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Angeliq drospirenone and estradiol .5 mg; .25 mg Tablet, Film Coated, 14-count — NDC 50419-0482-72 package photo

Angeliq drospirenone and estradiol .5 mg; .25 mg Tablet, Film Coated, 14-count

by Bayer HealthCare Pharmaceuticals Inc. · 1 BLISTER PACK in 1 CARTON (50419-482-72) / 14 TABLET, FILM COATED in 1 BLISTER PACK (50419-482-71)
NDC 50419-0482-72
🏷️ FDA NDC (as labeled) 50419-482-72 billing pads the product segment with a zero
This package
Contains14-count Pack sizes2 compare ↓
Also priced by: Part D plans $6.35/unit — full pricing hub ↓
Also comes in: 28 tablets 50419-0482-03
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

🆔 Identity & classification

FDA NDC (as labeled) 50419-482-72
Product NDC 50419-482
11-digit billing NDC 50419048272
RxCUI 1483549, 1483550, 1483551, 1483552, 1483553, 1483554
UNII N295J34A25, 4TI98Z838E
Application # NDA021355
SPL Set ID 761834c2-6b61-4583-84c2-f1ca4a97c4f2
Established class (EPC) Progestin; Estrogen
Mechanism of action Estrogen Receptor Agonists
Chemical class Progesterone Congeners; Estradiol Congeners
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2012-02-29
Route ORAL
Dosage form TABLET, FILM COATED
Substance ESTRADIOL; DROSPIRENONE
GPI-14 24993002400310
GPI class Angeliq
GCN Seq No 069389
GCN 32417
HICL code 039160
Ingredient (HICL) Drospirenone/Estradiol
HIC1 code G
Therapeutic class — broad (HIC1) Female Genital System
HIC2 code G1
Therapeutic class — intermediate (HIC2) Estrogens
HIC3 code G1D
Therapeutic class — specific (HIC3) Estrogen-Progestin With Antimineralocorticoid Comb
AHFS code 68:16.04.00
AHFS class Estrogens
FDB label name ANGELIQ 0.25 MG-0.5 MG TABLET
FDB brand name Angeliq
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 50419-482-72 — 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 → 50419-0482-72. 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 Progestin class.

Pharmacologic class Progestin
Drug family (ATC) Progestogens
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

LabelerBayer HealthCare Pharmaceuticals Inc.
Application holderBAYER HEALTHCARE PHARMACEUTICALS INC
FDA applicationNDA021355 (NDA)
Labeler code50419
First marketedFeb 2012
Product typeHuman Prescription Drug
Portfolio62 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 ANGELIQ 0.25 MG-0.5 MG TABLET Ingredient Drospirenone/Estradiol

Supplement & herbal interactions

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

💊 What it looks like

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

🧪 Inactive Ingredients / Excipients

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

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII EX438O2MRT
    Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
  • 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.
  • 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.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII 30IQX730WE
    Polyethylene glycol 6000 is a synthetic polymer made from ethylene glycol units. It acts as a binder, filler, and solubilizer in medicines to help hold ingredients together, add bulk, and improve how well active drugs dissolve and absorb.
  • UNII K0KQV10C35
    Povidone K25 is a synthetic polymer made from vinyl pyrrolidone. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach for better absorption.
  • 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.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • 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.

9 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 DailyMed — 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.

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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $6.35 $88.91 / 14 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Angeliq .5 mg/1; .25 mgthis 50419-0482-72 Bayer 14 tablets — AB FDA listed —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
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

