LILETTA- levonorgestrel intrauterine device
Actavis Pharma, Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use LILETTA ® safely and effectively. See full prescribing information for LILETTA .
LILETTA (levonorgestrel-releasing intrauterine system)
Initial U.S. Approval: 2015
RECENT MAJOR CHANGES
INDICATIONS AND USAGE
LILETTA is a sterile, levonorgestrel-releasing intrauterine system indicated for prevention of pregnancy for up to 4 years. (1)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
WARNINGS AND PRECAUTIONS
The most common adverse reactions reported in clinical trials (> 10% users) are vaginal bacterial infections, vulvovaginal mycotic infections and acne. (6)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
Refer to Table 1 for instruction on when to start use of LILETTA.
|Starting LILETTA in women not currently using hormonal or intrauterine contraception
|Switching to Liletta from an oral, transdermal or vaginal hormonal contraceptive||
|Switching to LILETTA from an injectable progestin contraceptive||
|Switching to LILETTA from a contraceptive implant or another IUS||
|Inserting Liletta after abortion or miscarriage|
|Inserting Liletta after Childbirth
LILETTA (Figure 1) is provided in a sterile pouch [see Description (11)] and is inserted into the uterine cavity with the provided inserter (Figure 2) by carefully following the insertion instructions. 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)].
Figure 1 LILETTA Intrauterine Contraceptive System (IUS)
Figure 2: LILETTA IUS with Inserter
LILETTA should only be inserted by a trained healthcare provider. Healthcare providers should become thoroughly familiar with the product, product educational materials, product insertion instructions, prescribing information, and patient labeling before attempting insertion of LILETTA.
Planning for Insertion
• Local anesthesia, needle, and syringe
• Os finder and/or cervical dilators
• Ultrasound with abdominal probe
Use aseptic technique during the entire insertion procedure. Loading and inserting LILETTA can be done with or without sterile gloves. If not using sterile gloves, complete all steps for loading the IUS (Steps 1-7) inside the pouch. Maintain sterility during LILETTA insertion; do not touch LILETTA or parts of any sterile instrument that will pierce tissue (e.g., a tenaculum on the cervix) or go into the uterine cavity. If, at any step, there is a need to touch a sterile surface, sterile gloves should be used.
Preparation for Insertion
Loading the IUS into the Inserter
Figure 3: Place the LILETTA pouch on a flat surface.
If using sterile gloves, you can open the pouch completely before putting on the sterile gloves.
Figure 4: Release the threads from the flange and insert the rod.
Figure 7: Final IUS Positioning
ENSURE A HEMISPHERICAL DOME IS ACHIEVED.
When the IUS is in the correct position, the lower end of the tube will be aligned approximately at the upper edge of the upper indent on the rod.
Check to make sure the IUS is correctly loaded. You should note the following:
Remove the loaded IUS insertion tube from the pouch while holding the lower end of the tube firmly between your fingers and thumb.
If not using sterile gloves, do not touch the flange and any part of the insertion tube above the flange during this step and through the IUS insertion procedure.
IUS Insertion into the Uterus
Note: Fundal positioning is important to prevent expulsion.
Figure 10: After 10 – 15 seconds, advance to the fundus while holding both the rod and the tube.
Figure 11: Hold the rod still and pull back the tube to the ring on the rod.
Note: Ensure the tube is held firmly in place until the rod is completely pulled outside of the tube as there will be some slight resistance while removing the rod from the tube.
Figure 12: Cut the threads about 3 cm from the cervix
Insertion of LILETTA is now complete.
Important information to consider during or after insertion:
Re-examine and evaluate patients 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated. The healthcare provider should check strings during each routine and follow-up visit.
Timing of Removal
Planning for Removal
• Local anesthetic, needle, and syringe
• Os finder and/or cervical dilators
• Ultrasound with abdominal probe
• Sterile tenaculum
• Antiseptic solution
• Long, narrow forceps
Figure 13: Removal of LILETTA
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.
The use of LILETTA is contraindicated when one or more of the following conditions exist:
Evaluate women for ectopic pregnancy if they become pregnant with LILETTA in place because the likelihood of a pregnancy being ectopic is increased with LILETTA. Approximately half of pregnancies that occur with LILETTA 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 periods or if an amenorrheic woman starts bleeding. If an ectopic pregnancy is confirmed, LILETTA should be removed.
