LILETTA Levonorgestrel 52 mg Intrauterine Device, 1 intrauterine
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Progestin class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Levonorgestrel intrauterine system (Liletta, Kyleena, Mirena, Skyla) is used to prevent pregnancy. Levonorgestrel intrauterine system (Liletta, Mirena) is also used to treat heavy menstrual bleeding in women who want to use an intrauterine system to prevent pregnancy. Levonorgestrel is in a class of medications called hormonal contraceptives. Levonorgestrel intrauterine system works by thinning the lining of the uterus (womb) to prevent pregnancy from developing, thickening the mucus at the cervix (entrance to the uterus) to prevent sperm from entering, and preventing sperm from moving and su...
Read the full MedlinePlus article ↗- They both contain levonorgestrel, but they work very differently. The IUS (like Mirena, Liletta, Kyleena, or Skyla) is a small device a provider places inside your uterus that slow...
- What's the difference between the IUS and the emergency contraceptive pill — are they the same thing?
- The sooner the better — you should take it within 72 hours (3 days) of unprotected sex. It becomes less effective the longer you wait, so don't delay. If you vomit within 2 hours o...
- How quickly do I need to take the emergency contraceptive tablet after sex?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Levonorgestrel — tap one for details:
Levonorgestrel may be associated with lower levels of 2 nutrients — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 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.
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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?
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?
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $864.37 | $864.37 / 1 intrauterine |
| Medicare drug plans payPart D · Q2 2026 | $1,001.74 | $1,001.74 / 1 intrauterine |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Liletta 52 mgthis 00023-5858-01 | Allergan, | 1 intrauterine | — | — | FDA listed | — |
| Mirena 52 mg 50419-0423-01 | Bayer | 1 intrauterine | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
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.
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.
🛈 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.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 10028858 ↗ | Method of use | U-2348 | Mar 22, 2034 |
| US 11090186 ↗ | Method of use | U-2348 | Oct 24, 2033 |
| US 12004992 ↗ | Drug substance | — | Oct 6, 2033 |
| US 11571328 ↗ | Drug product | — | Sep 7, 2040 |
| Code | What it grants | Expires |
|---|---|---|
| I-917 | New indication (3-year) | Jun 29, 2026 |
Is there a generic version of LILETTA 52 MG SYSTEM?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00023-5858-01 You're viewing this | 1 TRAY in 1 CARTON (0023-5858-01) / 1 INTRAUTERINE DEVICE in 1 TRAY | 2016-05-31 | Active |
🧭 About this NDC listing & data coverage
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 |
Questions about this listing
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Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
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Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE LILETTA is a progestin-containing intrauterine system indicated for: Prevention of pregnancy for up to 8 years ( 1.1 ) Treatment of heavy menstrual bleeding for up to 5 years in patients who choose intrauterine contraception as their method of contraception ( 1.2 )
1.1Contraception LILETTA is indicated for prevention of pregnancy for up to 8 years.
1.2Heavy Menstrual Bleeding LILETTA is indicated for the treatment of heavy menstrual bleeding for up to 5 years in patients who choose to use intrauterine contraception as their method of contraception; replace after the end of the fifth year if continued treatment of heavy menstrual bleeding is needed.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The initial release rate of levonorgestrel (LNG) is approximately 20 mcg/day and declines progressively to approximately 6.5 mcg/day after 8 years; LILETTA can be removed at any time but must be removed by the end of the eighth year. ( 2.1 ) To be inserted into the uterine cavity with the provided inserter by a trained healthcare professional using strict aseptic technique. Follow insertion instructions exactly as described.
( 2.3 ) Re-examination and evaluation should be considered 4 to 6 weeks after insertion and during routine care, or more often if clinically indicated. ( 2.5 ) Figure 1a Figure 1b Figure 2 Figure 3 Figure 4 Figure 5 Figure 6: Close-up of Hemispherical Dome at Tip of Tube Figure 7 Figure 8 Figure 9: Releasing and Opening the Arms of the IUS Figure 10: Move LILETTA into the Fundal Position Figure 11: Releasing LILETTA from the Inserter Tube Figure 12 Figure 13 Figure 14: Removal of LILETTA 2. 1 Dosing Over Time LILETTA contains 52 mg of levonorgestrel (LNG).