🏛️
2005
First FDA approval
Sep 2005
📍
2026
Currently FDA-listed
21 years listed
🛡️
2031
Latest patent/protection listed
not a guaranteed launch date
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Oct 2031. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Sep 28, 2005 AB TE-rated RLD RS ⏳ ~5.1 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 8906890 — drug product
2005 2007 2009 2011 2013 2015 2017 2019 2021 2023 2025 2027 2029 2031
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (1)
PatentTypeUse codeExpires
US 8906890 ↗ Drug product — Oct 22, 2031
Common questions
Is there a generic version of ANGELIQ 0.25 MG-0.5 MG TABLET?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for ANGELIQ 0.25 MG-0.5 MG TABLET. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
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 by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
28 tablets50419-0482-03 301 Rx · $86,850
14 tablets this page50419-0482-72 No Medicaid data
Drug total (last 4 qtrs): 301 Rx · 13,468 units · $86,850 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Angeliq — the program that covers self-administered drugs. 1 manufacturer.
⚠️ 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 Angeliq. 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
$103.4K
Claims incl. refills
277
Beneficiaries
199
Spend / beneficiary
$519.63
Spend / claim
$373.31
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 Per unit Per pack Marketing startStatus
50419-0482-03 3 BLISTER PACK in 1 CARTON (50419-482-03) / 28 TABLET, FILM COATED in 1 BLISTER PACK (50419-482-01) $6.37 / ea $535.19 2012-02-29 Active
50419-0482-72 You're viewing this 1 BLISTER PACK in 1 CARTON (50419-482-72) / 14 TABLET, FILM COATED in 1 BLISTER PACK (50419-482-71) — — 2012-02-29 Active

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

Pack size FAQ

What quantity is in NDC 50419-0482-72?
NDC 50419-0482-72 is a 14-count package — 1 blister pack in 1 carton / 14 tablet, film coated in 1 blister pack.
What NDC number is used to bill for this package of Angeliq drospirenone and estradiol .5 mg; .25 mg Tablet, Film Coated?
Bill NDC 50419-0482-72 — the 11-digit billing format is 50419048272. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

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

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 50419-482-72, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 50419-0482-72, written without dashes as 50419048272. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 50419-0482-72, the first segment (50419) is the labeler code FDA assigned to Bayer HealthCare Pharmaceuticals Inc.; the middle segment (0482) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (72) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Bayer HealthCare Pharmaceuticals Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 28 tablets (50419-0482-03). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Bayer HealthCare Pharmaceuticals Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 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 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning ~3 min read ▾

WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions (5.1) , and Clinical Studies (14.5) ].

The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.4) , Use in Specific Populations (8.5) , and Clinical Studies (14.5) ]. Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.4) , Clinical Studies (14.4 , 14.5) ].

Breast Cancer The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.3) , and Clinical Studies (14.4) ] . Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of 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 progestin 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 progestin therapy, taking into account her individual risk profile. Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.3) ] .

Cardiovascular Disorders and Probable Dementia The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg)-alone, relative to placebo [see Warnings and Precautions (5.1) , and Clinical Studies (14.5) ]. The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo.

It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.4) , Use in Specific Populations (8.5) , and Clinical Studies (14.5) ] . Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.4) and Clinical Studies (14.4 , 14.5) ]. Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI.

Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known…

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE 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. Angeliq is a combination of an estrogen and progestin indicated in a woman with a uterus for the treatment of: Moderate to severe vasomotor symptoms due to menopause.

( 1.1 ) Moderate to severe vulvar and vaginal atrophy symptoms due to menopause. ( 1.2 ) Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy, first consider the use of topical vaginal products.

1.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Angeliq 0.25 mg drospirenone (DRSP)/0.5 mg estradiol (E2) is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause in a woman with a uterus. Angeliq 0.5 mg DRSP/1 mg E2 is indicated for the treatment of moderate to severe vasomotor symptoms associated due to menopause in a woman with a uterus.

1.2Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Angeliq 0.5 mg DRSP/1 mg E2 is indicated for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause in a woman with a uterus.

⏱️ Dosage and Administration ~1 min read ▾

2 DOSAGE AND ADMINISTRATION Each pack of Angeliq covers 28 days of treatment. Treatment is continuous, which means that the next pack follows immediately without a break. The tablets are to be swallowed whole with some liquid irrespective of food intake and should preferably be taken at the same time every day.

In case a tablet is forgotten, it should be taken as soon as possible. If more than 24 hours have elapsed, the missed tablet should not be taken. If several tablets are forgotten, bleeding may occur.

