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Kyleena Levonorgestrel 19.5 mg Intrauterine Device, 1 intrauterine — NDC 50419-0424-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Kyleena Levonorgestrel 19.5 mg Intrauterine Device, 1 intrauterine — NDC 50419-424-01 (Billing 50419-0424-01)

by Bayer HealthCare Pharmaceuticals Inc. · 1 INTRAUTERINE DEVICE in 1 CARTON

This is a package of 1 intrauterine of Kyleena Levonorgestrel 19.5 mg Intrauterine Device from Bayer HealthCare Pharmaceuticals Inc., marketed since Sep 2016 and currently FDA-listed. It is the main listing for this product, which comes in 3 package sizes.

NDC 50419-0424-01
🏷️ FDA NDC (as labeled) 50419-424-01 billing pads the product segment with a zero
This package
Contains1 intrauterine Medicaid pays$1,254.95 / unit · 12 mo Per package$1,254.95 / 1 intrauterine · Medicaid Pack sizes3 compare ↓
Also priced by: Part D plans $1,241.36/unit — full pricing hub ↓
Main listing for product 50419-424 · Also comes in: 1 intrauterine 50419-424-08 1 intrauterine 50419-424-71
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

NDC database record

One package, one record: these facts belong to NDC 50419-424-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
50419 labeler · 424 product · 01 package
Package marketed since
Sep 19, 2016
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
1 EA per package
Barcode (UPC-A, from the NDC)
3 5041942401 1
Medicaid fills, this package
21,008 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 50419-424-01
Product NDC 50419-424
11-digit billing NDC 50419042401
NCPDP billing unit EA — each (per item)
RxCUI 1811886, 1856546
UNII 5W7SIA7YZW
Application # NDA208224
SPL Set ID 2e07c155-21e1-4781-9633-ce8bddd47080
Established class (EPC) Progestin; Progestin-containing Intrauterine System
Physiologic effect Inhibit Ovum Fertilization
Chemical class Progesterone Congeners
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2016-09-19
Route INTRAUTERINE
Dosage form INTRAUTERINE DEVICE
Substance LEVONORGESTREL

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

GPI-14 25200050005313
GPI class Kyleena
GCN Seq No 076612
GCN 42304
HICL code 007318
Ingredient (HICL) Levonorgestrel
HIC1 code X
Therapeutic class — broad (HIC1) Medical Supplies And Devices
HIC2 code X1
Therapeutic class — intermediate (HIC2) Reproductive System Agents
HIC3 code X1C
Therapeutic class — specific (HIC3) Intra-Uterine Devices (Iuds)
AHFS code 68:12.00.00
AHFS class Contraceptives
FDB label name KYLEENA 19.5 MG SYSTEM
FDB brand name Kyleena
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 076612
  • GCN: 42304
  • GPI-14 (Medi-Span): 25200050005313
  • HICL (First Databank): 007318
  • AHFS class code: 68:12.00.00
  • RxCUI (RxNorm): 1811886
Why two NDCs? The FDA registers this code as 50419-424-01 — 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 → 50419-0424-01. 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, Progestin-containing Intrauterine System
Drug family (ATC) Progestogens and estrogens, sequential preparations, Progestogens, Emergency contraceptives
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name KYLEENA 19.5 MG SYSTEM Ingredient Levonorgestrel
📗 Our plain-language guide HelloPharmacist
  • It comes in two main types. The intrauterine systems (Mirena, Liletta, Kyleena, Skyla) prevent pregnancy for years, and Mirena and Liletta also treat heavy menstrual bleeding. The...
  • Take it as soon as you can, within 72 hours (3 days) of unprotected sex. The sooner you take it, the better it works. If you vomit within 2 hours, call a healthcare professional to...
  • How do I take the emergency contraceptive tablet?
  • No. It's a backup method and isn't as effective as regular birth control. It also won't work if you're already pregnant, and it doesn't protect against HIV or other STDs.
📖 Read our full Levonorgestrel guide →
2
Nutrient depletion considerations

Levonorgestrel may be associated with lower levels of 2 nutrients — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Levonorgestrel nutrient depletion report →
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.

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 $1,254.95 $1,254.95 / 1 intrauterine
Medicare drug plans payPart D · Q2 2026 $1,241.36 $1,241.36 / 1 intrauterine
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
50419-0424-01 You're viewing this Main listing 1 INTRAUTERINE DEVICE in 1 CARTON 2016-09-19 — Active
50419-0424-08 50419-424-08 1 INTRAUTERINE DEVICE in 1 CARTON 2016-09-19 — Active
50419-0424-71 50419-424-71 1 INTRAUTERINE DEVICE in 1 CARTON Sample 2016-09-19 — Active

In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This package contains 1 intrauterine — 1 intrauterine device in 1 carton.
How does this package differ from NDC 50419-0424-08?
Both are Kyleena Levonorgestrel 19.5 mg Intrauterine Device — the drug itself is identical. This page's package is the 1 intrauterine one, while NDC 50419-0424-08 is the 1 intrauterine package.
What NDC number is used to bill for this package of Kyleena Levonorgestrel 19.5 mg Intrauterine Device?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Kyleena 19.5 mgthis 50419-0424-01 Bayer 1 intrauterine — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2016
First FDA approval
Sep 2016
📍
2026
Currently FDA-listed
10 years listed
🛡️
2029
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Sep 2029. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Sep 16, 2016 RLD RS ⏳ ~3 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 11850182 — method of use (U-3819)
US 10561524 — method of use (U-2948)
US 11628088 — drug product
2016 2018 2020 2022 2024 2026 2028
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 (3)
PatentTypeUse codeExpires
US 11850182 ↗ Method of use U-3819 Sep 14, 2029
US 10561524 ↗ Method of use U-2948 Sep 16, 2029
US 11628088 ↗ Drug product — Feb 7, 2027
Common questions
Is there a generic version of KYLEENA 19.5 MG SYSTEM?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for KYLEENA 19.5 MG SYSTEM. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Sep 2029 — an estimate, not a guaranteed launch date.
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.