Initially, LNG is released in vivo at a rate of approximately 20 mcg/day. This rate decreases progressively to approximately 6.5 mcg/day after 8 years. The average in vivo release rate of LNG is approximately 13.5 mcg/day over a period of 8 years.
For contraception, remove LILETTA by the end of the eighth year. LILETTA can be replaced at the time of removal with a new LILETTA if continued contraceptive protection is desired. For treatment of heavy menstrual bleeding, replace LILETTA by the end of the fifth year if continued use is needed.
2.2Timing of Insertion Refer to Table 1 for instructions on when to start use of LILETTA. Table 1: When to Insert LILETTA Starting LILETTA in patients not currently using hormonal or intrauterine contraception LILETTA can be inserted any time there is reasonable certainty the patient is not pregnant. Consider the possibility of ovulation and conception prior to initiation of LILETTA [see Contraindications ( 4 )] .
If LILETTA is inserted after the first 7 days of the menstrual cycle, the patient should use a barrier method of contraception (such as condoms) or abstain from vaginal intercourse for 7 days after insertion to prevent pregnancy. Switching to LILETTA from an oral, transdermal , or vaginal hormonal contraceptive LILETTA may be inserted at any time during the hormone-free interval of the previous method. If LILETTA is inserted during active use of the previous method, continue that method for 7 days after LILETTA insertion or until the end of the current treatment cycle.
If using continuous hormonal contraception, discontinue that method 7 days after LILETTA insertion. Switching to LILETTA from an injectable progestin contraceptive LILETTA may be inserted at any time. If LILETTA is inserted more than 3 months (13 weeks) after the last injection, the patient should use a barrier method of contraception (such as condoms) or abstain from vaginal intercourse for 7 days after insertion to prevent pregnancy.
Switching to LILETTA from a contraceptive implant or another IUS Insert LILETTA on the same day the implant or IUS is removed. This switch to LILETTA may be at any time during the menstrual cycle. Back-up contraception is not needed.
Inserting LILETTA after pregnancy After f irst-trimester abortion or miscarriage LILETTA may be inserted immediately after a first-trimester surgical or completed medical abortion or miscarriage, unless it is a septic abortion [ see Contraindications ( 4 )] . Back-up contraception is not needed. After childbirth or second-trimester abortion or miscarriage If immediate, insert LILETTA after expulsion/removal of the placenta, unless infection is present. [See Contraindication ( 4 ), Warnings and Precautions ( 5.5 , 5.6 ), Adverse Reactions ( 6.1 )] Back-up contraception is not needed.
If not immediate: Delay inserting LILETTA a minimum of 4 weeks or until the uterus is fully involuted [see Warnings and Precautions ( 5.5 , 5.6 ) , Adverse Reactions ( 6.1 ) ]…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS LILETTA is a levonorgestrel-releasing intrauterine system consisting of a T-shaped polyethylene frame with a drug reservoir containing 52 mg levonorgestrel, packaged within a sterile inserter. One intrauterine system consisting of a T-shaped polyethylene frame with a drug reservoir containing 52 mg LNG, packaged within a sterile inserter. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS LILETTA is contraindicated when one or more of the following conditions exist: Pregnancy [see Use in Specific Populations ( 8.1 ) ] For use as post-coital contraception (emergency contraception) Congenital or acquired uterine anomaly, including leiomyomas, that distorts the uterine cavity and would be incompatible with correct IUS placement [see Warnings and Precautions ( 5.10 )] Acute pelvic inflammatory disease (PID) [see Warnings and Precautions ( 5.4 )] Postpartum endometritis or infected abortion in the past 3 months [see Warnings and Precautions ( 5.2 , 5.4 )] Known or suspected uterine or cervical malignancy Known or suspected breast cancer or other hormone-sensitive cancer, now or in the past [see Warnings and Precautions ( 5.9 )] Uterine bleeding of unknown etiology [see Warnings and Precautions ( 5.10 )] Untreated acute cervicitis or vaginitis, including bacterial vaginosis, known chlamydial or gonococcal cervical infection, or other lower genital tract infections until infection is controlled [see Warnings and Precautions ( 5.4 )] 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 IUS that has not been removed A history of hypersensitivity reaction to any component of LILETTA.