The incidence of ectopic pregnancy in the clinical trial with LILETTA, which excluded women with a history of ectopic pregnancy who did not have a subsequent intrauterine pregnancy, was approximately 0.16 per 100 women-years. The risk of ectopic pregnancy in women who have a history of ectopic pregnancy and use LILETTA is unknown. Women 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.
Tell women who choose LILETTA about the risks of ectopic pregnancy, including the loss of fertility. Teach them to recognize and report to their healthcare provider promptly any signs of ectopic 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:
In patients becoming pregnant with an IUS in place, septic abortion – with 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.
Continuation of pregnancy
If a woman becomes pregnant with LILETTA in place and if LILETTA cannot be removed or the woman chooses not to have it removed, warn her 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 that she should report immediately any flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge or leakage of fluid, or any other symptom that suggests complications of the pregnancy.
Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of other LNG-releasing IUSs. 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 LILETTA is essential in order to minimize serious infections such as GAS.
Insertion of LILETTA is contraindicated in the presence of known or suspected PID or endometritis or a history of PID unless there has been a subsequent intrauterine pregnancy [see Contraindications (4)]. IUSs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion.
In the clinical trial with LILETTA, pelvic infection was diagnosed in 0.8% of women. The infection was diagnosed as PID in 0.5% of women and as endometritis in 0.3% of women. One woman diagnosed with PID developed the infection within a week of LILETTA insertion, while the remainder were diagnosed more than six months after insertion. The cases of endometritis had onset less than 40 days after LILETTA insertion except for one occurring at 43 months after insertion.
Counsel women who receive LILETTA to notify a healthcare provider if they have complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding, fever, or genital lesions or sores. In such circumstances, perform a pelvic examination promptly to evaluate for possible pelvic infection. Remove LILETTA in cases of recurrent PID or endometritis, or if an acute pelvic infection is severe or does not respond to treatment.
Women at increased risk for PID or endometritis
PID and endometritis are often associated with a sexually transmitted infection (STI), and LILETTA does not protect against STIs. The risk of PID or endometritis is greater for women who have multiple sexual partners, and also for women whose sexual partner(s) have multiple sexual partners. Women who have had PID or endometritis are at increased risk for a recurrence or re-infection. In particular, ascertain whether the woman is at increased risk of infection (for example, leukemia, acquired immune deficiency syndrome [AIDS], IV drug abuse).
Asymptomatic PID or endometritis
PID or endometritis may be asymptomatic but still result in tubal damage and its sequelae.
Treatment of PID or endometritis
Following a diagnosis of PID or endometritis, or suspected PID or endometritis, perform appropriate testing for sexually transmitted infection and initiate antibiotic therapy promptly. LILETTA does not need to be removed immediately if the woman needs ongoing contraception (1). In the LILETTA clinical trial, 12 of the 14 women who developed PID or endometritis were successfully treated without removal of LILETTA.
Reassess the woman in 48-72 hours. If no clinical improvement occurs, continue antibiotics and consider removal of LILETTA. If the woman wants to discontinue use, remove LILETTA after antibiotics have been started to avoid the potential risk for bacterial spread resulting from the removal procedure. Guidelines for PID or endometritis treatment are available from the Centers for Disease Control (CDC), Atlanta, Georgia (1).
Actinomycosis has been associated with IUS use. Symptomatic women with known actinomycosis infection should have LILETTA removed and receive antibiotics. Actinomycetes can be found in the genital tract cultures in healthy women without IUSs. The significance of actinomyces-like organisms on Pap test in an asymptomatic IUS user is unknown, and so this finding alone does not always require LILETTA removal and treatment. When possible, confirm a Pap test diagnosis with cultures.
Partial or complete expulsion of LILETTA may occur, resulting in the loss of contraceptive protection. In the clinical trial with LILETTA, an overall expulsion rate of 3.7% was reported, with a rate of 2.1% in nulliparous women and 5.7% in parous women. Expulsion may be associated with symptoms of bleeding or pain, or it may be asymptomatic and go unnoticed. LILETTA typically decreases menstrual bleeding over time; therefore, an increase in menstrual bleeding may be indicative of an expulsion.
The risk of expulsion may be increased when the uterus is not completely involuted at the time of insertion. Delay LILETTA insertion a minimum of 6 weeks or until uterine involution is complete following a delivery or a second trimester abortion.