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 25BB7EKE2E
    Barium sulfate is a white powder mineral compound used as a filler and opacifying agent in tablets and capsules. It adds bulk to the medicine and may be included in formulations for imaging purposes.
  • UNII 92RU3N3Y1O
    Dimethicone is a silicone-based oil that acts as an anti-foaming agent and lubricant in medicines. It reduces gas bubbles in liquid formulations and helps coat and protect the stomach lining when ingested.

2 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.

Manufacturer & labeler

LabelerBayer HealthCare Pharmaceuticals Inc.
Application holderBAYER HEALTHCARE PHARMACEUTICALS INC
FDA applicationNDA208224 (NDA)
Labeler code50419
First marketedSep 2016
Product typeHuman Prescription Drug
Portfolio62 products on file

More NDCs from Bayer HealthCare Pharmaceuticals Inc. labeler code 50419

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 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 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 46 words ▾

1 INDICATIONS AND USAGE Kyleena is indicated to prevent pregnancy for up to 5 years. Replace the system after 5 years if continued use is desired. Kyleena is a progestin-containing intrauterine system (IUS) indicated for prevention of pregnancy for up to 5 years. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Release rate of levonorgestrel (LNG) is 17.5 mcg/day after 24 days and declines to 7.4 mcg/day after 5 years; Kyleena must be removed or replaced after 5 years. ( 2.1 ) • To be inserted by a trained healthcare provider using strict aseptic technique. Follow insertion instructions exactly as described.

( 2.2 ) • Patient should be re-examined and evaluated 4 to 6 weeks after insertion; then yearly or more often if clinically indicated. ( 2.3 )

2.1Dosing Over Time Kyleena contains 19.5 mg of levonorgestrel (LNG) released in vivo at a rate of approximately 17.5 mcg/day after 24 days. This rate decreases progressively to 9.8 mcg/day after 1 year and to 7.4 mcg/day after 5 years. The average in vivo release rate of LNG is approximately 12.6 mcg/day over the first year and 9.0 mcg/day over a period of 5 years . [See Clinical Pharmacology ( 12.3 ).] Kyleena must be removed by the end of the fifth year and can be replaced at the time of removal with a new Kyleena if continued contraceptive protection is desired.

Kyleena can be physically distinguished from other intrauterine systems (IUSs) by the combination of the visibility of the silver ring on ultrasound and the blue color of the removal threads. Kyleena is supplied in a sterile package within an inserter that enables single-handed loading (see Figure 1). Do not open the package until required for insertion [see Description ( 11.2 )] .

Do not use if the seal of the sterile package is broken or appears compromised. Use strict aseptic techniques throughout the insertion procedure [see Warnings and Precautions ( 5.3 )] . Kyleena and Inserter 2.2.

Insertion Instructions • Obtain a complete medical and social history to determine conditions that might influence the selection of a levonorgestrel-releasing intrauterine system (LNG IUS) for contraception . If indicated, perform a physical examination and appropriate tests for any forms of genital or other sexually transmitted infections. [See Contraindications ( 4 ) and Warnings and Precautions ( 5.10 ).] Because irregular bleeding/spotting is common during the first months of Kyleena use, exclude endometrial pathology (polyps or cancer) prior to the insertion of Kyleena in women with persistent or uncharacteristic bleeding [see Warnings and Precautions ( 5.8 )] . • Follow the insertion instructions exactly as described to ensure proper placement and avoid premature release of Kyleena from the inserter.

Once released, Kyleena cannot be re-loaded . • Check expiration date of Kyleena prior to initiating insertion. • Kyleena should be inserted by a trained healthcare provider. Healthcare providers should become thoroughly familiar with the insertion instructions before attempting insertion of Kyleena. • Insertion may be associated with some pain and/or bleeding or vasovagal reactions (for example, syncope, bradycardia), or with seizure, especially in patients with a predisposition to these conditions. Consider administering analgesics prior to insertion.

Timing of Insertion Table 1: When to Insert Kyleena Starting Kyleena in women not currently using hormonal or intrauterine contraception • Insert Kyleena any time there is reasonable certainty that the woman is not pregnant. Consider the possibility of ovulation and conception prior to initiation of this product [see Contraindications ( 4 )]. • If Kyleena is inserted during the first seven days of the menstrual cycle or immediately after a first trimester abortion, back-up contraception is not needed. • If Kyleena is not inserted during the first seven days of the menstrual cycle, a barrier method of contraception should be used, or the patient should abstain from vaginal intercourse for seven days to prevent pregnancy.

Switching to Kyleena from an oral, transdermal or vaginal hormonal contraceptive • Insert Kyleena at any time, including during the hormone-free interval of the previous method. • If inserted during active use of the previous method, continue tha… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 61 words ▾

3 DOSAGE FORMS AND STRENGTHS Kyleena is a LNG-releasing IUS (a type of intrauterine device, or IUD) consisting of a T-shaped polyethylene frame with a steroid reservoir containing a total of 19.5 mg LNG. • One sterile intrauterine system consisting of a T-shaped polyethylene frame with a steroid reservoir containing 19.5 mg levonorgestrel, packaged within a sterile inserter ( 3 )

⛔ Contraindications ~2 min read ▾

4 CONTRAINDICATIONS The use of Kyleena is contraindicated when one or more of the following conditions exist: • Pregnancy or suspicion of pregnancy [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.1 )] • For use as post-coital contraception (emergency contraception) • Congenital or acquired uterine anomaly, including fibroids, that distorts the uterine cavity • Acute pelvic inflammatory disease (PID) or a history of PID unless there has been a subsequent intrauterine pregnancy [see Warnings and Precautions ( 5.4 )] • Postpartum endometritis or infected abortion in the past 3 months • Known or suspected uterine or cervical malignancy • Known or suspected breast cancer or other progestin-sensitive cancer, now or in the past • Uterine bleeding of unknown etiology • Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infections until infection is controlled • Acute liver disease or liver tumor (benign or malignant) • Conditions associated with increased susceptibility to pelvic infections [see Warnings and Precautions ( 5.4 )] • A previously inserted intrauterine device (IUD) that has not been removed • Hypersensitivity to any component of this product [see Adverse Reactions ( 6.2 ) and Description ( 11.1 )] • Pregnancy or suspicion of pregnancy.