Reactions may include rash, urticaria, and angioedema [see Adverse Reactions ( 6.2 )] . Pregnancy ( 4 ) Use for post-coital contraception (emergency contraception) ( 4 ) Congenital or acquired uterine anomaly that distorts the uterine cavity and would be incompatible with correct IUS placement ( 4 ) Acute pelvic inflammatory disease (PID) ( 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 hormone-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 infections ( 4 ) A previously inserted IUS that has not been removed ( 4 ) Hypersensitivity to any component of LILETTA ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Remove LILETTA if pregnancy occurs with LILETTA in place and LILETTA is in the uterus. 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 ) Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of LNG-releasing IUSs; strict aseptic technique is essential during insertion.
( 5.3 ) Before using LILETTA, consider the risks of pelvic infection. ( 5.4 ) Perforation may occur and reduce contraceptive effectiveness or require surgery. Risk is increased if inserted in patients who have fixed retroverted uteri, are postpartum, or are lactating.
( 5.5 ) Partial or complete expulsion may occur. ( 5.6 ) Evaluate persistent enlarged ovarian follicles or ovarian cysts. ( 5.7 ) Bleeding patterns can become altered, may remain irregular, and amenorrhea may ensue.
( 5.8 )
5.1Ectopic Pregnancy Evaluate patients for ectopic pregnancy if they become pregnant with LILETTA in place because the likelihood of a pregnancy being ectopic is increased with use of an IUS. Approximately half of pregnancies that occur with an IUS 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 new onset bleeding in an amenorrheic patient.
If an ectopic pregnancy is confirmed, LILETTA should be removed. The incidence of ectopic pregnancy in the clinical study on contraception with LILETTA, which excluded participants with a history of ectopic pregnancy who did not have a subsequent intrauterine pregnancy, was approximately 0.12 per 100 women-years. There were no ectopic pregnancies in the clinical study on heavy menstrual bleeding with LILETTA.
The risk of ectopic pregnancy in patients who have a history of ectopic pregnancy and use LILETTA is unknown. Patients with a previous history of ectopic pregnancy, tubal surgery, or pelvic infection have a higher risk of ectopic pregnancy. Ectopic pregnancy may require surgery and may result in loss of fertility.
Patients who use LILETTA should be informed about recognizing the signs and symptoms of ectopic pregnancy and promptly reporting them to their healthcare professional, and about the associated risks of ectopic pregnancy (e.g., loss of fertility).
5.2Intrauterine Pregnancy If pregnancy occurs while using LILETTA, determine if LILETTA is in the uterus. If LILETTA is in the uterus, attempt to remove LILETTA because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal of LILETTA or probing of the uterus may also result in spontaneous abortion.
In the event of an intrauterine pregnancy with LILETTA, consider the following: Septic A bortion If a patient becomes pregnant with an IUS in place, septic abortion—potentially including septicemia, septic shock, and death—may occur. Septic abortion typically requires hospitalization and treatment with intravenous antibiotics. Septic abortion may result in spontaneous abortion or a medical indication for pregnancy termination.
Should severe infection of the uterus occur, hysterectomy may be required, which will result in permanent infertility. LILETTA is contraindicated in patients who have had an infected abortion in the prior 3 months. Continuation of P regnancy If a patient becomes pregnant with LILETTA in place and if LILETTA cannot be removed or the patient chooses not to have it removed, warn the patient that failure to remove LILETTA increases the risk of miscarriage, sepsis, premature labor, and premature delivery.