Women who do not take estrogens or women who change from a continuous combination product may start treatment at any time. Women changing from a continuous sequential or cyclic hormone therapy (HT) should complete the current cycle of therapy before initiating Angeliq therapy. Start therapy with Angeliq 0.25 mg drospirenone (DRSP)/0.5 mg estradiol (E2) once daily for the treatment of moderate to severe vasomotor symptoms due to menopause.

Dosage adjustment should be guided by the clinical response ( 2.1 ) Start therapy with Angeliq 0.5 mg DRSP/1 mg E2 once daily for the treatment of moderate to severe vulvar and vaginal atrophy due to menopause ( 2.2 )

2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause One Angeliq 0.25 mg DRSP/0.5 mg E2 tablet or one Angeliq 0.5 mg DRSP/1 mg E2 tablet taken by mouth once daily.

2.2Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause One Angeliq 0.5 mg DRSP/1 mg E2 tablet taken by mouth once daily. Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy, first consider the use of topical vaginal products.

💊 Dosage Forms and Strengths 57 words ▾

3 DOSAGE FORMS AND STRENGTHS Angeliq 0.25 mg DRSP/0.5 mg E2 Tablets: round, biconvex, yellow, film-coated, embossed with a "EL" inside a hexagon Angeliq 0.5 mg DRSP/1 mg E2 Tablets : round, biconvex, pink, film-coated, embossed with a "CK" inside a hexagon Tablet: 0.25 mg DRSP/0.5 mg E2 and 0.5 mg DRSP/1 mg E2 ( 3 )

⛔ Contraindications ~1 min read ▾

4 CONTRAINDICATIONS Angeliq is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.3) ] . Breast cancer or a history of breast cancer [see Warnings and Precautions (5.3) ]. Estrogen-dependent neoplasia [see Warnings and Precautions (5.3) ].

Active DVT, PE or history of these conditions [see Warnings and Precautions (5.1) ]. Active arterial thromboembolic disease (for example, stroke and MI) or history of these conditions [see Warnings and Precautions (5.1) ]. Renal Impairment [see Warnings and Precautions (5.2) , Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ].

Hepatic impairment or disease [see Warnings and Precautions (5.10) , Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Adrenal insufficiency [see Warnings and Precautions (5.2) ]. Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders Known anaphylactic reaction, angioedema, or hypersensitivity to Angeliq or any of its ingredients [see Adverse Reactions (6.2) ] Undiagnosed abnormal genital bleeding ( 4 , 5.3 ) Breast cancer or a history of breast cancer ( 4 , 5.3 ) Estrogen-dependent neoplasia ( 4 , 5.3 ) Active DVT, PE, or a history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke and MI), or history of these conditions ( 4 , 5.1 ) Renal impairment ( 4 , 5.2 ) Hepatic impairment or disease ( 4 , 5.2 ) Adrenal insufficiency ( 4 , 5.2 ) Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 ) Known anaphylactic reaction, angioedema, or hypersensitivity to Angeliq ( 4 , 5.16 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Do not use with conditions that predispose to hyperkalemia (

5.2Estrogens increase the risk of gallbladder disease ( 5.5 ) Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.6 , 5.7 , 5.9 , 5.10 ) Monitor thyroid function in women on thyroid hormone replacement therapy ( 5.11 , 5.19 )

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/or obesity) and/or venous thromboembolism (VTE) [for example, personal history or family history of VTE, obesity, 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 (14.4) ] .

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 CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 strokes per 10,000 women-years).

The increase in risk was demonstrated in year one and persisted 1 [see Clinical Studies (14.4) ] . 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 (14.4) ] .

The WHI estrogen-alone substudy reported no overall effect on CHD events in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies (14.4) ] . Subgroup analyses of women 50 to 59 years of age, who were less than 10 years since menopause, suggest a reduction (not statistically significant) in CHD events in those women receiving daily CE (0.625 mg)-alone compared to placebo (8 versus 16 per 10,000 women-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 even…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning , Warnings and Precautions (5.1) ] Malignant Neoplasms [see Boxed Warning , Warnings and Precautions (5.3) ] The most common adverse reactions with Angeliq that occurred in at least 1% of users in clinical trials are: gastrointestinal and abdominal pain, female genital tract bleeding, breast pain and discomfort, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. From clinical trials with different dose formulations of Angeliq containing E2 dose ranging from 0.5 mg to 1.0 mg combined with DRSP dose ranging from 0.25 mg to 3 mg: The most common adverse reactions were gastrointestinal and abdominal pain, female genital bleeding, breast pain and headache.