Remove a partially expelled LILETTA. If expulsion has occurred, a new LILETTA may be inserted within 7 days after the onset of a menstrual period after pregnancy has been ruled out.
Because the contraceptive effect of LILETTA is mainly due to its local effects within the uterus, ovulatory cycles with follicular rupture usually occur in women of fertile age using LILETTA. Sometimes atresia of the follicle is delayed and the follicle may continue to grow. Most ovarian cysts that occur during use of LNG-releasing IUSs are asymptomatic and disappear spontaneously during two to three months of observation. Cysts that cause clinical symptoms can result in pelvic or abdominal pain or dyspareunia. Symptomatic ovarian cysts occurred in 4.3% of subjects using LILETTA, and 0.3% of subjects discontinued use of LILETTA because of an ovarian cyst.
Evaluate persistent ovarian cysts. Surgical intervention is not usually required, but may be necessary in some cases. Discuss this risk with patients who choose to use LILETTA.
LILETTA can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea, and amenorrhea. During the first three to six months of LILETTA use, the number of bleeding and spotting days may be increased and bleeding patterns may be irregular. Thereafter, the number of bleeding and spotting days usually decreases but bleeding may remain irregular.
In the LILETTA clinical trial, amenorrhea developed in approximately 19% of LILETTA users by the end of the first year of use, in 27% by the end of the second year of use, in 37% by the end of the third year of use and 41% by the end of the fourth year of use. In the trial, 2.2% of LILETTA subjects discontinued due to bleeding complaints. Table 2 shows the bleeding and spotting days based on 28-day cycle equivalents.
|28-Day Cycle Equivalent||Cycle 1
|Days on treatment||1-28||85-112||169-196||337-364||674-728|
|Number of bleeding days||5.8||5.2||2.3||3.3||1.6||2.7||1.2||2.4||0.8||1.8|
|Number of spotting days||9.0||5.9||4.3||4.2||3.2||3.6||2.7||3.4||1.9||2.8|
Note: Includes all LILETTA subjects.
In the LILETTA clinical trial, 429 of 439 (97.7%) women evaluated experienced menses after LILETTA removal. Excluding nine women who became pregnant or had a hysterectomy before having a return of their menses, 429 of 430 (99.8%) had a return of their menses, 99.1% within three months.
If a significant change in bleeding develops during prolonged use, take appropriate diagnostic measures to rule out endometrial pathology. Consider the possibility of pregnancy if menstruation does not occur within six weeks of the onset of a previous menstruation. Once pregnancy has been excluded, repeated pregnancy tests are generally not necessary in amenorrheic women unless indicated, for example, by other signs of pregnancy or by pelvic pain.
Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception, including LILETTA, because some breast cancers are hormone-sensitive [see Contraindications (4)].
Spontaneous reports of breast cancer have been received during postmarketing experience with another LNG-releasing IUS. Observational studies have not provided consistent evidence of an increased risk of breast cancer with use of a LNG-releasing IUS.
Obtain a complete medical and social history, including partner status, to determine conditions that might influence the selection of an IUS for contraception.
Because irregular bleeding/spotting is common during the first months of LILETTA use, exclude endometrial pathology (polyps or cancer) prior to the insertion of LILETTA in women with persistent or uncharacteristic bleeding.
Special attention must be given to ascertaining whether the woman is at increased risk of infection (for example, leukemia, acquired immune deficiency syndrome [AIDS], IV drug abuse), or has a history of PID unless there has been a subsequent intrauterine pregnancy. LILETTA does not protect against HIV/STI transmission. [See Warnings and Precautions (5.4)].
Use LILETTA with caution after careful assessment if any of the following conditions exist, and consider removal of the IUS if any of them arise during use:
In addition, consider removing LILETTA if any of the following conditions arise during use [see Contraindications (4)]:
If the threads are not visible or are significantly shortened, they may have broken or retracted into the cervical canal or uterus. Consider the possibility that the IUS may have been displaced, (for example, expelled or perforated the uterus) [see Warnings and Precautions (5.5, 5.6)]. Exclude pregnancy and verify the location of LILETTA, for example, by sonography, by X-ray, or by gentle exploration of the cervical canal with a suitable instrument [see Dosage and Administration (2.6)]. If LILETTA is displaced, remove it. A new LILETTA may be inserted at that time or during the next menses if it is certain that conception has not occurred. If LILETTA is in place with no evidence of perforation, no intervention is indicated.