Cannot be used for post-coital contraception (emergency contraception) ( 4 ) • Congenital or acquired uterine anomaly if it distorts the uterine cavity ( 4 ) • Acute pelvic inflammatory disease (PID) or a history of PID unless there has been a subsequent intrauterine pregnancy ( 4 ) • Postpartum endometritis or infected abortion in the past 3 months ( 4 ) • Known or suspected uterine or cervical malignancy ( 4 ) • Known or suspected breast cancer or other progestin-sensitive cancer ( 4 ) • Uterine bleeding of unknown etiology ( 4 ) • Untreated acute cervicitis or vaginitis or other lower genital tract infections ( 4 ) • Acute liver disease or liver tumor (benign or malignant) ( 4 ) • Increased susceptibility to pelvic infection ( 4 ) • A previous intrauterine device (IUD) that has not been removed ( 4 ) • Hypersensitivity to any component of Kyleena ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Remove Kyleena if pregnancy occurs with Kyleena in place. If pregnancy occurs, there is increased risk of ectopic pregnancy including loss of fertility, pregnancy loss, septic abortion (including septicemia, shock and death), and premature labor and delivery. ( 5.1 , 5.2 ) • Group A streptococcal infection has been reported following insertion of LNG IUS; strict aseptic technique is essential during insertion.

( 5.3 ) • Before using Kyleena, consider the risks of PID. ( 5.4 ) • Uterine perforation may occur and may reduce contraceptive effectiveness or require surgery. Risk is increased if inserted in lactating women and may be increased if inserted in women with fixed retroverted uteri and postpartum.

( 5.5 ) • Partial or complete expulsion may occur, which can be unnoticed, leading to loss of contraceptive efficacy. ( 5.6 ) • Evaluate persistent enlarged ovarian follicles or ovarian cysts. ( 5.7 ) • Bleeding patterns become altered, may remain irregular and amenorrhea may ensue.

( 5.8 ) • Kyleena can be safely scanned with MRI only under certain conditions. ( 5.11 )

5.1Risk of Ectopic Pregnancy Evaluate women for ectopic pregnancy if they become pregnant with Kyleena in place because the likelihood of a pregnancy being ectopic is increased with Kyleena. Approximately one-half of pregnancies that occur with Kyleena in place are likely to be ectopic. Also consider the possibility of ectopic pregnancy in the case of lower abdominal pain, especially in association with missed menses or if an amenorrheic woman starts bleeding.

The incidence of ectopic pregnancy in clinical trials with Kyleena, which excluded women with a history of ectopic pregnancy, was approximately 0.2% per year. The risk of ectopic pregnancy in women who have a history of ectopic pregnancy and use Kyleena is unknown. Women with a previous history of ectopic pregnancy, tubal surgery or pelvic infection carry a higher risk of ectopic pregnancy.

Ectopic pregnancy may result in loss of fertility.

5.2Risks with Intrauterine Pregnancy If pregnancy occurs while using Kyleena, remove Kyleena because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal of Kyleena or probing of the uterus may also result in spontaneous abortion. In the event of an intrauterine pregnancy with Kyleena, consider the following: Septic abortion In patients becoming pregnant with an IUS in place, septic abortion—with septicemia, septic shock, and death—may occur.

Continuation of pregnancy If a woman becomes pregnant with Kyleena in place and if Kyleena cannot be removed or the woman chooses not to have it removed, warn her that failure to remove Kyleena increases the risk of miscarriage, sepsis, premature labor and premature delivery. Advise her of isolated reports of virilization of the female fetus following local exposure to LNG during pregnancy with an LNG IUS in place [see Use in Specific Populations ( 8.1 )] . Follow her pregnancy closely and advise her to report immediately any symptom that suggests complications of the pregnancy.

5.3Sepsis Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of a LNG-releasing IUS. In some cases, severe pain occurred within hours of insertion followed by sepsis within days. Because death from GAS is more likely if treatment is delayed, it is important to be aware of these rare but serious infections.

Aseptic technique during insertion of Kyleena is essential in order to minimize serious infections such as GAS.

5.4Pelvic Infection Promptly examine users with complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding, fever, genital lesions or sores. Remove Kyleena in cases of recurrent endometritis or pelvic inflammatory disease, or if an acute pelvic infection is severe or does not respond to treatment. Pelvic Inflammatory Disease (PID) Kyleena is contraindicated in the presence of known or su… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling: • Ectopic Pregnancy [see Warnings and Precautions ( 5.1 )] • Intrauterine Pregnancy [see Warnings and Precautions ( 5.2 )] • Group A Streptococcal Sepsis (GAS) [see Warnings and Precautions ( 5.3 )] • Pelvic Inflammatory Disease [see Warnings and Precautions ( 5.4 )] • Perforation [see Warnings and Precautions ( 5.5 )] • Expulsion [see Warnings and Precautions ( 5.6 ] • Ovarian Cysts [see Warnings and Precautions ( 5.7 )] • Bleeding Pattern Alterations [see Warnings and Precautions ( 5.8 )] The most common adverse reactions reported (≥ 5% users) were vulvovaginitis, ovarian cysts, abdominal pain/pelvic pain, headache/migraine, acne/seborrhea, dysmenorrhea/uterine spasm, breast pain/breast discomfort, and increased bleeding.

( 6 ) 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 clinical practice. The data described below reflect exposure of 1,697 healthy 18 to 41-year-old women (mean age 27.8 ± 5.2 years) to Kyleena. These data come from two multi-center contraceptive trials: A phase 2 study with a 3-year duration was conducted in Europe enrolling generally healthy, 21 to 41-year old women; 217 subjects were exposed to Kyleena for one year and 174 completed three years.

The data in this trial cover approximately 8,000 cycles of exposure. A phase 3 study with a 3-year duration and an optional extension of Kyleena use up to 5 years was conducted in the United States (US), Canada, Europe, and Latin America. The population was generally healthy, 18 to 35-year old women.

A total of 1,208 subjects were exposed to Kyleena for at least one year; 707 women entered the optional extension phase after 3 years and 550 completed five years. The data in this trial cover approximately 60,000 cycles. In total for both studies, 1,425 subjects were exposed for at least 1 year, and 550 subjects completed 5 years of use.