The frequencies of common adverse reactions, in general, were higher for the Angeliq dose formulation containing E2 1 mg compared to Angeliq containing E2 0.5 mg. The most common adverse reactions leading to drug discontinuation in controlled clinical trials were abdominal pain, headache, postmenopausal bleeding, breast tenderness, and weight increased. Placebo-Controlled Trial: In a placebo-controlled trial evaluating Angeliq 0.25 mg DRSP/0.5 mg E2, 183 postmenopausal women received at least one dose of DRSP 0.25 mg/0.5 mg E2 and 180 received placebo.

Study participants were treated for 3 cycles of 28 days each for a total of 12 weeks of treatment. The median age was 53 years (range: 40-77 years) and over 50% of women had a hysterectomy, 68% were Caucasian and 24% were Black. Table 1 summarizes adverse reactions reported in at least 2% of women receiving Angeliq 0.25 mg DRS/0.5 mg E2 and at a higher incidence than subjects receiving placebo.

Table 1: Adverse Reactions that Occurred at a Frequency of ≥ 2% with Angeliq 0.25 mg DRSP/0.5 mg E2 and at a Higher Incidence than Placebo Adverse Reaction Angeliq (0.25 mg DRSP/0.5 mg E2) N=183 (100%) n (%) Placebo N=180 (100%) n (%) Gastrointestinal and abdominal pains Gastrointestinal and abdominal pain includes: abdominal pain (overall, lower, and upper), abdominal discomfort, abdominal tenderness 11 (6.0) 5 (2.8) Headache 11 (6.0) 9 (5.0) Vulvovaginal fungal infections 10 (5.5) 1 (0.6) Breast pain Breast pain includes: breast pain, breast tenderness, nipple pain 6 (3.3) 1 (0.6) Nausea 6 (3.3) 2 (1.1) Diarrhea 4 (2.2) 1 (0.6) Peripheral Edema 4 (2.2) 2 (1.1) Pooled data of clinical trials with different dose formulations of Angeliq: Data from 13 clinical trials in postmenopausal women treated with different dose formulations of Angeliq containing 1 mg E2 (1 mg E2 + 0.5 mg – 3.0 mg DRSP; N=2842) were pooled to provide an overall estimate of adverse reactions.

Similarly, data from 2 clinical trials with Angeliq containing 0.5 mg E2 (0.5 mg E2 + DRSP 0.25 mg – 0.5 mg; N=853) were pooled for the same purpose. Table 2 shows adverse reactions reported in at least 1% of women treated with Angeliq. Table 2: Adverse Reactions that Occurred at a Frequency of ≥ 1% in Clinical Trials Adverse Reaction Angeliq containing 1 mg E2 N = 2842 n (%) Angeliq containing 0.5 mg E2 N=853 n (%) Breast pain or discomfort 508 (17.9) 53 (6.2) Female genital tract bleeding 397 (14.0) 21 (2.5) Gastrointestinal and abdominal pain 186 (6.5) 31 (3.6) Cervical polyp 34 (1.2) 3 (0.4) Emotional lability 35 (1.2) 11 (1.3) Migraine 28 (1.0) 5 (0.6) Adverse Reactions in clinical studies were coded using the MedDRA dictionary (version 13.0).

Different MedDRA terms representing the same medical phenomenon have been grouped to…

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS Inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. ( 7.1 ) Serum potassium concentration may increase in women taking drospirenone with other drugs that have the potential to increase potassium. ( 7.1 )

7.1Metabolic Interactions Effect of Drospirenone on Other Drugs The potential effect of DRSP on CYP2C19 activity was investigated in a clinical pharmacokinetic study using omeprazole as a marker substrate. No significant effect of DRSP on the systemic clearance of the CYP3A4 product omeprazole sulfone was found. These results demonstrated that DRSP did not inhibit CYP2C19 and CYP3A4 in vivo .