The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure of 1,751 generally healthy 16- to 45-year-old women to LILETTA in a large, multi-center contraceptive trial conducted in the US, including 1,409 exposed for 1 year and 837 subjects who completed 4 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 women who received LILETTA were Caucasian (78.4%) or Black/African American (13.3%); 14.7% of women were of Hispanic ethnicity. The clinical trial had no upper or lower weight or BMI limit. Mean BMI of LILETTA subjects was 26.9 kg/m2 (range 15.8 – 61.6 kg/m2); 25.1% had a BMI ≥ 30 kg/m2, of which 5.3% had a BMI ≥ 40 kg/m2. The data cover more than 59,000 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 trial (occurring in ≥ 5% of users) are shown in Table 3.
|System Organ Class/Preferred Term||% LILETTA Subjects (N = 1,751)|
|Vaginal bacterial infections||17.9%|
|Vulvovaginal mycotic infections||17.9%|
|Nausea or vomiting||9.4%|
|Breast tenderness or pain||8.0%|
|Pelvic discomfort or pain||7.9%|
|Abdominal discomfort or pain||7.4%|
In the contraceptive trial, 18.3% of LILETTA users discontinued prematurely due to an adverse reaction. The most common adverse reactions leading to discontinuation were expulsion (3.7%) and bleeding complaints (2.2%). The next most common adverse reactions causing discontinuation were acne (1.4%), dysmenorrhea (1.0%), weight increased (1.0%), mood swings (0.8%), uterine spasm (0.7%) and pelvic pain (0.6%). One woman discontinued the clinical study due to PID and one due to endometritis.
In the clinical trial, serious adverse reactions considered related or possibly related to LILETTA were ectopic pregnancies, ovarian cysts, and IUS perforation requiring a laparoscopic surgery.
The following adverse reactions have been identified during post-approval use of LNG-releasing IUSs. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
No drug-drug interaction studies have been conducted with LILETTA.
Contraceptive effect of LILETTA 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.
LILETTA is contraindicated for use in pregnant women because there is no need for pregnancy prevention in a woman who is already pregnant and LILETTA may cause adverse pregnancy outcomes. If a woman 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 woman. 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. Animal reproduction studies have not been conducted with LILETTA. Advise a woman of the potential risks if pregnancy occurs with LILETTA in place.
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. 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 another LNG-releasing IUS. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LILETTA and any potential adverse effects on the breastfed child from LILETTA or from the underlying maternal condition.
Safety and efficacy of LILETTA have been established in females of reproductive age. Efficacy is expected to be the same for postpubertal females under the age of 16 as for users 16 years and older. Use of this product before menarche is not indicated [see Clinical Pharmacology (12.3)].
LILETTA has not been studied in women over age 65 and is not indicated for postmenopausal women.
No studies were conducted to evaluate the effect of hepatic disease on the disposition of LNG released from LILETTA [see Contraindications (4)].
No studies were conducted to evaluate the effect of renal disease on the disposition of LNG released from LILETTA.
The safety and efficacy of LILETTA have been evaluated in overweight, obese, and morbidly obese patients. There was no apparent effect of BMI or body weight on contraceptive efficacy [see Clinical Pharmacology (12.3)].
LILETTA (levonorgestrel-releasing intrauterine system) contains 52 mg of levonorgestrel, a progestin, and is intended to provide an initial release rate of 19.5 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, has a molecular weight of 312.45, a molecular formula of C21H28O2, and the following structural formula:
LILETTA consists of a T-shaped polyethylene frame (T-frame) with a drug reservoir around the vertical stem (Figure 14). 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 14: Diagram of LILETTA
The inserter device provided with LILETTA is a single-use, disposable, sterile insertion system (tube, flange, rod; Figure 15), partially preloaded with the IUS product for intrauterine administration.
Once LILETTA has been inserted, the inserter is discarded.
Figure 15: Diagram of Inserter
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.
LILETTA has mainly local progestogenic effects in the uterine cavity. High local concentrations of LNG lead to morphological changes including stromal pseudodecidualization, glandular atrophy, a leukocytic infiltration, and a decrease in glandular and stromal mitoses. Changes in the uterine endometrium may lead to alterations in the menstrual bleeding pattern [see Warnings and Precautions (5.8)].