Of the total of 1,697 subjects exposed to Kyleena, 563 were from the US and 1,134 were from Europe, Canada and Latin America; 623 (37%) were nulliparous (mean age 24.6 ± 4.5 years) and 1,074 (63%) were parous (mean age 29.7 ± 4.7 years). Most women who received Kyleena were Caucasian (83%) or Black/African American (4.4%); 9.4% of women were of Hispanic ethnicity. The clinical trials had no upper or lower weight or body mass index (BMI) limit.

Mean BMI of Kyleena subjects was 25.2 kg/m2 (range 15.2 – 57.6 kg/m2); 16% had a BMI ≥ 30 kg/m2, and 2.0% had a BMI ≥ 40 kg/m2. The frequencies of reported adverse drug reactions represent crude incidences. The most common adverse reactions (occurring in ≥ 5% users) were vulvovaginitis (24%), ovarian cyst (22%), abdominal pain/pelvic pain (21%), headache/migraine (15%), acne/seborrhea (15%), dysmenorrhea/uterine spasm (10%), breast pain/breast discomfort (10%), and increased bleeding (8%).

In the combined studies, 22% discontinued prematurely due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were increased bleeding (4.5%), abdominal pain/pelvic pain (4.2%), device expulsion (3.1%), acne/seborrhea (2.3%), and dysmenorrhea/uterine spasm (1.3%). Common adverse reactions (occurring in ≥1% users) are summarized in Table 4 (presented as crude incidences).

Table 4: Adverse reactions that occurred in at least 1% of Kyleena users in clinical trials by System Organ Class (SOC) System Organ Class Adverse Reaction Incidence (%) (N=1,697) Reproductive System and Breast Disorders Vulvovaginitis

24.3 Ovarian cyst a

22.2Dysmenorrhea/uterine spasm 8.0/2.4 Incr… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 72 words ▾

7 DRUG INTERACTIONS No drug-drug interaction studies have been conducted with Kyleena. Drugs or herbal products that induce or inhibit LNG metabolizing enzymes, including CYP3A4, may decrease or increase, respectively, the serum concentrations of LNG during the use of Kyleena. However, the contraceptive effect of Kyleena is mediated via the direct release of LNG into the uterine cavity and is unlikely to be affected by drug interactions via enzyme induction or inhibition.

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary The use of Kyleena is contraindicated in pregnancy or with a suspected pregnancy and Kyleena may cause adverse pregnancy outcomes [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 , 5.2 )]. If a woman becomes pregnant with Kyleena in place, the likelihood of ectopic pregnancy is increased and there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery . Remove Kyleena, if possible, if pregnancy occurs in a woman using Kyleena.

If Kyleena cannot be removed, follow the pregnancy closely [see Warnings and Precautions ( 5.1 , 5.2 )] . There have been isolated cases of virilization of the external genitalia of the female fetus following local exposure to LNG during pregnancy with an LNG IUS in place. Animal reproduction studies have not been conducted with Kyleena.

8.2Lactation Risk Summary Published studies report the presence of LNG in human milk. Small amounts of progestins (approximately 0.1% of the total maternal doses) were detected in the breast milk of nursing mothers who used other LNG-releasing IUSs, resulting in exposure of LNG to the breastfed infants. There are no reports of adverse effects in breastfed infants with maternal use of progestin-only contraceptives.

Isolated cases of decreased milk production have been reported with a LNG-releasing IUS. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Kyleena and any potential adverse effects on the breastfed child from Kyleena or from the underlying maternal condition.

8.3Females and Males of Reproductive Potential Return to Fertility After Discontinuing Kyleena About 71% of 163 women who desired pregnancy after study discontinuation and provided follow-up information, conceived within 12 months after removal of Kyleena.

8.4Pediatric Use Safety and efficacy of Kyleena have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal females under the age of 18 as for users 18 years and older. Use of this product before menarche is not indicated.

8.5Geriatric Use Kyleena has not been studied in women over age 65 and is not approved for use in this population.

🤰 Pregnancy 136 words ▾

8.1Pregnancy Risk Summary The use of Kyleena is contraindicated in pregnancy or with a suspected pregnancy and Kyleena may cause adverse pregnancy outcomes [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 , 5.2 )]. If a woman becomes pregnant with Kyleena in place, the likelihood of ectopic pregnancy is increased and there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery . Remove Kyleena, if possible, if pregnancy occurs in a woman using Kyleena.

If Kyleena cannot be removed, follow the pregnancy closely [see Warnings and Precautions ( 5.1 , 5.2 )] . There have been isolated cases of virilization of the external genitalia of the female fetus following local exposure to LNG during pregnancy with an LNG IUS in place. Animal reproduction studies have not been conducted with Kyleena.

🧒 Pediatric Use 47 words ▾

8.4Pediatric Use Safety and efficacy of Kyleena have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal females under the age of 18 as for users 18 years and older. Use of this product before menarche is not indicated.

🧓 Geriatric Use 22 words ▾

8.5Geriatric Use Kyleena has not been studied in women over age 65 and is not approved for use in this population.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The local mechanism by which continuously released LNG contributes to the contraceptive effectiveness of Kyleena has not been conclusively demonstrated. Studies of Kyleena and similar LNG IUS prototypes have suggested several mechanisms that prevent pregnancy: thickening of cervical mucus preventing passage of sperm into the uterus, inhibition of sperm capacitation or survival, and alteration of the endometrium .

12.2Pharmacodynamics Kyleena has mainly local progestogenic effects in the uterine cavity. The local concentrations of LNG lead to morphological changes including stromal pseudodecidualization, glandular atrophy, a leukocytic infiltration and a decrease in glandular and stromal mitoses. In clinical trials with Kyleena, ovulation was assessed based on serum progesterone values >2.5 ng/mL in one study and serum progesterone values >2.5 ng/mL together with serum estradiol levels <27.24 pg/mL in another study.

Evidence of ovulation by these criteria was seen in 23 out of 26 women in the first year, in 19 out of 20 women in the second year, and in all 16 women in the third year . In the fourth year, evidence of ovulation was observed in the one woman remaining in the subset and in the fifth year, no women remained in this subset.