Two further clinical drug-drug interaction studies using simvastatin and midazolam as marker substrates for CYP3A4, respectively, were performed and the results of these studies demonstrated that pharmacokinetics of the CYP3A4 substrates were not influenced by steady-state DRSP concentrations. Co-administration of DRSP and drugs that may increase serum potassium: There is a potential for an increase in serum potassium in women taking DRSP with other drugs that may affect electrolytes, such as ACE inhibitors, angiotensin receptor blockers, or NSAIDs, more pronounced in diabetic women [see Warnings and Precautions (5.2) , and Clinical Pharmacology (12.3) ] .

Electrolytes were studied in postmenopausal women with hypertension and/or diabetes mellitus requiring an ACE inhibitor or angiotensin receptor blocker. After 28 days of exposure to 1 mg E2 and 3 mg DRSP (n=112) or placebo (n=118). The mean change from baseline in serum potassium was 0.11 mEq/L for the E2/DRSP group and 0.08 mEq/L for the placebo group.

None of the subjects with serum potassium concentrations ≥5.5 mEq/L had cardiovascular adverse events. A drug-drug interaction study of DRSP 3 mg/E2 1 mg versus placebo was performed in mildly hypertensive postmenopausal women taking enalapril maleate 10 mg twice daily. Potassium concentrations were obtained every other day for a total of 2 weeks in all subjects.

Mean serum potassium concentrations in the DRSP/E2 treatment group relative to baseline were 0.22 mEq/L higher than those in the placebo group. On Day 14, the ratios for serum potassium C max and AUC in the DRSP/E2 group to those in the placebo group were 0.955 (90% CI: 0.914, 0.999) and 1.01 (90% CI: 0.944, 1.08), respectively. No woman in either treatment group developed hyperkalemia (serum potassium concentrations >5.5 mEq/L).

Of note, occasional or chronic use of NSAID medication was not restricted in any of the Angeliq clinical trials. Effect of Other Drugs on Estrogens and Progestins In vitro and in vivo studies have shown that estrogens and progestins are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.

In a clinical drug-drug interaction study conducted in premenopausal women, once daily co-administration of DRSP 3 mg/E2 1.5 mg containing tablets with strong CYP3A4 inhibitor, ketoconazole 200 mg twice daily for 10 days resulted in a moderate increase of exposure and a mild increase of peak concentration for DRSP. The E2 exposure and peak concentration were unaffected by ketoconazole, although the exposure and peak concentration of estrone (E1) increased. Although no clinically relevant effects on any safety or laboratory parameters including serum potassium were observed, this study only assessed women for 10 days.

The clinical impact for a woman taking a DRSP-containing combination hormone and chronic use of a CYP3A4/5 inhibitor is unknown. Substances decreasing the exposure and possibly diminishing the efficacy of estrogens and progestins (enzyme inducers) Inducers of CYP3A4 such as St. John's wort ( Hypericum perforatum ), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens and progestins, possibly resulting in a decrease in therapeutic effects and/…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Angeliq is not indicated for use in pregnancy . There are no data with the use of Angeliq in pregnant women, however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies or limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In reproduction studies in rats, rabbits and monkeys with oral administration of DRSP either as single compound or in combination with EE, no non-genital teratogenicity was observed.

Adverse developmental outcomes like an increase in fetal mortality and a retardation of fetal maturation were seen in rats and rabbits at exposures to DRSP exceeding the human exposure by a factor of >15 (in rats) or >60 (rabbits). Related to the antiandrogenic activity of drospirenone, a feminization of male fetuses and an impairment of male fertility was observed in rats (>150 times the human exposure to drospirenone) but not in monkeys (at up to more than 300 times the human exposure to drospirenone). Due to the large safety margins observed in the animal studies only a low likelihood of an increased risk for human pregnancy was concluded ( see Data ).