In clinical trials with other LNG-releasing IUSs, ovulation was inhibited in some women but most cycles were ovulatory.
Low doses of LNG are administered into the uterine cavity with the LILETTA intrauterine delivery system. The initial in vivo release rate is 19.5 mcg/day and decreases to 17.0 mcg/day at 1 year, 14.8 mcg/day at 2 years, 12.9 mcg/day at 3 years and 11.3 at 4 years.
In the phase 3 study, systemic LNG concentrations were assessed in a subset of subjects through Month 30 and in all subjects at Month 36 and after. Plasma LNG concentrations following insertion of LILETTA are shown in Table 4.
(N = 40)
(N = 36)
(N = 33)
(N = 30)
(N = 787)
(N = 302)
|252 ± 123||195 ± 68||168 ± 51||150 ± 47||134 ± 55||134 ± 61|
The apparent volume of distribution of LNG at steady-state following oral administration is reported to be approximately 1.8 L/kg. It is about 98.9% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin.
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. LNG and its phase I metabolites are excreted primarily as glucuronide conjugates. 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. In vitro studies have demonstrated that oxidative metabolism of LNG is catalyzed by CYP enzymes, especially CYP3A4.
About 45% of LNG and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates. The elimination half-life of LNG after a single oral administration is approximately 13.9 ± 3.2 hours.
Pediatric: Safety and efficacy of LILETTA have been established in females of reproductive age. The LILETTA clinical trial included 11 subjects aged 16 to 17 years; no pregnancies occurred in these subjects through 4 years of use of LILETTA.
Race: The effect of race on plasma LNG concentrations after LILETTA insertion was assessed in 629 (80%) White subjects, 94 (12%) Black subjects, 34 (4%) Asian subjects, 8 (1%) American Indian/Alaska Native subjects, 17 (2%) multiple-race subjects. Race does not appear to affect LNG concentrations following LILETTA insertion.
Obesity: The LILETTA clinical trial included overweight (24%), obese (24%), and morbidly obese (5%) women. LNG systemic exposure decreased with increasing body weight; however, there was no apparent effect of body mass index (BMI) or body weight on contraceptive efficacy.
[See Warnings and Precautions (5.9).]
LILETTA was studied in a multicenter, randomized, open-label clinical trial conducted in the US that enrolled 1,910 generally healthy women aged 16 to 45 years, 1,751 of whom received LILETTA. LILETTA was inserted in 1,011 (58%) nulliparous and 740 (42%) parous women. Women with a history of ectopic pregnancy, PID, or trophoblastic disease without a subsequent intrauterine pregnancy, who were less than 4 weeks post-pregnancy, had HIV, or were not in a mutually monogamous relationship at study entry were excluded. The demographics of enrolled women who received LILETTA were: Caucasian 78.4%, Black or African American 13.3%, Asian 3.9%, American Indian or Alaska Native 1.2%, Native Hawaiian or Other Pacific Islander 0.3%; 2.9% identified multiple races; 14.7% indicated Hispanic ethnicity. The clinical trial had no upper or lower weight or BMI limit and the BMI range was 15.8 – 61.6 kg/m2. The mean BMI of LILETTA subjects was 26.9 kg/m2; 24% were overweight, 24% were obese (BMI ≥ 30 kg/m2), and 5% were morbidly obese (BMI ≥ 40 kg/m2).
The pregnancy rate calculated as the Pearl Index (PI) in women aged 16 to 35 years, inclusive, 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 two pregnancies and the cumulative 4-year pregnancy rate was calculated by the life table method, based on a total of eight pregnancies that occurred after the onset of treatment and within 7 days after LILETTA removal or expulsion. Contraceptive protection did not appear to vary by parity, race or body mass index. Table 5 shows the annual PI for each of the four years and the calculated cumulative life table pregnancy rates through years 1, 2, 3 and 4.
|LILETTA Clinical Trial||Number of 28-Day Cycles of Exposure
Pregnancy Rate (95% CI)
|Cumulative 28-Day Cycles of Exposure||Cumulative Year
|Year 1||17,175||0.15 (0.02, 0.55)||17,175||0.14 (0.04, 0.57)|
|Year 2||14,205||0.37 (0.10, 0.94)||31,380||0.49 (0.22, 1.09)|
|Year 3||11,760||0.11 (0.00, 0.62)||43,140||0.59 (0.28, 1.25)|
|Year 4||9,755||0.13 (0.00, 0.74)||52,895||0.73 (0.36, 1.47)|
The use of LILETTA does not appear to alter the course of female fertility after removal of the IUS. Of 153 women who desired pregnancy after study discontinuation, 78% conceived within 6 months following LILETTA removal, and 88% conceived within 12 months after removal of LILETTA.