12.3Pharmacokinetics Absorption Low doses of LNG are administered into the uterine cavity with the Kyleena intrauterine delivery system. The in vivo release rate is approximately 17.5 mcg/day after 24 days and is reduced to approximately 15.3 mcg/day after 60 days and to 9.8 mcg/day after 1 year. It then declines progressively to approximately 7.9 mcg/day after 3 years and 7.4 mcg/day after 5 years.

The average LNG in vivo release rate is approximately 12.6 mcg/day over the first year and 9.0 mcg/day over the period of 5 years. In a subset of 6 subjects, the maximum observed serum LNG concentration (mean ±SD) was 302 ± 170 pg/mL, reached after 7.5 days (median) of Kyleena insertion. Thereafter, the LNG serum concentrations (mean ±SD) at Year 1, 2, 3, 4 and 5 were 199 ± 171 pg/mL (N=6), 120 ± 57 pg/mL (N=6), 122 ± 65 pg/mL (N=6), 79 ± 12 pg/mL (N=3) and 65 ± 15 pg/mL (N=3), respectively.

A population pharmacokinetic evaluation based on a broader database (>1000 patients) showed a similar declining concentration profile, with 175 ± 74 pg/mL at 7 days after placement, 125 ± 50 pg/mL at 1 year, 99 ± 41 pg/mL after 3 years, and 90 ± 35 pg/mL after 5 years. Distribution The apparent volume of distribution of LNG is reported to be approximately

1.8L/kg. LNG is bound non-specifically to serum albumin and specifically to sex hormone binding globulin (SHBG). Accordingly, changes in the concentration of SHBG in serum result in an increase (at higher SHBG concentration) or a decrease (at lower SHBG concentration) of the total LNG concentration in serum.

In a subset of 6 subjects, the concentration of SHBG declined on average by about 30% during the first 3 months after insertion of Kyleena and remained relatively stable over the 5 year period of use. Less than 2% of the circulating LNG is present as free steroid. Elimination Following intravenous administration of 0.09 mg LNG to healthy volunteers, the total clearance of LNG is approximately 1 mL/min/kg and the elimination half-life is approximately 20 hours.

Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for wide individual variations in LNG concentrations seen in individuals using LNG–containing contraceptive products. Metabolism Following absorption, LNG is extensively metabolized. The most important metabolic pathways are the reduction of the Δ4-3-oxo group and hydroxylations at positions 2α, 1β and 16β, followed by conjugation.

Significant amounts of conjugated and unconjugated 3α, 5β- are also present in serum, along with much smaller amounts of 3α, 5α-tetrahydrolevonorgestrel and 16β-hydroxylevonorgestrel. CYP3A4 is the main enzyme involved in the… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 62 words ▾

12.1Mechanism of Action The local mechanism by which continuously released LNG contributes to the contraceptive effectiveness of Kyleena has not been conclusively demonstrated. Studies of Kyleena and similar LNG IUS prototypes have suggested several mechanisms that prevent pregnancy: thickening of cervical mucus preventing passage of sperm into the uterus, inhibition of sperm capacitation or survival, and alteration of the endometrium .

📦 How Supplied / Storage and Handling 81 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Kyleena (levonorgestrel-releasing intrauterine system), containing a total of 19.5 mg LNG, is available in a carton of one sterile unit. NDC# 50419-424-01 Kyleena is supplied sterile. Kyleena is sterilized with ethylene oxide.

Do not resterilize. For single use only. Do not use if the inner package is damaged or open.

Insert before the end of the month shown on the label. Store at 25°C (77°F); with excursions permitted between 15–30°C (59–86°F) [see USP Controlled Room Temperature].

📋 Description ~2 min read ▾

11 DESCRIPTION Kyleena (levonorgestrel-releasing intrauterine system) contains 19.5 mg of LNG, a progestin, and is intended to provide an initial release rate of approximately17.5 mcg/day of LNG after 24 days. Levonorgestrel USP, (-)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one, the active ingredient in Kyleena, has a molecular weight of 312.4, a molecular formula of C 21 H 28 O 2 , and the following structural formula:

11.1Kyleena Kyleena consists of a T-shaped polyethylene frame (T-body) with a steroid reservoir (hormone elastomer core) around the vertical stem. The white T-body has a loop at one end of the vertical stem and two horizontal arms at the other end. The reservoir consists of a whitish or pale yellow cylinder, made of a mixture of LNG and silicone (polydimethylsiloxane), containing a total of 19.5 mg LNG.

The reservoir is covered by a semi-opaque silicone membrane, composed of polydimethylsiloxane and colloidal silica. A ring composed of 99.95% pure silver is located at the top of the vertical stem close to the horizontal arms and is visible by ultrasound. The polyethylene of the T-body is compounded with barium sulfate, which makes it radiopaque.

A monofilament blue polypropylene removal thread is attached to a loop at the end of the vertical stem of the T-body. The polypropylene of the removal thread contains <0.5% phthalocyaninato(2-) copper as a colorant (see Figure 10). The components of Kyleena, including its packaging, are not manufactured using natural rubber latex.

Figure 10. Kyleena Kyleena

11.2Inserter Kyleena is packaged sterile within an inserter. The inserter (Figure 11), which is used for insertion of Kyleena into the uterine cavity, consists of a symmetric two-sided body and slider that are integrated with flange, lock, pre-bent insertion tube and plunger. The outer diameter of the insertion tube is 3.8 mm.

The vertical stem of Kyleena is loaded in the insertion tube at the tip of the inserter. The arms are pre-aligned in the horizontal position. The removal threads are contained within the insertion tube and handle.

Once Kyleena has been placed, the inserter is discarded. Figure 11. Diagram of Inserter Inserter Chem Diagram

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). • Sexually Transmitted Infections: Advise the patient that this product does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs). • Risk of Ectopic Pregnancy: Advise the patient about the risks of ectopic pregnancy, including the loss of fertility. Teach her to recognize and report to her healthcare provider promptly any symptoms of ectopic pregnancy. [See Warnings and Precautions ( 5.1 ).] • Risks of Intrauterine Pregnancy: Advise the patient to contact her healthcare provider if she thinks she might be pregnant.