Prenatal care should include counseling about these risks and instructions to immediately report any flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge or leakage of fluid, or any other symptom that suggests complications of the pregna…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious or 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 or Endometritis [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 in clinical studies (> 10% participants) are vulvovaginal mycotic infections, vaginal bacterial infections, acne, and nausea or vomiting.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Study Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The data described below reflect exposure of 1,751 generally healthy participants, 16 to 45 years of age, to LILETTA in a large, multi-center contraceptive study conducted in the US. Participants included 1,401 exposed for 1 year and 380 who completed 8 years of use; 58% were nulliparous (mean age 25.1 ± 4.3 years) and 42% were parous (mean age 30.3 ± 6.1 years).
Most participants who received LILETTA were Caucasian (78.4%) or Black/African American (13.3%); 14.7% of participants were of Hispanic ethnicity. Mean BMI of LILETTA participants was 26.9 kg/m 2 (range 15.8 – 61.6 kg/m 2 ); 25.1% had a BMI ≥ 30 kg/m 2 of which 5.3% had a BMI ≥ 40 kg/m 2 . The data cover more than 80,221 28-day cycles of LILETTA exposure.
The frequencies of reported adverse drug reactions represent crude incidences. The most common adverse reactions during the LILETTA clinical study on contraception (occurring in ≥ 5% of participants) are shown in Table 6. The most common adverse reactions during the first year of use were acne (11.4%), bacterial vaginitis (9.0%), and vulvovaginal mycotic infection (7.9%).
Table 6: Adverse Reactions in ≥ 5% of LILETTA Participants in the Phase 3 Clinical Study on Contraception Adverse Reaction % LILETTA Participants (N = 1 , 751) Vulvovaginal mycotic infections 20.2% Vaginal bacterial infections 19.2% Acne 15.5% Nausea or vomiting 10.5% Headache 10.1% Breast tenderness or pain 10.1% Abdominal discomfort or pain 10.0% Dyspareunia 9.6% Anxiety 9.6% Depression 9.1% Pelvic discomfort or pain 8.7% Dysmenorrhea 7.3% Mood changes 6.5% Back pain 6.5% Weight increased 6.1% Vaginal discharge 5.8% In the clinical study, 20.1% of LILETTA participants discontinued prematurely due to an adverse reaction.
The most common adverse reactions reported by participants as reason for discontinuation were expulsion (4.1%), bleeding complaints (2.5%), acne (1.4%), dysmenorrhea (1.0%), weight increased (1.0%), mood swings (0.8%), uterine spasm (0.7%), dyspareunia (0.6%) and pelvic pain (0.6%). Two participants discontinued the clinical study due to PID and one due to endometritis. The most common adverse reactions reported by participants as reason for discontinuation during the first year of use were expulsion (2.9%) and acne (0.7%).
In the clinical study, serious adverse reactions related to LILETTA were ectopic pregnancies, ovarian cysts, and IUS perforation requiring laparoscopic surgery. In the LILETTA clinical study on heavy menstrual bleeding, which included 105 participants who were 18- to 50-years old, the adverse reaction profile was consistent with the adverse reaction profile for LILETTA participants in the contraception study as shown in Table 6. Approximately 11% of LILETTA study participants discontinued prematurely due to an advers…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No drug-drug interaction studies have been conducted with LILETTA.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary LILETTA is contraindicated for use in pregnant patients and LILETTA may cause adverse pregnancy outcomes. If a patient becomes pregnant with LILETTA in place, there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery. Published studies report no harmful effects on fetal development associated with long-term use of contraceptive doses of oral progestins in a pregnant patient.
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 LILETTA. The background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.
8.2Lactation Ris k 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. Isolated cases of decreased milk production have been reported with another LNG-releasing IUS.
