based oil used in medicines as a lubricant, laxative agent, and solvent. It helps medicine ingredients dissolve or flow smoothly and can aid bowel movement in formulations designed for that purpose.

3 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient 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.

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.

💲 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 mLPer package
Retail pharmacies payNADAC · weekly $35.060 $175.30 / 5 ml
Medicaid paysCMS SDUD · 12 mo $42.30 $211.50 / 5 ml
Medicare drug plans payPart D · Q2 2026 $22.81 $114.06 / 5 ml
Medicare Part B allowsASP · J1380 $7.702 / J1380 unit
NADAC price history (per mL) — tap or hover for the price & month
Nov 2023 Jan 2026 Apr 2026 Aug 2026 $36.206 $31.971
▼ Down 1% over the last 11 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🧾 Billing & reimbursement

FDA NDC (as labeled)70700-275-22
11-digit billing NDC70700-0275-22
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ1380
DescriptorInjection, estradiol valerate, up to 10 mg
Billing units / pkg20 units
Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Estradiol Valerate 40 mg/mL 00143-9291-01 Hikma 1 vial $35.060 AO Availability likely
Estradiol Valerate 40 mg/mL 00517-0440-01 American 1 vial $35.060 AO Availability likely
Estradiol valerate 40 mg/mLthis 70700-0275-22 Xiromed, 5 ml $35.060 AO Availability likely
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

🏛️
2023
On the market since
May 2023
📍
2026
Currently FDA-listed
3 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.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 70700-0275-22, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
10.3K
Units reimbursed last 4 qtrs
36.2K
Gross reimbursed last 4 qtrs
$1.53M
Avg / prescription
$149.04
Avg / unit
$42.2997
Latest quarter Q4 2025
2.3KRx
Medicaid pays / mL
$42.2997
gross reimbursed
vs
NADAC / mL
$35.0598
acquisition cost
=
Spread
+$7.2399
+21% vs cost
What Medicaid paid per mL (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care
43% FFS 57% MCO
Fee-for-service · 4,400 Rx Managed care · 5,875 Rx
State Medicaid map
Alaska: no data reported AK Maine: 155 units · 11.1 per 100k residents ME Washington: 2,310 units · 29.6 per 100k residents WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 594 units · 10.4 per 100k residents MN Wisconsin: 135 units · 2.3 per 100k residents WI Michigan: 725 units · 7.2 per 100k residents MI New York: 5,905 units · 30.2 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 2,269 units · 53.6 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: 1,580 units · 12.6 per 100k residents IL Indiana: 595 units · 8.7 per 100k residents IN Ohio: 871 units · 7.4 per 100k residents OH Pennsylvania: 4,976 units · 38.4 per 100k residents PA New Jersey: 730 units · 7.9 per 100k residents NJ Massachusetts: 942 units · 13.5 per 100k residents MA California: 6,545 units · 16.8 per 100k residents CA Utah: no data reported UT Colorado: 650 units · 11.1 per 100k residents CO Nebraska: 235 units · 11.9 per 100k residents NE Missouri: no data reported MO Kentucky: 465 units · 10.3 per 100k residents KY West Virginia: no data reported WV Virginia: 1,010 units · 11.6 per 100k residents VA Maryland: 65 units · 1.1 per 100k residents MD Connecticut: 1,105 units · 30.6 per 100k residents CT Rhode Island: 770 units · 70.3 per 100k residents RI Arizona: 240 units · 3.2 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 2,475 units · 22.8 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: 735 units · 16.1 per 100k residents LA Mississippi: no data reported MS Alabama: 121 units · 2.4 per 100k residents AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.170.3
gray = no data reported
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Rhode Island 70.3 /100k
2 Oregon 53.6 /100k
3 Pennsylvania 38.4 /100k
4 Connecticut 30.6 /100k
5 New York 30.2 /100k
6 Washington 29.6 /100k
7 North Carolina 22.8 /100k
8 California 16.8 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Estradiol Valerate — the program that covers self-administered drugs. 4 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Estradiol Valerate. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$593.3K
Claims incl. refills
4.6K
Beneficiaries
3.1K
Spend / beneficiary
$192.96
Spend / claim
$128.68
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
70700-0275-22 You're viewing this 5 mL in 1 VIAL, MULTI-DOSE (70700-275-22) 2023-05-01 Active

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning ~2 min read

ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of “natural” estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses.