Inform the patient about the risks of intrauterine pregnancy while using Kyleena, including the risks of leaving Kyleena in place and the risks of removing Kyleena or probing of the uterus. If Kyleena cannot be removed in a pregnant patient, advise her to report immediately any symptom that suggests complications of the pregnancy. Advise her of isolated reports of virilization of the female fetus following local exposure to LNG during pregnancy with an LNG IUS in place. [See Warnings and Precautions ( 5.2 ) and Use in Special Populations ( 8.1 ).] • Sepsis: Advise the patient that severe infection or sepsis, including Group A streptococcal sepsis (GAS), can occur within the first few days after Kyleena is inserted.

Instruct her to contact a healthcare provider immediately if she develops severe pain or fever shortly after Kyleena is inserted. [See Warnings and Precautions ( 5.3 ).] • Pelvic Infection: Advise the patient about the possibility of pelvic infections, including PID, and that these infections can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death. Teach patients to recognize and report to their healthcare provider promptly any symptoms of pelvic infection.

These symptoms include development of menstrual disorders (prolonged or heavy bleeding), unusual vaginal discharge, abdominal or pelvic pain or tenderness, dyspareunia, chills, and fever. [See Warnings and Precautions ( 5.4 ).] • Perforation and Expulsion: Advise the patient that the IUS may be expelled from or perforate the uterus and instruct her on how she can check that the threads still protrude from the cervix. Inform her that excessive pain or vaginal bleeding during Kyleena placement, worsening pain or bleeding after placement, or the inability to feel Kyleena strings may occur with Kyleena perforation and expulsion.

Caution her not to pull on the threads and displace Kyleena. Inform her that there is no contraceptive protection if Kyleena is displaced or expelled. Instruct the patient to contact her healthcare provider if she cannot feel the threads and to avoid intercourse or use a non-hormonal back-up birth control (such as condoms or spermicide) until the location of Kyleena has been confirmed.

Advise her that if perforation occurs, Kyleena will have to be located and removed; surgery may be required. [See Warnings and Precautions ( 5.5 , 5.6 , 5.10 ).] • Ovarian Cysts: Advise the patient regarding the risk of ovarian cysts and that cysts can cause clinical symptoms including pelvic pain, abdominal pain or dyspareunia. Advise the patient to contact her healthcare provider if she experiences these symptoms. [See Warnings and Precautions ( 5.7 ).] • Bleeding Pattern Alterations: Advise the patient that irregular or prolonged bleeding and spotting, and/or cramps may occur during the first few weeks after insertion.

Inform the patient that, during the first 6 months of Kyleena use, the number of bleeding and spotting days may be higher and bleeding patterns may be irregular. If her symptoms continue or are severe she should report them to her healthcare provider. [See Warnings and Precautions ( 5.8 ).] • Clinical Considerations for Use and Removal: Advise the patient to contact her healthcare provider if she experiences… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption Low doses of LNG are administered into the uterine cavity with the Kyleena intrauterine delivery system. The in vivo release rate is approximately 17.5 mcg/day after 24 days and is reduced to approximately 15.3 mcg/day after 60 days and to 9.8 mcg/day after 1 year. It then declines progressively to approximately 7.9 mcg/day after 3 years and 7.4 mcg/day after 5 years.

The average LNG in vivo release rate is approximately 12.6 mcg/day over the first year and 9.0 mcg/day over the period of 5 years. In a subset of 6 subjects, the maximum observed serum LNG concentration (mean ±SD) was 302 ± 170 pg/mL, reached after 7.5 days (median) of Kyleena insertion. Thereafter, the LNG serum concentrations (mean ±SD) at Year 1, 2, 3, 4 and 5 were 199 ± 171 pg/mL (N=6), 120 ± 57 pg/mL (N=6), 122 ± 65 pg/mL (N=6), 79 ± 12 pg/mL (N=3) and 65 ± 15 pg/mL (N=3), respectively.

A population pharmacokinetic evaluation based on a broader database (>1000 patients) showed a similar declining concentration profile, with 175 ± 74 pg/mL at 7 days after placement, 125 ± 50 pg/mL at 1 year, 99 ± 41 pg/mL after 3 years, and 90 ± 35 pg/mL after 5 years. Distribution The apparent volume of distribution of LNG is reported to be approximately

1.8L/kg. LNG is bound non-specifically to serum albumin and specifically to sex hormone binding globulin (SHBG). Accordingly, changes in the concentration of SHBG in serum result in an increase (at higher SHBG concentration) or a decrease (at lower SHBG concentration) of the total LNG concentration in serum.

In a subset of 6 subjects, the concentration of SHBG declined on average by about 30% during the first 3 months after insertion of Kyleena and remained relatively stable over the 5 year period of use. Less than 2% of the circulating LNG is present as free steroid. Elimination Following intravenous administration of 0.09 mg LNG to healthy volunteers, the total clearance of LNG is approximately 1 mL/min/kg and the elimination half-life is approximately 20 hours.

Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for wide individual variations in LNG concentrations seen in individuals using LNG–containing contraceptive products. Metabolism Following absorption, LNG is extensively metabolized. The most important metabolic pathways are the reduction of the Δ4-3-oxo group and hydroxylations at positions 2α, 1β and 16β, followed by conjugation.

Significant amounts of conjugated and unconjugated 3α, 5β- are also present in serum, along with much smaller amounts of 3α, 5α-tetrahydrolevonorgestrel and 16β-hydroxylevonorgestrel. CYP3A4 is the main enzyme involved in the oxidative metabolism of LNG. Excretion LNG and its phase I metabolites are excreted primarily as glucuronide conjugates.

About 45% of LNG and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates. Specific Populations Pediatric: Safety and efficacy of Kyleena have been established in women of reproductive age. Use of this product before menarche is not indicated.

Geriatric: Kyleena has not been studied in women over age 65 and is not approved for use in this population . Race: No studies have evaluated the effect of race on the pharmacokinetics of Kyleena. Hepatic Impairment: No studies were conducted to evaluate the effect of hepatic disease on the disposition of Kyleena .

Renal Impairment: No formal studies were conducted to evaluate the effect of renal disease on the disposition of Kyleena. Drug-Drug Interactions No drug-drug interaction studies were conducted with Kyleena [see Drug Interactions ( 7 )] .