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. Data Animal Data In an embryo-fetal toxicity study in pregnant rats, DRSP was given from day 6 to 15 of gestation orally at doses of 5, 15 and 45 mg/kg/day, more than 60 times the human exposure starting from the low dose based on AUC of DRSP. A slight increase in postimplantational loss and a slight increase in retardation of fetal development (e.g. delayed ossification of bones of the feet) was seen in the two higher doses.

No teratogenicity was observed in rats. In an embryo-fetal study in rabbits, DRSP was given from day 6 to 18 of gestation orally at doses of 10, 30 and 100 mg/kg/day, about 20, 60 and 250 times the human exposure based on AUC. This resulted in a retardation of fetal development (delayed ossification of small bones, multiple fusions of ribs) at the high dose only and in an increase in fetal loss from the mid dose level.

No compound-related teratogenicity was seen in rabbits. In a further embryo-fetal toxicity study in pregnant rats, DRSP was orally administered in combination with ethinyl estradiol (100:1) from day 6 to 17 of gestation at doses of 1, 3 and 10 mg/kg/day DRSP, at about 1, 3 and 23 times the human exposure to DRSP on basis of AUC. Maternal toxicity (decreased body weight gain and food consumption) was seen starting at the low dose and an increase of early resorptions at the high dose level.

Skeletal variations and retardations were seen in fetuses at the high dose. No malformed fetuses and no effect on the external genitalia of the fetuses were observed. DRSP was administered with ethinyl estradiol (100:1) orally to pregnant rats during late pregnancy from day 14 to 21 of gestation (the period of genital development) at doses of 5, 15 and 45 mg/kg of DRSP, more than 60 times the human exposure starting from the low dose based on AUC of DRSP.

Maternal toxicity (decreased body weight gain) and fetal retardation (decreased fetal body weights) were seen starting at the low dose. There was a dose dependent increase in feminization of male rat fetuses starting at the mid dose level (that is, >150 times the human exposure to DRSP). DRSP was administered with ethinyl estradiol (100:1) orally to pregnant cynomolgus monkeys at doses up to 10 mg/kg DRSP, more than 300 times the human exposure based on AUC from day 20 to 90 of gestation.

A dose-dependent increase of abortions was observed. No teratogenic or feminization effects were seen in any dose group. DRSP was administered with ethinyl estradiol (100:1) in a peri-postnatal study in…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Angeliq is not indicated for use in pregnancy . There are no data with the use of Angeliq in pregnant women, however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies or limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In reproduction studies in rats, rabbits and monkeys with oral administration of DRSP either as single compound or in combination with EE, no non-genital teratogenicity was observed.

Adverse developmental outcomes like an increase in fetal mortality and a retardation of fetal maturation were seen in rats and rabbits at exposures to DRSP exceeding the human exposure by a factor of >15 (in rats) or >60 (rabbits). Related to the antiandrogenic activity of drospirenone, a feminization of male fetuses and an impairment of male fertility was observed in rats (>150 times the human exposure to drospirenone) but not in monkeys (at up to more than 300 times the human exposure to drospirenone). Due to the large safety margins observed in the animal studies only a low likelihood of an increased risk for human pregnancy was concluded ( see Data ).

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. Data Animal Data In an embryo-fetal toxicity study in pregnant rats, DRSP was given from day 6 to 15 of gestation orally at doses of 5, 15 and 45 mg/kg/day, more than 60 times the human exposure starting from the low dose based on AUC of DRSP. A slight increase in postimplantational loss and a slight increase in retardation of fetal development (e.g. delayed ossification of bones of the feet) was seen in the two higher doses.

No teratogenicity was observed in rats. In an embryo-fetal study in rabbits, DRSP was given from day 6 to 18 of gestation orally at doses of 10, 30 and 100 mg/kg/day, about 20, 60 and 250 times the human exposure based on AUC. This resulted in a retardation of fetal development (delayed ossification of small bones, multiple fusions of ribs) at the high dose only and in an increase in fetal loss from the mid dose level.

