Liletta

The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling:

• Ectopic Pregnancy [see WARNINGS AND PRECAUTIONS]
• Intrauterine Pregnancy [see WARNINGS AND PRECAUTIONS]
• Group A Streptococcal Sepsis (GAS) [see WARNINGS AND PRECAUTIONS]
• Pelvic Inflammatory Disease or Endometritis [see WARNINGS AND PRECAUTIONS]
• Perforation [see WARNINGS AND PRECAUTIONS]
• Expulsion [see WARNINGS AND PRECAUTIONS]
• Ovarian Cysts [see WARNINGS AND PRECAUTIONS]
• Bleeding Pattern Alterations [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

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 1,412 exposed for 1 year and 383 subjects who completed 3 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, and 5.3% had a BMI ≥ 40 kg/m². The data cover more than 22,000 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% users) are shown in Table 3.

Table 3: Adverse Reactions in ≥ 5% of LILETTA Users in Phase 3 Clinical Study

In the contraceptive trial, 12.3% of LILETTA users discontinued prematurely due to an adverse reaction. The most common adverse reaction leading to discontinuation was expulsion (3.5%), bleeding complaints (a total of 1.5%). The next most common adverse reactions causing discontinuation were acne (1.3%), mood swings (1.3%), dysmenorrhea (0.6%), and uterine spasm (0.6%). Two women discontinued the clinical study due to PID and one due to endometritis.

In the clinical trial, serious adverse reactions included: suicidality and exacerbations of depression and bipolar disorder, ectopic pregnancy, ovarian cysts, and IUS perforation requiring a laparoscopic surgery.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of other 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.

• Hypersensitivity including rash, urticaria, and angioedema
• Device Breakage

LILETTA
(lye-LET-uh)
(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 hormone-releasing system inserted in your uterus by your healthcare provider to prevent pregnancy for up to 3 years.
• LILETTA can be removed by your healthcare provider at any time.
• LILETTA can be used whether or not you have given birth to a child.

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 should 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 3 years?

LILETTA must be removed after 3 years. Your healthcare provider can insert 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 3 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. Discuss your options with your healthcare provider, because certain methods should be started 7 days before LILETTA is removed to ensure continued birth control.

What if I change my mind about birth control and want to become pregnant in less than 3 years?

Your healthcare provider can remove LILETTA at any time. You could become pregnant as soon as LILETTA is removed. About 5 out of 6 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 by 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:

• want birth control that provides a low chance of getting pregnant (less than 1 in 100)
• want birth control that works continuously for up to a maximum of 3 years
• want birth control that is reversible
• want a birth control method that you do not need to take daily
• are willing to use a birth control method that is inserted in the uterus
• want birth control that does not contain estrogen

Who should not use LILETTA?

Do not use LILETTA if you:

• are or might be pregnant; LILETTA cannot be used as an emergency contraceptive
• have had a serious pelvic infection called pelvic inflammatory disease (PID) unless you have had a normal pregnancy after the infection went away
• have an untreated pelvic infection now
• have had a serious pelvic infection in the past 3 months after a pregnancy
• can get infections easily. For example, if you:
  • have problems with your immune system
  • have multiple sexual partners or your partner has multiple sexual partners
  • use or abuse intravenous drugs
• have or suspect you might have cancer of the uterus or cervix
• have bleeding from the vagina that has not been explained
• have liver disease or liver tumor
• have breast cancer or any other cancer that is sensitive to progestin (a female hormone), now or in the past
• have an intrauterine system in your uterus already
• have a condition of the uterus that changes the shape of the uterine cavity, such as large fibroid tumors
• are allergic to levonorgestrel, silicone, polyethylene, or barium sulfate

Before having LILETTA inserted, tell your healthcare provider if you:

• have had a heart attack
• have had a stroke
• were born with heart disease or have problems with your heart valves
• have problems with blood clotting or take medicine to reduce clotting
• have high blood pressure
• recently had a baby or if you are breastfeeding
• have severe migraine headaches
• are or might be pregnant
• have acute pelvic inflammatory disease or a history of pelvic inflammatory disease
• have AIDS, HIV, or any other sexually transmitted infection
• have any other medical conditions

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How is LILETTA inserted?

LILETTA is inserted 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 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. insertion takes only a few minutes.

You may experience pain, bleeding, or dizziness during and after insertion. If your symptoms do not pass within 30 minutes after insertion, LILETTA may not have been inserted 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.

If LILETTA is accidentally removed and you had vaginal intercourse within the preceding24 hours, you may be at risk of pregnancy, and should talk to a healthcare provider.

How soon after insertion 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 inserted to make sure that LILETTA is in the right position.

Can I use tampons with LILETTA?

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 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 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 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. 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.

if you have any concerns that you may be pregnant while using LILETTA, do a urine pregnancy test or call your healthcare provider.

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.

Will LILETTA interfere with sexual intercourse?

You and your partner should not feel LILETTA during intercourse. LILETTA is inserted 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 insertion.