🧬 Pharmacodynamics 137 words ▾

12.2Pharmacodynamics Kyleena has mainly local progestogenic effects in the uterine cavity. The local concentrations of LNG lead to morphological changes including stromal pseudodecidualization, glandular atrophy, a leukocytic infiltration and a decrease in glandular and stromal mitoses. In clinical trials with Kyleena, ovulation was assessed based on serum progesterone values >2.5 ng/mL in one study and serum progesterone values >2.5 ng/mL together with serum estradiol levels <27.24 pg/mL in another study.

Evidence of ovulation by these criteria was seen in 23 out of 26 women in the first year, in 19 out of 20 women in the second year, and in all 16 women in the third year . In the fourth year, evidence of ovulation was observed in the one woman remaining in the subset and in the fifth year, no women remained in this subset.

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES The contraceptive efficacy of Kyleena was evaluated in a clinical trial that enrolled generally healthy women aged 18–35, of whom 1,452 received Kyleena. Of these, 40% (574) were nulliparous women, 870 (60%) women completed 3 years of the study, 707 (49%) elected to enroll in an extension phase up to a total of 5 years, and 550 (38%) completed 5 years of use. The trial was a multicenter, multi-national, randomized, open-label study conducted in 11 countries in Europe, Latin America, the US and Canada.

Women less than six weeks postpartum, with a history of ectopic pregnancy, with clinically significant ovarian cysts or with HIV or otherwise at high risk for sexually transmitted infections were excluded. A total of 563 (39%) were treated at US sites and 889 (61%) were at non-US sites. The racial demographics of enrolled women who received Kyleena was: Caucasian (80%), Black/African American (5.1%), Other (2.6%) and Asian (1.2%); 11% indicated Hispanic ethnicity.

The clinical trial had no upper or lower weight or BMI limit. The weight range was 38 to 173 kg (mean weight: 68.7 kg) and mean BMI was 25.3 kg/m 2 (range 15.2–57.6 kg/m 2 ). Of Kyleena-treated women, 22% discontinued the study treatment due to an adverse reaction, 5.0% were lost to follow-up, 2.3% withdrew for unspecified reasons, 1.2% discontinued due to a protocol deviation, 0.9% discontinued due to pregnancy, and 20% discontinued due to other reasons.

The pregnancy rate calculated as the Pearl Index (PI) in women aged 18–35 years was the primary efficacy endpoint used to assess contraceptive reliability. The PI was calculated based on 28-day equivalent exposure cycles; evaluable cycles excluded those in which back-up contraception was used unless a pregnancy occurred in that cycle. The Year 1 PI was based on 2 pregnancies and the cumulative 5-year pregnancy rate was based on 13 pregnancies that occurred after the onset of treatment and within 7 days after Kyleena removal or expulsion.

Table 5 shows the calculated annual and cumulative pregnancy rates. Table 7: Pearl Indices by Year and 5-Year Cumulative Pregnancy Rate Kyleena Clinical Trial Pearl Index Cumulative 5-Year Kaplan Meier Rate Year 1 Year 2 Year 3 Year 4 Year 5 Number of Evaluable 28-day Cycles of Exposure 16,207 13,853 11,610 8,556 7,087 57,313 Pregnancy Rate (95% Confidence Interval) 0.16 (0.02, 0.58) 0.38 (0.10, 0.96) 0.45 (0.12, 1.15) 0.15 (0.00, 0.85) 0.37 (0.04, 1.33) 1.45 (0.82, 2.53)

🧪 Nonclinical Toxicology 16 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility [See Warnings and Precautions ( 5.9 ).]

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 13 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility [See Warnings and Precautions ( 5.9 ).]

📚 References 17 words ▾

15 REFERENCES 1 Centers for Disease Control and Prevention (CDC), (2019). CDC-STD Treatment [online] Available at: https://www.cdc.gov/std/treatment/default.htm

📄 Patient Package Insert ~3 min read ▾

Patient Package Insert Patient Information Kyleena (Ki-lee-nah) (levonorgestrel-releasing intrauterine system) Read this Patient Information carefully before you decide if Kyleena is right for you. This information does not take the place of talking with your gynecologist or other healthcare provider who specializes in women's health. If you have any questions about Kyleena, ask your healthcare provider.

You should also learn about other birth control methods to choose the one that is best for you. Kyleena does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs). What is Kyleena? • Kyleena is a hormone-releasing system placed in your uterus by your healthcare provider to prevent pregnancy for up to 5 years. • Kyleena can be removed by your healthcare provider at any time. • Kyleena can be used whether or not you have given birth to a child.

Kyleena is a small, flexible plastic T-shaped system that slowly releases a progestin hormone called levonorgestrel (LNG) that is often used in birth control pills. Because Kyleena releases LNG into your uterus, only small amounts of the hormone enter your blood. Kyleena does not contain estrogen.

Two thin threads are attached to the stem (lower end) of Kyleena. The threads are the only part of Kyleena you can feel when Kyleena is in your uterus; however, unlike a tampon string, the threads do not extend outside your body. Kyleena is small and Flexible What if I need birth control for more than 5 years?

Kyleena must be removed after 5 years. Your healthcare provider can place a new Kyleena during the same office visit if you choose to continue using Kyleena. What if I want to stop using Kyleena?

Kyleena is intended for use up to 5 years, but you can stop using Kyleena at any time by asking your healthcare provider to remove it. You could become pregnant as soon as Kyleena is removed, so you should use another method of birth control if you do not want to become pregnant. Talk to your healthcare provider about the best birth control methods for you, because your new method may need to be started 7 days before Kyleena is removed to prevent pregnancy.

What if I change my mind about birth control and want to become pregnant in less than 5 years? Your healthcare provider can remove Kyleena at any time. You may become pregnant as soon as Kyleena is removed.

About 7 out of 10 women who want to become pregnant will become pregnant sometime in the first year after Kyleena is removed. How does Kyleena work? Kyleena may work in several ways including thickening cervical mucus, inhibiting sperm movement, reducing sperm survival, and thinning the lining of your uterus.

It is not known exactly how these actions work together to prevent pregnancy. How well does Kyleena work for contraception? The following chart shows the chance of getting pregnant for women who use different methods of birth control.

Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.