No compound-related teratogenicity was seen in rabbits. In a further embryo-fetal toxicity study in pregnant rats, DRSP was orally administered in combination with ethinyl estradiol (100:1) from day 6 to 17 of gestation at doses of 1, 3 and 10 mg/kg/day DRSP, at about 1, 3 and 23 times the human exposure to DRSP on basis of AUC. Maternal toxicity (decreased body weight gain and food consumption) was seen starting at the low dose and an increase of early resorptions at the high dose level.

Skeletal variations and retardations were seen in fetuses at the high dose. No malformed fetuses and no effect on the external genitalia of the fetuses were observed. DRSP was administered with ethinyl estradiol (100:1) orally to pregnant rats during late pregnancy from day 14 to 21 of gestation (the period of genital development) at doses of 5, 15 and 45 mg/kg of DRSP, more than 60 times the human exposure starting from the low dose based on AUC of DRSP.

Maternal toxicity (decreased body weight gain) and fetal retardation (decreased fetal body weights) were seen starting at the low dose. There was a dose dependent increase in feminization of male rat fetuses starting at the mid dose level (that is, >150 times the human exposure to DRSP). DRSP was administered with ethinyl estradiol (100:1) orally to pregnant cynomolgus monkeys at doses up to 10 mg/kg DRSP, more than 300 times the human exposure based on AUC from day 20 to 90 of gestation.

A dose-dependent increase of abortions was observed. No teratogenic or feminization effects were seen in any dose group. DRSP was administered with ethinyl estradiol (100:1) in a peri-postnatal study in rats from day 6 to 16 of gest…

🧒 Pediatric Use 22 words ▾

8.4Pediatric Use Angeliq is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing Angeliq to determine whether those over 65 years of age differ from younger women in their response to Angeliq. 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 Warnings and Precautions (5.1 , 5.3) and Clinical Studies (14.4) ] .

In the WHI estrogen-alone substudy (daily CE [0.625 mg] versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Warnings and Precautions (5.1) and Clinical Studies (14.4) ] . 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 (5.4) , and Clinical Studies (14.5) ] .

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 (5.4) , and Clinical Studies (14.5) ] .

🆘 Overdosage 41 words ▾

10 OVERDOSAGE Overdosage of estrogen plus progestogen may cause nausea and vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of Angeliq therapy with institution of appropriate symptomatic care.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol (E2) 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 in the 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 will 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 concentrations of these gonadotropins seen in postmenopausal women. DRSP is a synthetic progestin and spironolactone analog with antimineralocorticoid activity. In animals and in vitro , drospirenone has antiandrogenic activity, but no glucocorticoid, antiglucocorticoid, estrogenic, or androgenic activity.

Progestins counter estrogenic effects by decreasing the number of nuclear estradiol receptors and suppressing epithelial DNA synthesis in endometrial tissue.

12.2Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman's therapeutic response to Angeliq nor her risk for adverse outcomes. Likewise, exposure comparisons across different estrogen plus progestin products to infer efficacy or safety for the individual woman may not be valid.

12.3Pharmacokinetics Absorption Serum concentrations of DRSP reach peak concentrations approximately 1 hour after administration of Angeliq and mean absolute bioavailability of DRSP ranges from 76–85%. Following oral administration, the median T max of serum estradiol was approximately 2 hours after dosing with Angeliq and T max ranged between 0.3-10 hours. The pharmacokinetics of DRSP are dose proportional within the dose range of 0.25–4 mg.

Following daily dosing of Angeliq, steady state DRSP concentrations were observed after 10 days. Mean accumulation ratios for DRSP and estradiol were 2.3 and 2.0, respectively, following multiple doses of 0.5 mg DRSP/1 mg E2, and 2.6 and 1.6, respectively, following multiple doses of 0.25 mg DRSP/0.5 mg E2. Mean concentrations at 2 hours for DRSP ranged between 5.9 and 6.7 ng/mL after treatment with Angeliq (0.5 mg DRSP/1 mg E2) for 365 days.