(1) Workowski KA, Berman S; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17;59(RR-12):1-110.
LILETTA (levonorgestrel-releasing intrauterine system), containing 52 mg levonorgestrel, is packaged together with an inserter in a peelable pouch, and is available in a carton of one sterile unit. NDC # 52544-035-54.
LILETTA is supplied sterile. LILETTA is sterilized with ethylene oxide. Do not resterilize. For single use only. Do not use if the inner pouch is damaged or opened. Insert before the end of the month shown on the pouch. Store at 20 – 25°C (68 – 77°F), with excursions permitted between 15 – 30°C (59 – 86°F) [See USP Controlled Room Temperature]. Store pouch in outer carton until use to protect from light.
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Complete the Follow-Up Reminder Card and give it to the patient.
LILETTA® and its design are registered trademarks of Odyssea Pharma SPRL, an Allergan affiliate.
Odyssea Pharma, Belgium
An affiliated company of Allergan USA, Inc.
Allergan USA, Inc. Irvine, CA 92612
Allergan USA, Inc. Medicines360
Irvine, CA 92612 San Francisco, CA 94111
© 2017 Allergan and Medicines360. All rights reserved.
(levonorgestrel-releasing intrauterine system)
LILETTA does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs).
Read this Patient Information carefully before you decide if LILETTA 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 LILETTA, ask your healthcare provider. You should also learn about other birth control methods to choose the one that is best for you.
What is LILETTA?
LILETTA 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 LILETTA releases LNG into your uterus, only small amounts of the hormone enter your blood. LILETTA does not contain estrogen.
Two thin threads are attached to the stem (lower end) of LILETTA. The threads are the only part of LILETTA you can feel when LILETTA is in your uterus; however, unlike a tampon string, the threads do not extend outside your body.
What if I need birth control for more than 4 years?
LILETTA must be removed after 4 years. Your healthcare provider can place a new LILETTA during the same office visit if you choose to continue using LILETTA.
What if I want to stop using LILETTA?
LILETTA is intended for use up to 4 years, but you can stop using LILETTA at any time by asking your healthcare provider to remove it. You could become pregnant as soon as LILETTA 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 LILETTA is removed to prevent pregnancy.
What if I change my mind about birth control and want to become pregnant in less than 4 years?
Your healthcare provider can remove LILETTA at any time. You could become pregnant as soon as LILETTA is removed. About 6 out of 7 women who want to become pregnant will become pregnant sometime in the first year after LILETTA is removed.
How does LILETTA work? LILETTA 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 LILETTA 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.
LILETTA, an intrauterine system (IUS), is in the box at the top of the chart.
Who might use LILETTA?
You might choose LILETTA if you:
Do not use LILETTA if you:
Before having LILETTA placed, tell your healthcare provider if you have any medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How is LILETTA placed?
LILETTA is placed by your healthcare provider during an in-office visit.
First, your healthcare provider will examine your pelvis to find the exact position of your uterus. Your healthcare provider will then clean your vagina and cervix with an antiseptic solution and slide a slim plastic tube containing LILETTA through the cervix into your uterus. Your healthcare provider will then remove the plastic tube, and leave LILETTA in your uterus. Your healthcare provider will trim the threads to the right length. Placement takes only a few minutes.
You may experience pain, bleeding, or dizziness during and after placement. If your symptoms do not pass within 30 minutes after placement, LILETTA may not have been placed correctly. Your healthcare provider will examine you to see if LILETTA needs to be removed or replaced.
Should I check that LILETTA is in place?
Yes, you should check that LILETTA is in proper position by feeling the threads. It is a good habit to do this 1 time a month. Your healthcare provider should teach you how to check that LILETTA is in place. First, wash your hands with soap and water. You can check by reaching up to the top of your vagina with clean fingers to feel the threads. Do not pull on the threads.
If you feel more than just the threads or if you cannot feel the threads, LILETTA may not be in the right position and may not prevent pregnancy. Use non-hormonal back-up birth control (such as condoms and spermicide) and ask your healthcare provider to check that LILETTA is still in the right place.