What are the possible side effects of LILETTA?

LILETTA can cause serious side effects, including:

• ectopic pregnancy. If you get pregnant while using LILETTA, you might have an ectopic pregnancy. This means that the pregnancy is not in the uterus. Unusual vaginal bleeding or abdominal pain 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.
• intrauterine pregnancy risks. There are also risks if you get pregnant while using LILETTA and the pregnancy is in the uterus. Severe infection, miscarriage, 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, after seeing your healthcare provider, you choose to 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.
• life-threatening infection. Life-threatening infection can occur within the first few days after LILETTA is inserted. Call your healthcare provider immediately if you develop severe pain or fever shortly after LILETTA is inserted.
• pelvic inflammatory disease (PID). Some IUS users get a serious pelvic infection called pelvic inflammatory disease (PID). PID is usually sexually transmitted. You have a higher chance of getting PID if you or your partner has sex with other partners. PID can cause serious problems such as infertility, ectopic pregnancy or pelvic pain that does not go away. PID is usually treated with antibiotics. More serious cases of PID may require surgery. Removal of the uterus (hysterectomy) is sometimes needed. in rare cases, infections that start as PID can even cause death.
  Tell your healthcare provider right away if you have any of these signs of PID: long-lasting or heavy bleeding, unusual vaginal discharge, low abdominal pain, painful sex, chills, or fever.
• perforation. LILETTA may become attached to (embedded) or go through the wall of the uterus. This is called perforation (or embedment). if this occurs, LILETTA may no longer prevent pregnancy. If perforation occurs, LILETTA may move outside the uterus and can cause internal scarring, infection, or damage to other organs. You may need surgery to have LILETTA removed if perforation or embedment occurs. The risk of perforation is increased in breastfeeding women.
• expulsion. LILETTA may come out of your uterus. This is called expulsion. Expulsion occurs in about 3 out of 100 women. You may become pregnant if LILETTA comes out. if you think that LILETTA has come out, use another birth control method like condoms and spermicide or do not have sex (vaginal intercourse) until you are seen by a healthcare provider.

The most common side effects of LILETTA include:

• vaginal infection
• infection of the outer part of your vagina (vulvovaginal)
• acne
• headache
• nausea/vomiting
• pain during sex
• abdominal pain
• breast pain
• pelvic pain
• depression
• mood changes
• Pain, bleeding, or dizziness during and after insertion. If these symptoms do not stop within 30 minutes after insertion, LILETTA may not have been inserted correctly. Your healthcare provider will examine you to see if LILETTA needs to be removed or replaced.
• Missed menstrual periods. About 1 out of 5 women stop having periods after 1 year of LILETTA use. If you have any concerns that you may be pregnant while using LILETTA, do a urine pregnancy test or call your healthcare provider. When LILETTA is removed, your menstrual periods will usually return to your previous pattern.
• Changes in bleeding. You may have bleeding and spotting between menstrual periods, especially during the first 3 to 6 months. Sometimes the bleeding is heavier than usual at first. However, the bleeding usually becomes lighter than usual and may be irregular. Call your healthcare provider if the bleeding remains heavier than usual or increases after it has been light for a while.
• Cysts on the ovary. Some women using LILETTA develop a painful cyst on the ovary. These cysts usually disappear on their own in 2 to 3 months. However, a cyst can cause pain and sometimes cysts will need surgery.

This is not a complete list of possible side effects with LILETTA. For more information, ask your healthcare provider. Tell your healthcare provider if you have any side effect that bothers you or does not go away.

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 Actavis at (800) 272-5525.

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:

• think you are pregnant
• have pelvic pain or pain during sex
• have unusual vaginal discharge or genital sores
• have unexplained fever, flu-like symptoms or chills
• might be exposed to sexually transmitted infections (STIS)
• are concerned that the IUS may have been expelled (came out)
• cannot feel LILETTA'S threads
• develop very severe or migraine headaches
• have yellowing of the skin or whites of the eyes. These may be signs of liver problems.
• have had a stroke or heart attack
• you or your partner becomes HIV positive
• have severe vaginal bleeding or bleeding that concerns 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.

This leaflet summarizes the most important information about LILETTA. if you would like more information, talk to your healthcare provider. 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 is a prescription medication that is a hormone-releasing system placed in the uterus to prevent pregnancy for up to 4 years.

Liletta belongs to a group of drugs called progestins which change the lining of the uterus, alter cervical mucus, and make it difficult for sperm to enter the uterus.

This medication is available as an intrauterine system and is inserted by a healthcare professional. This hormone-releasing system is a type of intrauterine system also known as an intrauterine device (IUD).

Common side effects of Liletta include infections of the vagina and acne.

• Actavis Pharma, Inc.

Levonorgestrel intrauterine system is a T-shaped plastic device that is inserted through the vagina and placed into the uterus by a doctor. The device is usually inserted within 7 days after the start of a menstrual period.

