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: 11.1 Kyleena 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 . The components of Kyleena, including its packaging, are not manufactured using natural rubber latex. Figure 10. Kyleena Kyleena 11.2 Inserter 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

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.

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

• 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. • To be inserted by a trained healthcare provider using strict aseptic technique. Follow insertion instructions exactly as described. • Patient should be re-examined and evaluated 4 to 6 weeks after insertion; then yearly or more often if clinically indicated

Dosing 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 . 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 . Do not open the package until required for insertion . Do not use if the seal of the sterile package is broken or appears compromised. Use strict aseptic techniques throughout the insertion procedure . 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. 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 . • 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 . • 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 that method for 7 days after Kyleena insertion or until the end of the current treatment cycle. • If the woman was using continuous hormonal contraception, discontinue that method seven days after Kyleena insertion. Switching to Kyleena from an injectable progestin contraceptive • Insert Kyleena at any time; a non-hormonal back-up birth control (such as condoms or spermicide) should also be used for 7 days if Kyleena is inserted more than 3 months (13 weeks) after the last injection. Switching to Kyleena from a contraceptive implant or another IUS • Insert Kyleena on the same day the implant or IUS is removed. • Insert Kyleena at any time during the menstrual cycle. Inserting Kyleena after first trimester abortion or miscarriage • Insert Kyleena immediately after a first-trimester abortion or miscarriage, unless it is a septic abortion . Inserting Kyleena after childbirth or second-trimester abortion or miscarriage • Immediate insertion after childbirth or second-trimester abortion or miscarriage • Insert Kyleena after removal of the placenta. Back-up contraception is not needed. . Interval insertion following complete involution of the uterus • Wait a minimum of 6 weeks or until the uterus is fully involuted before inserting Kyleena . • Insert Kyleena any time there is reasonable certainty the woman is not pregnant. • If Kyleena is not inserted during the first 7 days of the menstrual cycle, a back-up method of contraception should be used, or the woman should abstain from vaginal intercourse for 7 days to prevent pregnancy . Tools for Insertion Note: The inserter provided with Kyleena and the Insertion Procedure described in this section are not applicable for immediate insertion after childbirth or second-trimester abortion or miscarriage. For immediate insertion, remove Kyleena from the inserter by first loading and then releasing Kyleena from the inserter, and insert according to accepted practice. Preparation • Gloves • Speculum • Sterile uterine sound • Sterile tenaculum • Antiseptic solution, applicator Procedure • Sterile gloves • Kyleena with inserter in sealed package • Instruments and anesthesia for paracervical block, if anticipated • Consider having an unopened back-up Kyleena available • Sterile, sharp curved scissors Preparation for insertion • Exclude pregnancy and confirm that there are no other contraindications to the use of Kyleena. • With the patient comfortably in lithotomy position, do a bimanual exam to establish the size, shape and position of the uterus. • Gently insert a speculum to visualize the cervix. • Thoroughly cleanse the cervix and vagina with a suitable antiseptic solution. • Prepare to sound the uterine cavity. Grasp the upper lip of the cervix with a tenaculum forceps and gently apply traction to stabilize and align the cervical canal with the uterine cavity. Perform a paracervical block if needed. If the uterus is retroverted, it may be more appropriate to grasp the lower lip of the cervix. The tenaculum should remain in position and gentle traction on the cervix should be maintained throughout the insertion procedure. • Gently insert a uterine sound to check the patency of the cervix, measure the depth of the uterine cavity in centimeters, confirm cavity direction, and detect the presence of any uterine anomaly. If you encounter difficulty or cervical stenosis, use dilatation, and not force, to overcome resistance. If cervical dilatation is required, consider using a paracervical block. Insertion Procedure Proceed with insertion only after completing the above steps and ascertaining that the patient is appropriate for Kyleena. Ensure use of aseptic technique throughout the entire procedure . Step 1–Opening of the package • Open the package (Figure 1). The contents of the package are sterile. Figure 1. Opening the Kyleena Package • Using sterile gloves, lift the handle of the sterile inserter and remove from the sterile package. Package Step 2–Load Kyleena into the insertion tube • Push the slider forward as far as possible in the direction of the arrow, thereby moving the insertion tube over the Kyleena T-body to load Kyleena into the insertion tube (Figure 2). The tips of the arms will meet to form a rounded end that extends slightly beyond the insertion tube. Figure 2. Move slider all the way to the forward position to load Kyleena • Maintain forward pressure with your thumb or forefinger on the slider . DO NOT move the slider downward at this time as this may prematurely release the threads of Kyleena. Once the slider is moved below the mark, Kyleena cannot be re-loaded . Load Kyleena Step 3–Setting the Flange • Holding the slider in this forward position, set the upper edge of the flange to correspond to the uterine depth (in centimeters) measured during sounding (Figure 3). Figure 3. Setting the flange Setting Flange Step 4–Kyleena is now ready to be inserted • Continue holding the slider in this forward position. Advance the inserter through the cervix until the flange is approximately 1.5–2 cm from the cervix and then pause (Figure 4). Figure 4. Advancing insertion tube until flange is 1.5 to 2 cm from the cervix Do not force the inserter. If necessary, dilate the cervical canal. Advancing Flange Step 5–Open the arms • While holding the inserter steady, move the slider down to the mark to release the arms of Kyleena (Figure 5). Wait 10 seconds for the horizontal arms to open completely. Figure 5. Move the slider back to the mark to release and open the arms Back to Mark Step 6–Advance to fundal position Advance the inserter gently towards the fundus of the uterus until the flange touches the cervix . If you encounter fundal resistance do not continue to advance. Kyleena is now in the fundal position (Figure 6). Fundal positioning of Kyleena is important to prevent expulsion . Figure 6. Move Kyleena into the fundal position Funda Position Step 7–Release Kyleena and withdraw the inserter • Holding the entire inserter firmly in place, release Kyleena by moving the slider all the way down (Figure 7). Figure 7. Move the slider all the way down to release Kyleena from the insertion tube • Continue to hold the slider all the way down while you slowly and gently withdraw the inserter from the uterus. • Using a sharp, curved scissor, cut the threads perpendicular, leaving about 3 cm visible outside of the cervix [cutting threads at an angle may leave sharp ends (Figure 8)]. Do not apply tension or pull on the threads when cutting to prevent displacing Kyleena. Figure 8. Cutting the threads Kyleena insertion is now complete. Prescribe analgesics, if indicated. Record the Kyleena lot number in the patient records. Moving Slider Cutting Threads Important information to consider during or after insertion • If you suspect that Kyleena is not in the correct position, check placement (for example, using transvaginal ultrasound). Remove Kyleena if it is not positioned completely within the uterus. Do not reinsert a removed Kyleena. • If there is clinical concern, exceptional pain or bleeding during or after insertion, take appropriate steps (such as physical examination and ultrasound) immediately to exclude perforation