Kyleena, an intrauterine device (IUD), also known as an intrauterine system (IUS), is in the box at the top of the chart. Who might use Kyleena? You might choose Kyleena if you: • want long-term birth control that provides a low chance of getting pregnant (less than 1 in 100) • want birth control that works continuously for up to 5 years • want birth control that is reversible • want a birth control method that you do not need to take daily • are willing to use a birth control method that is placed in the uterus • want birth control that does not contain estrogen Do not use Kyleena if you: • are or might be pregnant; Kyleena cannot be used as an emergency contraceptive • have a serious pelvic infection called pelvic inflammatory disease (PID) or have had PID in the past unless yo… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 6 words ▾

Dosage and Administration (2.4 ) 3/2023

📄 Package Label / Principal Display Panel 52 words ▾

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 50419-424-011 Sterile Unit Rx only www.kyleena.com IMPORTANT: To be inserted in the uterus by or under the supervision of a licensed clinician. See physician insert for detailed instructions for use. Kyleena (levonorgestrel-releasing intrauterine system) — 19.5 mg levonorgestrel — 1 sterile unit — intrauterine use Kyleena Carton

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

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 this package alone, 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 – Q1 2026 · 5 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
21K
Units reimbursed last 4 qtrs
20.8K
Gross reimbursed last 4 qtrs
$26.14M
Avg / prescription
$1,244.50
Avg / unit
$1,254.96
Latest quarter Q1 2026
4.3KRx
Fee-for-service vs managed care ⓘ
25% FFS 75% MCO
Fee-for-service · 5,326 Rx Managed care · 15,682 Rx
State Medicaid map
Alaska: 40 units · 5.5 per 100k residents AK Maine: 154 units · 11.0 per 100k residents ME Washington: 529 units · 6.8 per 100k residents WA Idaho: 261 units · 13.3 per 100k residents ID Montana: 169 units · 14.9 per 100k residents MT North Dakota: no data reported ND Minnesota: 513 units · 8.9 per 100k residents MN Wisconsin: 399 units · 6.8 per 100k residents WI Michigan: 442 units · 4.4 per 100k residents MI New York: 938 units · 4.8 per 100k residents NY Vermont: 69 units · 10.7 per 100k residents VT New Hampshire: 159 units · 11.3 per 100k residents NH Oregon: 458 units · 10.8 per 100k residents OR Nevada: 270 units · 8.5 per 100k residents NV Wyoming: 51 units · 8.7 per 100k residents WY South Dakota: 68 units · 7.4 per 100k residents SD Iowa: 313 units · 9.8 per 100k residents IA Illinois: 471 units · 3.8 per 100k residents IL Indiana: 496 units · 7.2 per 100k residents IN Ohio: 715 units · 6.1 per 100k residents OH Pennsylvania: 622 units · 4.8 per 100k residents PA New Jersey: 251 units · 2.7 per 100k residents NJ Massachusetts: 654 units · 9.3 per 100k residents MA California: 2,507 units · 6.4 per 100k residents CA Utah: 280 units · 8.2 per 100k residents UT Colorado: 615 units · 10.5 per 100k residents CO Nebraska: 284 units · 14.4 per 100k residents NE Missouri: 402 units · 6.5 per 100k residents MO Kentucky: 867 units · 19.2 per 100k residents KY West Virginia: 96 units · 5.4 per 100k residents WV Virginia: 814 units · 9.3 per 100k residents VA Maryland: 427 units · 6.9 per 100k residents MD Connecticut: 412 units · 11.4 per 100k residents CT Rhode Island: 108 units · 9.9 per 100k residents RI Arizona: 527 units · 7.1 per 100k residents AZ New Mexico: 196 units · 9.3 per 100k residents NM Kansas: 115 units · 3.9 per 100k residents KS Arkansas: 103 units · 3.4 per 100k residents AR Tennessee: 635 units · 8.9 per 100k residents TN North Carolina: 1,254 units · 11.6 per 100k residents NC South Carolina: 282 units · 5.2 per 100k residents SC Delaware: no data reported DE Oklahoma: 354 units · 8.7 per 100k residents OK Louisiana: 363 units · 7.9 per 100k residents LA Mississippi: 118 units · 4.0 per 100k residents MS Alabama: 157 units · 3.1 per 100k residents AL Georgia: 480 units · 4.4 per 100k residents GA D.C.: no data reported DC Hawaii: 78 units · 5.4 per 100k residents HI Texas: 891 units · 2.9 per 100k residents TX Florida: 426 units · 1.9 per 100k residents FL
Units reimbursed · per 100k residents
1.919.2
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 Kentucky 19.2 /100k
2 Montana 14.9 /100k
3 Nebraska 14.4 /100k
4 Idaho 13.3 /100k
5 North Carolina 11.6 /100k
6 Connecticut 11.4 /100k
7 New Hampshire 11.3 /100k
8 Maine 11.0 /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.

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.
1 intrauterine this page50419-0424-01 21,008 Rx · $26,144,381
1 intrauterine50419-0424-08 No Medicaid data
1 intrauterine50419-0424-71 No Medicaid data
Drug total (last 4 qtrs): 21,008 Rx · 20,833 units · $26,144,381 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 · 2025 (Q1-Q4)

Medicare Part D (outpatient prescription) spending for Kyleena — 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 Kyleena. 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.
Total Part D spend
$50.2K
Claims incl. refills
43
Beneficiaries
43
Spend / beneficiary
$1,167.12
Spend / claim
$1,167.12
💵 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.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Levonorgestrel — the ingredient across all brands.

Top reported reactions

Device Expulsion45,536
Device Dislocation20,447
Menstruation Irregular15,061
Vaginal Haemorrhage15,056
Genital Haemorrhage11,164
Abdominal Pain Lower9,317
Nausea8,806

Age at onset

Neonate87
Infant54
Child25
Adolescent1,518
Adult62,663
Elderly189

Reporter sex

206,325 reports

Serious outcomes

Death309
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 11,815 3,283
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

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) ✓ Available
“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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by 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 2 other package presentations of this same product, including 1 intrauterine (50419-0424-08), 1 intrauterine (50419-0424-71). 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.
← 50419-0423-01 · Bayer 50419-0451-04 · Bayer →
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.