(See WARNINGS, Malignant neoplasms, Endometrial cancer ). CARDIOVASCULAR AND OTHER RISKS Estrogens and progestins should not be used for the prevention of cardiovascular disease. (See WARNINGS, Cardiovascular disorders ).

The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. (See CLINICAL PHARMACOLOGY, Clinical Studies ). The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo.

It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy. (See CLINICAL PHARMACOLOGY, Clinical Studies ). Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar.

Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT ESTRADIOL VALERATE INJECTION, USP (AN ESTROGEN HORMONE)? Estrogens increase the chances of getting cancer of the uterus. Report any unusual vaginal bleeding right away while you are taking estrogens.

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. Do not use estrogens with or without progestins to prevent heart disease, heart attacks, or strokes.

Using estrogens with or without progestins may increase your chances of getting heart attacks, strokes, breast cancer, and blood clots. Using estrogens with progestins may increase your risk of dementia. You and your healthcare provider should talk regularly about whether you still need treatment with Estradiol valerate injection, USP .

🎯 Indications and Usage 78 words

INDICATIONS AND USAGE Estradiol valerate injection, USP is indicated in the: Treatment of moderate to severe vasomotor symptoms associated with the menopause. Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.

Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. Treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only).

⏱️ Dosage and Administration ~2 min read

DOSAGE AND ADMINISTRATION When estrogen is prescribed for a postmenopausal woman with a uterus, progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.

Patients should be reevaluated periodically as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary (See BOXED WARNINGS and WARNINGS ). For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding. Care should be taken to inject deeply into the upper, outer quadrant of the gluteal muscle following the usual precautions for intramuscular administration.

By virtue of the low viscosity of the vehicles, the various preparations of Estradiol valerate injection, USP may be administered with a small gauge needle (i.e., 20 Gauge × 1 ½ inches long). Since the 40 mg potency provides a high concentration in a small volume, particular care should be observed to administer the full dose. Estradiol valerate injection, USP should be visually inspected for particulate matter and color prior to administration; the solution is clear, colorless to pale yellow.

Storage at low temperatures may result in the separation of some crystalline material which redissolves readily on warming. Note: A dry needle and syringe should be used. Use of a wet needle or syringe may cause the solution to become cloudy; however, this does not affect the potency of the material.

Patients should be started at the lowest dose for the indication. The lowest effective dose of Estradiol valerate injection, USP has not been determined for any indication. Treated patients with an intact uterus should be monitored closely for signs of endometrial cancer, and appropriate diagnostic measures should be taken to rule out malignancy in the event of persistent or recurring abnormal vaginal bleeding.

See PRECAUTIONS concerning addition of a progestin. For treatment of moderate to severe vasomotor symptoms, vulvar and vaginal atrophy associated with the menopause, the lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible. The usual dosage is 10 to 20 mg Estradiol valerate injection, USP every four weeks.

Attempts to discontinue or taper medication should be made at 3-month to 6-month intervals. For treatment of female hypoestrogenism due to hypogonadism, castration, or primary ovarian failure. The usual dosage is 10 to 20 mg Estradiol valerate injection, USP every four weeks.

For treatment of advanced androgen-dependent carcinoma of the prostate, for palliation only. The usual dosage is 30 mg or more administered every one or two weeks.

Contraindications 130 words

CONTRAINDICATIONS Estradiol valerate injection, USP should not be used in women with any of the following conditions: Undiagnosed abnormal genital bleeding. Known, suspected, or history of cancer of the breast. Known or suspected estrogen-dependent neoplasia.

Active deep vein thrombosis, pulmonary embolism or a history of these conditions. Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction). Liver dysfunction or disease.

Estradiol valerate injection, USP should not be used in patients with known hypersensitivity to its ingredients. Known or suspected pregnancy. There is no indication for Estradiol valerate injection, USP in pregnancy.

There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins from oral contraceptives inadvertently during early pregnancy. (See PRECAUTIONS ).