Patient Follow-up • Reexamine and evaluate patients 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated

Removal of Kyleena Timing of Removal • Kyleena should not remain in the uterus after 5 years. • If pregnancy is not desired, remove Kyleena during the first 7 days of the menstrual cycle, provided the woman is still experiencing regular menses. If removal will occur at other times during the cycle or the woman does not experience regular menses, she is at risk of pregnancy; start a new contraceptive method a week prior to removal for these women. Tools for Removal Preparation • Gloves • Speculum Procedure • Sterile forceps Removal Procedure • Remove Kyleena by applying gentle traction on the threads with forceps (Figure 9). Figure 9. Removal of Kyleena • If the threads are not visible, determine location of Kyleena by ultrasound . • If Kyleena is found to be in the uterine cavity on ultrasound exam, it may be removed using a narrow forceps, such as an alligator forceps. This may require dilation of the cervical canal. After removal of Kyleena, examine the system to ensure that it is intact. • If unable to remove with gentle traction, determine Kyleena location and exclude perforation by ultrasound or other imaging . • Removal may be associated with some: o pain and/or bleeding or vasovagal reactions (for example, syncope, bradycardia) or seizure, especially in patients with a predisposition to these conditions. o breakage or embedment of Kyleena in the myometrium that can make removal difficult . Analgesia, paracervical anesthesia, cervical dilation, alligator forceps or other grasping instrument, or hysteroscopy may be used to assist in removal. Removal 2.5 Continuation of Contraception after Removal • If pregnancy is not desired and if a woman wishes to continue using Kyleena, a new system can be inserted immediately after removal any time during the cycle. • If a patient with regular cycles wants to start a different contraceptive method, time removal and initiation of the new method to ensure continuous contraception. Either remove Kyleena during the first 7 days of the menstrual cycle and start the new method immediately thereafter or start the new method at least 7 days prior to removing Kyleena if removal is to occur at other times during the cycle. • If a patient with irregular cycles or amenorrhea wants to start a different contraceptive method, start the new method at least 7 days before removal.