Mean steady state serum DRSP and E2 concentrations are shown in Figure 1, and a summary of primary pharmacokinetic parameters following the administration of 0.25 mg DRSP/0.5 mg E2 or 0.5 mg DRSP/1 mg E2 at steady state is presented in Table 3. Figure 1: Mean (± SD) steady state serum drospirenone and estradiol concentrations following daily oral administration of 0.25 or 0.5 mg Drospirenone and 0.5 or 1 mg Estradiol 0.25 mg DRSP/0.5 mg E2 0.5 mg DRSP/1 mg E2 Table 3: Mean (± SD) Steady State Pharmacokinetic Parameters after Administration of Tablets Containing 0.25 or 0.5 mg Drospirenone and 0.5 or 1 mg Estradiol Parameter Unit 0.25 mg DRSP/0.5 mg E2 0.5 mg DRSP/1 mg E2 Drospirenone (DRSP) N=12 N=17 Except for T max , the mean PK results of DRSP, E2, and E1 are displayed as the arithmetic mean and standard deviation (SD, in parentheses).

For T max the median and range are provided. C max =Maximum observed serum concentration T max =time to reach C max AUC (0-24)…

🧬 Mechanism of Action ~1 min read ▾

12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol (E2) 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 in the 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 will 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 concentrations of these gonadotropins seen in postmenopausal women. DRSP is a synthetic progestin and spironolactone analog with antimineralocorticoid activity. In animals and in vitro , drospirenone has antiandrogenic activity, but no glucocorticoid, antiglucocorticoid, estrogenic, or androgenic activity.

Progestins counter estrogenic effects by decreasing the number of nuclear estradiol receptors and suppressing epithelial DNA synthesis in endometrial tissue.

📦 How Supplied / Storage and Handling 111 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Angeliq is supplied in packages of three blister packs: Angeliq 0.25 mg DRSP/0.5 mg E2 Angeliq 0.25 mg DRSP/0.5 mg E2 tablets are available as round, biconvex yellow film-coated tablets embossed with "EL" inside a hexagon. 3 blisters of 28 tablets NDC 50419-482-03 Angeliq 0.5 mg DRSP/1 mg E2 Angeliq 0.5 mg DRSP/1 mg E2 tablets are available as round, biconvex pink film-coated tablets embossed with "CK" inside a hexagon. 3 blisters of 28 tablets NDC 50419-483-03

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

📦 Storage and Handling 26 words ▾

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

📋 Description 162 words ▾

11 DESCRIPTION Angeliq tablets, for oral administration, provide a hormone regimen consisting of drospirenone and estradiol. Drospirenone, (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-1,3´,4´,6, 6a,7,8,9,10,11,12,13,14,15,15a,16-hexadecahydro-10,13-dimethylspiro-[17H-dicyclopropa[6,7:15,16]cyclopenta[a]phenanthrene- 17,2´(5H)-furan]-3,5´(2H)-dione (CAS) is a synthetic progestational compound and has a molecular weight of 366.5 and a molecular formula of C 24 H 30 O 3 . Estradiol USP, (Estra-1,3,5(10)-triene-3,17-diol,17ß), has a molecular weight of 272.39 and the molecular formula is C 18 H 24 O 2 .

The structural formulas are as follows: The inactive ingredients in Angeliq 0.5 mg DRSP/1 mg E2 tablets are: lactose monohydrate NF, corn starch NF, pregelatinized starch NF, povidone 25000 USP, magnesium stearate NF, hydroxylpropylmethyl cellulose USP, macrogol 6000 NF, talc USP, titanium dioxide USP, and red ferric oxide pigment NF. The inactive ingredients in Angeliq 0.25 mg DRSP/0.5 mg E2 tablets are: lactose monohydrate NF, corn starch NF, pregelatinized starch NF, povidone 25000 USP, magnesium stearate NF, hydroxylpropylmethyl cellulose USP, macrogol 6000 NF, talc USP, titanium dioxide USP, and yellow ferric oxide pigment NF.

Chemical Structure

💬 Information for Patients 119 words ▾

17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-Approved patient labeling (Patient Information). Abnormal Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see Warning and Precautions (5.3) ]. 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 Warning and Precautions (5.1 , 5.3 , 5.4) ].

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 [see Adverse Reactions (6) ].

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