How soon after placement of LILETTA should I return to my healthcare provider?
Call your healthcare provider if you have any questions or concerns (see “When should I call my healthcare provider?”). Otherwise, you should return to your healthcare provider for a follow-up visit 4 to 6 weeks after LILETTA is placed to make sure that LILETTA is in the right position.
Can I use tampons with LILETTA?
Yes, tampons may be used with LILETTA.
What if I become pregnant while using LILETTA?
Call your healthcare provider right away if you think you are pregnant. If possible, also do a urine pregnancy test. If you get pregnant while using LILETTA, you may have an ectopic pregnancy. This means that the pregnancy is not in the uterus. Unusual vaginal bleeding or abdominal pain especially with missed periods may be a sign of ectopic pregnancy.
Ectopic pregnancy is a medical emergency that often requires surgery. Ectopic pregnancy can cause internal bleeding, infertility, and even death. There are also risks if you get pregnant while using LILETTA and the pregnancy is in the uterus. Severe infection, miscarriage, premature labor, premature delivery, and even death can occur with pregnancies that continue with an intrauterine system (IUS). Because of this, your healthcare provider may try to remove LILETTA, even though removing it may cause a miscarriage. If LILETTA cannot be removed, talk with your healthcare provider about the benefits and risks of continuing the pregnancy.
If you continue your pregnancy, see your healthcare provider regularly. Call your healthcare provider right away if you get flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge, or fluid leaking from your vagina. These may be signs of infection.
It is not known if LILETTA can cause long-term effects on the fetus if it stays in place during a pregnancy.
How will LILETTA change my periods?
For the first 3 to 6 months, your period may become irregular and the number of bleeding days may increase. You may also have frequent spotting or light bleeding and cramping. Some women have heavy bleeding during this time. After you have used LILETTA for a while, the number of bleeding and spotting days is likely to lessen. For some women, menstrual periods will stop altogether. When LILETTA is removed, your menstrual periods will likely return to their former pattern.
Is it safe to breastfeed while using LILETTA?
You may use LILETTA when you are breastfeeding if more than 6 weeks have passed since you had your baby. If you are breastfeeding, LILETTA is not likely to affect the quality or amount of your breast milk or the health of your nursing baby. However, isolated cases of decreased milk production have been reported among women using progestin-only birth control pills. The risk of LILETTA becoming attached to (embedded) or going through the wall of the uterus is increased when LILETTA is placed in breastfeeding women.
Will LILETTA interfere with sexual intercourse?
You and your partner should not feel LILETTA during intercourse. LILETTA is placed in the uterus, not in the vagina. In some cases, your partner may feel the threads. If this occurs, or if you or your partner experience pain during sex, talk with your healthcare provider.
Can I have an MRI with LILETTA in place?
LILETTA is MR Safe. It is safe to have an MRI following LILETTA placement.
What are the possible side effects of LILETTA?
LILETTA can cause serious side effects, including:
Tell your healthcare provider right away if you have any of these signs of PID or endometritis: long-lasting or heavy bleeding, unusual vaginal discharge, low abdominal pain, painful sex, chills, or fever.
The most common side effects of LILETTA include:
These are not all the possible side effects of LILETTA. For more information, ask your healthcare provider or pharmacist.
Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to Allergan at 1-800-678-1605.
After LILETTA has been inserted, when should I call my healthcare provider?
Call your healthcare provider if you have any concerns about LILETTA. Be sure to call if you:
General information about the safe and effective use of LILETTA.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.
You can ask your pharmacist or healthcare provider for information about LILETTA that is written for health professionals.
For more information, go to www.LILETTA.com or call 1-855-LILETTA (1-855-545-3882).
This Patient Information has been approved by the U.S. Food and Drug Administration.
LILETTA® and its design are registered trademarks of Odyssea Pharma SPRL, an Allergan affiliate.
Odyssea Pharma, Belgium
An affiliated company of Allergan USA, Inc.
Allergan USA, Inc. Irvine, CA 92612
Allergan USA, Inc. Medicines360
Irvine, CA 92612 San Francisco, CA 94111
© 2017 Allergan and Medicines360. All rights reserved.
Approved: October 2017
levonorgestrel intrauterine device
|Labeler - Actavis Pharma, Inc. (119723554)|