• 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. • Group A streptococcal infection has been reported following insertion of LNG IUS; strict aseptic technique is essential during insertion. • Before using Kyleena, consider the risks of PID. • 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. • Partial or complete expulsion may occur, which can be unnoticed, leading to loss of contraceptive efficacy. • Evaluate persistent enlarged ovarian follicles or ovarian cysts. • Bleeding patterns become altered, may remain irregular and amenorrhea may ensue. • Kyleena can be safely scanned with MRI only under certain conditions. 5.1 Risk 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

Risks 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 . Follow her pregnancy closely and advise her to report immediately any symptom that suggests complications of the pregnancy

Sepsis 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

Pelvic 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 suspected PID or in women with a history of PID unless there has been a subsequent intrauterine pregnancy . IUDs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. In clinical trials, PID was observed in 0.5% of women overall and occurred more frequently within the first year and most often within the first month after insertion of Kyleena. Women at increased risk for PID PID is often associated with a sexually transmitted infection (STI), and Kyleena does not protect against STI. The risk of PID 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 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], intravenous drug abuse). Subclinical PID PID may be asymptomatic but still result in tubal damage and its sequelae. Treatment of PID Following a diagnosis of PID, or suspected PID, bacteriologic specimens should be obtained, and antibiotic therapy should be initiated promptly. Removal of Kyleena after initiation of antibiotic therapy is usually appropriate. 1 Actinomycosis Actinomycosis has been associated with IUDs. Remove Kyleena from symptomatic women and treat with antibiotics. The significance of actinomyces-like organisms on Pap smear in an asymptomatic IUD user is unknown, and so this finding alone does not always require Kyleena removal and treatment. When possible, confirm a Pap smear diagnosis with cultures

Perforation Perforation (total or partial, including penetration/embedment of Kyleena in the uterine wall or cervix) may occur most often during insertion, although the perforation may not be detected until sometime later. The incidence of perforation during clinical trials was < 0.1%. The risk of uterine perforation is increased in women who have recently given birth, and in women who are breastfeeding at the time of insertion. In a large postmarketing safety study conducted in the US, the risk of uterine perforation was highest when insertion occurred within ≤ 6 weeks postpartum, and also higher with breastfeeding at the time of insertion . The risk of perforation may be increased if Kyleena is inserted when the uterus is fixed, retroverted or not completely involuted. If perforation occurs, locate and remove Kyleena. Surgery may be required. Delayed detection or removal of Kyleena in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses and erosion of adjacent viscera. In addition, perforation may reduce contraceptive efficacy and result in pregnancy

Expulsion Partial or complete expulsion of Kyleena may occur resulting in the loss of efficacy. Expulsion may be associated with symptoms of bleeding or pain, or it may be asymptomatic and go unnoticed. Kyleena typically decreases menstrual bleeding over time; therefore, an increase of menstrual bleeding may be indicative of an expulsion. Consider further diagnostic imaging, such as x-ray, if expulsion is suspected based on ultrasound . In clinical trials, a 5-year expulsion rate of 3.5% (59 out of 1,690 subjects) was reported. The risk of expulsion is increased with insertions immediately after delivery and appears to be increased with insertion after second-trimester abortion based on limited data. In a large postmarketing safety study conducted in the US, the risk of expulsion was lower with breastfeeding status . Remove a partially expelled Kyleena. If expulsion has occurred, a new Kyleena can be inserted any time the provider can be reasonably certain the woman is not pregnant

Ovarian Cysts Because the contraceptive effect of Kyleena is mainly due to its local effects within the uterus, ovulatory cycles with follicular rupture usually occur in women of fertile age using Kyleena. Ovarian cysts (reported as adverse reactions if they were abnormal, non-functional cysts and/or had a diameter >3 cm on ultrasound examination) were reported at least once over the course of clinical trials in 22% of women using Kyleena, and 0.6% of subjects discontinued because of an ovarian cyst. Most ovarian cysts are asymptomatic, although some may be accompanied by pelvic pain or dyspareunia. In most cases the ovarian cysts disappear spontaneously during two to three months observation. Evaluate persistent ovarian cysts. Surgical intervention is not usually required