⚠️ Warnings ~3 min read

WARNINGS See BOXED WARNINGS. The use of unopposed estrogens in women who have a uterus is associated with an increased risk of endometrial cancer. 1.

Cardiovascular disorders Estrogen and estrogen/progestin therapy has been associated with an increased risk of cardiovascular events such as myocardial infarction and stroke, as well as venous thrombosis and pulmonary embolism (venous thromboembolism or VTE). Should any of these occur or be suspected, estrogens should be discontinued immediately. Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. a.

Coronary heart disease and stroke In the Women's Health Initiative (WHI) study, an increase in the number of myocardial infarctions and strokes has been observed in women receiving CE compared to placebo. These observations are preliminary. (See CLINICAL PHARMACOLOGY, Clinical Studies ).

In the CE/MPA substudy of WHI, an increased risk of coronary heart disease (CHD) events (defined as non-fatal myocardial infarction and CHD death) was observed in women receiving CE/MPA compared to women receiving placebo (37 vs. 30 per 10,000 women-years). The increase in risk was observed in year one and persisted.

In the same substudy of WHI, an increased risk of stroke was observed in women receiving CE/MPA compared to women receiving placebo (29 vs. 21 per 10,000 women-years). The increase in risk was observed after the first year and persisted.

In postmenopausal women with documented heart disease (n=2,763, average age 66.7 years) a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS) treatment with CE/MPA (0.625mg/2.5mg per day) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE/MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE/MPA-treated group than in the placebo group in year 1, but not during the subsequent years.

Two thousand three hundred and twenty one 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/MPA group and the placebo group in HERS, HERS II, and overall.

Large doses of estrogen (5 mg conjugated estrogens per day), comparable to those used to treat cancer of the prostate and breast, have been shown in a large prospective clinical trial in men to increase the risks of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis. b. Venous thromboembolism (VTE) In the Women's Health Initiative (WHI) study, an increase in VTE has been observed in women receiving CE compared to placebo. These observations are preliminary.

(See CLINICAL PHARMACOLOGY, Clinical Studies .) In the CE/MPA substudy of WHI, a 2-fold greater rate of VTE, including deep venous thrombosis and pulmonary embolism, was observed in women receiving CE/MPA compared to women receiving placebo. The rate of VTE was 34 per 10,000 women-years in the CE/MPA group compared to 16 per 10,000 women-years in the placebo group. The increase in VTE risk was observed during the first year and persisted.

If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. 2. Malignant neoplasms a.

Endometrial cancer The use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-fold greater than i…

🤒 Adverse Reactions ~1 min read

ADVERSE REACTIONS See BOXED WARNINGS, WARNINGS , and PRECAUTIONS . 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. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

The following additional adverse reactions have been reported with estrogen and/or progestin therapy. Genitourinary system Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, 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. Breasts Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.

Cardiovascular Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure. Gastrointestinal Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis, enlargement of hepatic hemangiomas. Skin Chloasma or melasma, which may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash.

Eyes Retinal vascular thrombosis; intolerance to contact lenses. Central Nervous System Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia. Miscellaneous Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.

For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact Xiromed, LLC at 844-XIROMED (844-947-6633) or visit www. Xiromed.com or www.fda.gov/medwatch.

🔄 Drug Interactions 92 words

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 drug metabolism. Inducers of CYP3A4 such as St.

John's Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.

🔄 Drug / Laboratory Test Interactions 193 words

D. Drug/Laboratory Test Interactions Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T 4 levels (by column or by radioimmunoassay) or T 3 levels by radioimmunoassay.

T 3 resin uptake is decreased, reflecting the elevated TBG. Free T 4 and free T 3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.

Other binding proteins may be elevated in serum (i.e., corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG)) leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).

Increased plasma HDL and HDL 2 cholesterol subfraction concentrations, reduced LDL cholesterol concentrations, increased triglycerides levels. Impaired glucose tolerance. Reduced response to metyrapone test.