There are no reports of adverse effects in breastfed infants with maternal use of progestin-only contraceptives. The infant’s developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LILETTA, underlying maternal conditions, and any potential adverse effects from LILETTA on the infant. The incidence of uterine perforation appears higher in lactating patients [ s ee Warnings and Precautions ( 5.5 )] .
8.3Females and Males of Reproductive Potential Pregnancy Testing Assess pregnancy status prior to inserting LILETTA, as recommended [see Dosage and Administration ( 2.2 ) and Use in Specific Populations ( 8.1 )].
8.4Pediatric Use Safety and effectiveness of LILETTA have been established in females of reproductive potential. The safety and effectiveness are expected to be the same for postpubertal females under the age of 16 as for users 16 years and older. The LILETTA clinical study on contraception included 11 participants who were 16 to 17 years of age; no differences in safety or effectiveness were identified in these participants through 8 years of use of LILETTA.
Use of this product is not indicated before menarche.
8.5Geriatric Use LILETTA is not indicated in patients after menopause and has not been studied in this population.
8.6Hepatic Impairment No studies were conducted to evaluate the effect of hepatic disease on the disposition of LNG released from LILETTA [ see Contraindications ( 4 ) ].
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary LILETTA is contraindicated for use in pregnant patients and LILETTA may cause adverse pregnancy outcomes. If a patient becomes pregnant with LILETTA in place, there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery. Published studies report no harmful effects on fetal development associated with long-term use of contraceptive doses of oral progestins in a pregnant patient.
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 LILETTA. The background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of LILETTA have been established in females of reproductive potential. The safety and effectiveness are expected to be the same for postpubertal females under the age of 16 as for users 16 years and older. The LILETTA clinical study on contraception included 11 participants who were 16 to 17 years of age; no differences in safety or effectiveness were identified in these participants through 8 years of use of LILETTA.
Use of this product is not indicated before menarche.
🧓 Geriatric Use ▾
8.5Geriatric Use LILETTA is not indicated in patients after menopause and has not been studied in this population.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The local mechanism by which continuously released LNG provides contraception has not been conclusively demonstrated. Studies of LNG-releasing IUSs suggest several mechanisms for pregnancy prevention: prevention of fertilization due to the thickening of the cervical mucus, which inhibits sperm passage through the cervix, and inhibition of sperm mobility and function (capacitation), and alteration of the endometrium.
12.2Pharmacodynamics LILETTA has mainly local progestogenic effects in the uterine cavity which change the endometrium and may lead to alterations in the menstrual bleeding pattern [ see Warnings and Precautions ( 5.8 ) ] . High local concentrations of LNG lead to morphological changes including stromal pseudo-decidualization, glandular atrophy, a leukocytic infiltration, and a decrease in glandular and stromal mitoses. In clinical studies with other LNG-releasing IUSs with an LNG release rate similar to LILETTA, approximately 45-75% of menstrual cycles were ovulatory.
12.3Pharmacokinetics Absorption Low doses of LNG are administered into the uterine cavity with the LILETTA intrauterine delivery system. The initial in vivo release rate is 20.4 mcg/day and decreases to 17.7 mcg/day at 1 year, 15.3 mcg/day at 2 years, 13.3 mcg/day at 3 years, 11.5 mcg/day at 4 years, 10.0 mcg/day at 5 years, 8.7 mcg/day at 6 years, 7.5 mcg/day at 7 years, and 6.5 mcg/day at 8 years. In the clinical study on contraception, systemic plasma LNG concentrations were assessed in a subset of participants through Month 30 and in all participants in the study at Month 36 and after.