Bleeding Pattern Alterations Kyleena can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea and amenorrhea. During the first 3–6 months of Kyleena use, the number of bleeding and spotting days may be higher and bleeding patterns may be irregular. Thereafter, the number of bleeding and spotting days usually decreases but bleeding may remain irregular. In Kyleena clinical trials, amenorrhea developed by the end of the first year of use in approximately 12% of Kyleena users. A total of 81 subjects out of 1,697 (4.8%) discontinued due to uterine bleeding complaints. Table 2 shows the bleeding patterns as documented in the Kyleena clinical trials based on 90-day reference periods. Table 3 shows the number of bleeding and spotting days based on 28-day cycle equivalents. Table 2: Bleeding Patterns Reported with Kyleena in Contraception Studies (by 90-day reference periods) Kyleena First 90 days N=1,566 Second 90 days N=1,511 End of year 1 N=1,371 End of year 3 N=975 End of year 5 N=530 Amenorrhea 1 <1% 5% 12% 20% 23% Infrequent bleeding 2 10% 20% 26% 26% 26% Frequent bleeding 3 25% 10% 4% 2% 2% Prolonged bleeding 4 57% 14% 6% 2% 1% Irregular bleeding 5 43% 25% 17% 10% 9% 1 Defined as subjects with no bleeding/spotting throughout the 90-day reference period 2 Defined as subjects with 1 or 2 bleeding/spotting episodes in the 90-day reference period 3 Defined as subjects with more than 5 bleeding/spotting episodes in the 90-day reference period 4 Defined as subjects with bleeding/spotting episodes lasting more than 14 days in the 90-day reference period. Subjects with prolonged bleeding may also be included in one of the other categories (excluding amenorrhea) 5 Defined as subjects with 3 to 5 bleeding/spotting episodes and less than 3 bleeding/spotting-free intervals of 14 or more days Table 3: Mean number of Bleeding and Spotting Days per 28-day Cycle Equivalent 28-day Cycle Equivalent Cycle 1 N=1,619 Cycle 4 N=1,575 Cycle 7 N=1,518 Cycle 13 N=1,394 Cycle 39 N=913 Cycle 65 N=322 Days on treatment 1–28 85–112 169–196 337–364 1065–1092 1793-1820 Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Number of bleeding days 7.2 3.2 2.2 1.5 1.0 0.9 Number of spotting days 8.6 4.6 3.5 2.9 2.2 2.1 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

Breast Cancer Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception, including Kyleena, because some breast cancers are hormone-sensitive . Spontaneous reports of breast cancer have been received during postmarketing experience with a LNG-releasing IUS. Observational studies of the risk of breast cancer with use of a LNG-releasing IUS do not provide conclusive evidence of increased risk

Clinical Considerations for Use and Removal Use Kyleena with caution after careful assessment if any of the following conditions exist, and consider removal of the system if any of them arise during use: • Coagulopathy or use of anticoagulants • Migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia • Exceptionally severe headache • Marked increase of blood pressure • Severe arterial disease such as stroke or myocardial infarction In addition, consider removing Kyleena if any of the following conditions arise during use: • Uterine or cervical malignancy • Jaundice 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 system may have been displaced (for example, expelled or perforated the uterus) . Exclude pregnancy and verify the location of Kyleena, for example, by sonography, X-ray, or by gentle exploration of the cervical canal with a suitable instrument. If Kyleena is displaced, remove it. A new Kyleena may be inserted at that time or during the next menses if it is certain that conception has not occurred. If Kyleena is in place with no evidence of perforation, no intervention is indicated

Magnetic Resonance Imaging (MRI) Safety Information Non-clinical testing has demonstrated that Kyleena is MR Conditional. A patient with Kyleena can be safely scanned in an MR system meeting the following conditions: • Static magnetic field of 3.0 T or less • Maximum spatial field gradient of 36,000 gauss/cm (360 T/m) • Maximum MR system reported, whole body averaged specific absorption rate (SAR) of 4W/kg (First Level Controlled Operating Mode) Under the scan conditions defined above, the Kyleena IUS is expected to produce a maximum temperature rise of less than 2°C after 15 minutes of continuous scanning. In non-clinical testing, the image artifact caused by the IUS extended up to 5 mm from the IUS when imaged with a gradient echo pulse sequence and a 3.0 T MRI system. MRI

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.