🤰 Pregnancy 15 words

F. Pregnancy Estradiol valerate injection, USP should not be used during pregnancy. (See CONTRAINDICATIONS ).

🧒 Pediatric Use 51 words

H. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Large and repeated doses of estrogen over an extended period of time may accelerate epiphyseal closure. Therefore, periodic monitoring of bone maturation and effects on epiphyseal centers is recommended in patients in whom bone growth is not complete.

🧓 Geriatric Use 157 words

I. Geriatric Use Clinical studies of estradiol valerate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In the Women's Health Initiative Memory Study, including 4,532 women 65 years of age and older, followed for an average of 4 years, 82% (n = 3,729) were 65 to 74 while 18% (n = 803) were 75 and over.

Most women (80%) had no prior hormone therapy use. Women treated with conjugated estrogens plus medroxyprogesterone acetate were reported to have a two-fold increase in the risk of developing probable dementia. Alzheimer's disease was the most common classification of probable dementia in both the conjugated estrogens plus medroxyprogesterone acetate group and the placebo group.

Ninety percent of the cases of probable dementia occurred in the 54% of the women that were older than 70. (See WARNINGS, Dementia ). It is unknown whether these findings apply to estrogen alone therapy.

🆘 Overdosage 36 words

OVERDOSAGE Serious ill effects have not been reported following acute ingestion of large doses of estrogen-containing drug products by young children. Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females.

🧬 Clinical Pharmacology ~3 min read

CLINICAL PHARMACOLOGY 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, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. 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 follicle stimulating hormone (FSH), through a negative feedback mechanism.

Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. Pharmacokinetics Absorption Estrogens used in therapy are well absorbed through the skin, mucous membranes, and gastrointestinal tract. When applied for a local action, absorption is usually sufficient to cause systemic effects.

When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks. 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 sex hormone binding globulin (SHBG) and albumin. Metabolism Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions.

These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption.

In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. When given orally, naturally-occurring estrogens and their esters are extensively metabolized (first pass effect) and circulate primarily as estrone sulfate, with smaller amounts of other conjugated and unconjugated estrogenic species. This results in limited oral potency.

By contrast, synthetic estrogens, such as ethinyl estradiol and the nonsteroidal estrogens, are degraded very slowly in the liver and other tissues, which results in their high intrinsic potency. Estrogen drug products administered by non-oral routes are not subject to first-pass metabolism, but also undergo significant hepatic uptake, metabolism, and enterohepatic recycling. Excretion Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

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 drug metabolism. Inducers of CYP3A4 such as St.

John's Wort prepa…

📦 How Supplied / Storage and Handling 49 words

HOW SUPPLIED Estradiol valerate injection, USP Multiple Dose Vials 10 mg/mL (5 mL): NDC 70700-273-22 20 mg/mL (5 mL): NDC 70700-274-22 40 mg/mL (5 mL): NDC 70700-275-22 STORAGE Store between 20° to 25°C (68° to 77°F). (See USP Controlled Room Temperature.) Keep out of reach of children. Revised: 01/2026

📦 Storage and Handling 22 words

STORAGE Store between 20° to 25°C (68° to 77°F). (See USP Controlled Room Temperature.) Keep out of reach of children. Revised: 01/2026

📋 Description 111 words

DESCRIPTION Estradiol valerate injection, USP contains estradiol valerate, a long-acting estrogen in sterile oil solutions for intramuscular use. These solutions are clear, colorless to pale yellow. Formulations (per mL): 10 mg estradiol valerate in a vehicle containing 5 mg chlorobutanol (chloral derivative/preservative) and 905 mg sesame oil; 20 mg estradiol valerate in a vehicle containing 224 mg benzyl benzoate, 20 mg benzyl alcohol (preservative), and 733 mg castor oil; 40 mg estradiol valerate in a vehicle containing 447 mg benzyl benzoate, 20 mg benzyl alcohol, and 525 mg castor oil.

Estradiol valerate is designated chemically as estra-1,3,5(10)-triene-3, 17-diol(17β)-, 17-pentanoate. Graphic formula: C 23 H 32 O 3 MW 356.50 Chemical Structure

💬 Information for Patients 23 words

B. Patient Information Physicians are advised to discuss the PATIENT INFORMATION leaflet with patients for whom they prescribe Estradiol valerate injection, USP .

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