Plasma LNG concentrations following insertion of LILETTA are shown in Table 7. Table 7: Plasma LNG Concentrations (mean ± SD, pg/mL) Following LILETTA Insertion 7 Days (n=40) 6 Months (n=36) 12 Months (n=33) 24 Months (n=30) 36 Months (n=914) 48 Months (n=793) 60 Months (n=608) 72 Months (n=243) 84 Months (n=211) 96 Months (n=142) 252±123 195±68 168±51 150±47 132±54 114±52 101±42 92±43 90±38 88±37 Distribution The apparent volume of distribution of LNG at steady-state following oral administration is reported to be approximately
1.8L/kg. It is about 98.9% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin. Elimination The elimination half-life of LNG after a single oral administration is approximately 13.9 ± 3.2 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 conjugated at the 17β-OH position to form sulfate conjugates and, to a lesser extent, glucuronide conjugates in serum. Significant amounts of conjugated and unconjugated 3α, 5β-tetrahydrolevonorgestrel are also present in serum, along with much smaller amounts of 3α, 5α-tetrahydrolevonorgestrel and 16β-hydroxylevonorgestrel.
In vitro studies have demonstrated that oxidative metabolism of LNG is catalyzed by CYP enzymes, especially CYP3A4. Excretion 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 Rac ial or Ethnic Groups : The effect of race on plasma LNG concentrations after LILETTA insertion was assessed in 731 (80%) White participants, 106 (12%) Black participants, 40 (4%) Asian participants, 8 (1%) American Indian/Alaska Native participants, and 21 (2%) multiple-race participants.
Race does not appear to affect LNG concentrations following LILETTA insertion [see Clinical Studies ( 14 )] . BMI/Body Weight : The effect of BMI on LNG exposure was assessed in 687 non-obese (BMI < 30 kg/m 2 ) and 225 obese participants (BMI ≥ 30 kg/m 2 ). Plasma LNG concentrations were approximately 21-34% lower in obese participants than in non-obese participants based on data collected from Months 36 to…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The local mechanism by which continuously released LNG provides contraception has not been conclusively demonstrated. Studies of LNG-releasing IUSs suggest several mechanisms for pregnancy prevention: prevention of fertilization due to the thickening of the cervical mucus, which inhibits sperm passage through the cervix, and inhibition of sperm mobility and function (capacitation), and alteration of the endometrium.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING LILETTA (levonorgestrel-releasing intrauterine system), containing 52 mg levonorgestrel, is supplied partially preloaded within the inserter and packaged in a clear plastic tray with lid. LILETTA is available in a carton of one sterile unit. NDC # 0023-5858-01.
LILETTA is supplied sterile. LILETTA is sterilized with ethylene oxide. Do not re-sterilize.
Do not use if the packaging is damaged, or if the packaging is opened. Insert before the end of the month shown on the packaging. Store at 20°C – 25°C (68°F – 77°F), with excursions permitted between 15°C – 30°C (59°F – 86°F) [See USP Controlled Room Temperature].
Store the sealed tray with peel-off lid in outer carton until use to protect from light.
📋 Description ▾
11 DESCRIPTION the following structural formula: Levonorgestrel USP, (-)-13-ethyl-17-hydroxy-18,19-dinor-17-pregn-4-en-20-yn-3-one, the active ingredient in LILETTA, is the levorotatory form of norgestrel, which consists of a racemic mixture of D-(–)-norgestrel (levonorgestrel) and L-(+)-norgestrel (dextronorgestrel). It has a molecular weight of 312.45, a molecular formula of C21H28O2. Figure 15 Figure 16
11.1LILETTA LILETTA (levonorgestrel-releasing intrauterine system) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release rate of 20.4 mcg/day of levonorgestrel. Levonorgestrel USP, (-)-13-ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one, the active ingredient in LILETTA, is the levorotatory form of norgestrel, which consists of a racemic mixture of D-(–)-norgestrel (levonorgestrel) and L-(+)-norgestrel (dextronorgestrel). It has a molecular weight of 312.45, a molecular formula of C 21 H 28 O 2 , and the following structural formula: LILETTA consists of a T-shaped polyethylene frame (T-frame) with a drug reservoir around the vertical stem (Figure 15).
The T-frame has a loop at one end of the vertical stem and two horizontal arms at the other end. The drug reservoir consists of a cylinder, made of a mixture of 52 mg levonorgestrel and polydimethylsiloxane (PDMS) formed from silicone base, tetra-n-propyl silicate, and stannous octoate. The drug reservoir is covered by a translucent PDMS membrane.
The low-density polyethylene of the T-frame is compounded with barium sulfate, which makes it radio-opaque. A blue polypropylene monofilament removal thread is attached to an eyelet at the end of the vertical stem of the T-frame. The polypropylene of the removal thread contains a copper-containing pigment as a colorant.
The components of LILETTA, including its packaging, are not manufactured using natural rubber latex. Figure 15 : Diagram of LILETTA
11.2Inserter The inserter device provided with LILETTA is a single-use, disposable, sterile insertion system (tube, flange, handle; Figure 16), partially preloaded with the IUS product for intrauterine administration. Once LILETTA has been inserted, the inserter is discarded. Figure 16 : Diagram of Inserter
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling ( Patient Information ). Advise patients that this product does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs). Advise patients about the risks of ectopic pregnancy, including the loss of fertility.
Advise them to recognize and report promptly to their healthcare professional any symptoms of ectopic pregnancy, including lower abdominal pain, especially in association with missed periods [see Warnings and Precautions ( 5.1 )]. Advise patients about the following concerns and precautions if pregnancy occurs while using LILETTA: LILETTA will likely need to be removed because leaving it in place may increase the risk of spontaneous abortion and preterm labor; however, removal of LILETTA or probing of the uterus may also result in spontaneous abortion [see Warnings and Precautions ( 5.2 )].
Report promptly to their healthcare professional any symptoms that suggest complications of the pregnancy, including flu-like symptoms, fever, chills, cramping, pain, bleeding, and vaginal discharge or leakage of fluid [see Warnings and Precautions ( 5.2 )]. Septic abortion may occur. Advise them that if LILETTA cannot be removed or they choose not to have it removed, there may be an increased risk of miscarriage, sepsis, premature labor, and premature delivery [see Warnings and Precautions ( 5.2 )].
Advise patients that severe infection or sepsis, including Group A streptococcal sepsis (GAS), can occur within the first few days after LILETTA is inserted. Advise them to contact a healthcare professional immediately if they develop severe pain or fever shortly after LILETTA is inserted [see Warnings and Precautions ( 5.3 )]. Advise patients about the possibility of PID or endometritis and that these infections can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death.
Advise the patient to recognize and report to their healthcare professional any of the following signs and symptoms of possible infection [see Warnings and Precautions ( 5.4 )] : lower abdominal or pelvic pain or tenderness fever chills unusual or malodorous vaginal discharge atypical or unexplained bleeding (prolonged or heavy bleeding) genital lesions or sores. dyspareunia Advise patients that perforation may occur, most often during insertion, although the perforation may not be detected until sometime later. Perforation may also occur at any time during IUS use.
Advise them that if perforation occurs, LILETTA will have to be located and removed. Surgery may be required. Advise them that delayed detection or removal of LILETTA in case of perforation may have the following results [see Warnings and Precautions ( 5.5 )]: migration of IUS outside the uterus intestinal perforations adhesions intestinal obstruction peritonitis erosion of adjacent viscera abscesses loss of contraceptive protection Review with patients the signs and symptoms of LILETTA expulsion.
Advise patients on how they can check that the threads still protrude from their cervix, and not to pull on them. Advise them that there is no contraceptive protection if LILETTA is displaced or expelled [see Warnings and Precautions ( 5.6 )]. Advise patients that excessive pain or vaginal bleeding during insertion, worsening pain or bleeding after insertion, or the inability to feel the threads may occur with perforation and expulsion [see Warnings and Precautions ( 5.5 , 5.6 )].
Advise patients regarding the risk of ovarian cysts and that cysts can cause clinical symptoms including pelvic pain, abdominal pain or dyspareunia and infrequently will need surgery [see Warnings and Precautions ( 5.7 )]. Advise patients that irregular or prolonged bleeding and spotting, and/or cramps may occur during the first three to six months after insertion. If their symptoms continue or are severe, they should report them to their healthcare…