You may feel pain or dizziness during insertion of the IUD. You may also have minor vaginal bleeding. Tell your doctor if you still have these symptoms longer than 30 minutes.

The levonorgestrel device should not interfere with sexual intercourse, wearing tampons, or using other vaginal medications.

After each menstrual period, make sure you can still feel the removal strings. Wash your hands with soap and water, and insert your clean fingers into the vagina. You should be able to feel the strings at the opening of your cervix. Call your doctor at once if you cannot feel the strings, or if you think the device has slipped lower in your uterus or out of your uterus. A sudden increase in menstrual flow may be a sign that the device has slipped out of place.

If you think the device is not properly in place, use a non-hormone method of birth control (condom, or diaphragm with spermicide) to prevent pregnancy until your doctor is able to replace the IUD.

Your doctor will need to see you within a few weeks after insertion of the device to make sure it is still in place correctly. You will also need regular annual pelvic exams and Pap smears.

You may have irregular periods during the first 3 to 6 months of use. Your flow may be lighter or heavier, and you may eventually stop having periods after several months. Call your doctor if you miss a period or think you might be pregnant.

If you need to have an MRI (magnetic resonance imaging), tell your caregivers ahead of time that you have an IUD in place.

Your device may be removed at any time you decide to stop using birth control. The Mirena or Kyleena intrauterine system must be removed at the end of the 5-year wearing time. The Skyla or Liletta device must be removed after 3 years. Your doctor can insert a new device at that time if you wish to continue using this form of birth control. Only your doctor should remove the IUD. Do not attempt to remove the device yourself.

If you wish to continue preventing pregnancy, you may need to start using another birth control method a week before your levonorgestrel intrauterine system is removed.

An overdose of levonorgestrel released from the intrauterine system is very unlikely to occur.

In the U.S.

• Kyleena
• Liletta
• Mirena
• Skyla

Available Dosage Forms:

• Insert, Extended Release

Therapeutic Class: Contraceptive, Local

Pharmacologic Class: Progestin

This section provides information on the proper use of a number of products that contain levonorgestrel. It may not be specific to Liletta. Please read with care.

Your doctor will give you this medicine in a hospital or clinic. The intrauterine device (IUD) is inserted into your uterus.

This medicine comes with a patient information insert. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Your doctor may want to do tests to make sure you do not have an infection before putting in an IUD. The IUD is usually inserted during your monthly period, immediately after a miscarriage or an abortion in the first trimester of your pregnancy, at least 6 weeks after a miscarriage or an abortion in the second trimester of your pregnancy, or at least 6 weeks after giving birth. Putting an IUD in during a monthly period also helps to make sure that you are not pregnant. You will also need to see your doctor within 4 to 6 weeks of having your IUD placed and then once a year. Use another form of birth control or refrain from having sex if the IUD is not inserted during the first 7 days of your menstrual cycle.

Levonorgestrel IUD has a string or "tail" which is made of plastic thread. About one or two inches of this string hangs into your vagina. You cannot see this string, and it will not cause problems when you have sex. Check your IUD string every few days during the first few months that you have your IUD. After that, check the string after each monthly period. You may not be protected against pregnancy if you cannot feel the string or if you feel the plastic. Do the following to check the placement of your IUD:

• Wash your hands with soap and warm water. Dry them with a clean towel.
• Bend your knees and squat low to the ground.
• Gently put your index (pointing) finger high inside your vagina. The cervix is at the top of the vagina and feels like the tip of your nose. Find the IUD string coming from your cervix. Never pull on the string. You should not be able to feel the firm plastic of the IUD itself.
• Wash your hands after you are finished checking your IUD.

You will need to have your levonorgestrel-releasing IUD replaced every 3 years for Liletta™ or Skyla™, or 5 years for Kyleena™ or Mirena®, or sooner if it comes out of your uterus unexpectedly.

If you are using Mirena® IUD and want to stop, your doctor can remove it at any time. However, you may become pregnant as soon as it is removed. Use another form of birth control (eg, condoms, spermicides) or have a new IUD inserted at the same day of removal to keep from getting pregnant.

2.1 Dosing Over Time

Liletta contains 52 mg of levonorgestrel (LNG). Initially, LNG is released at a rate of 19.5 mcg/day. This rate decreases progressively to approximately 17.0 mcg/day at 1 year, 14.8 mcg/day at 2 years, 12.9 mcg/day at 3 years and 11.3 mcg/day at 4 years after insertion. The average in vivo release rate of LNG is approximately 15.4 mcg/day over a period of 4 years. 

Liletta can be removed at any time but must be removed by the end of the fourth year. Liletta can be replaced at the time of removal with a new Liletta if continued contraceptive protection is desired.

2.2 Timing of Insertion

Refer to Table 1 for instructions on when to start use of Liletta.

2.3 Insertion Instructions

Liletta (Figure 1a) is provided in a tray, sealed with a peel-off lid and is inserted into the uterine cavity with the provided inserter (Figure 1b) [see Description (11)] 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 1a: Liletta Intrauterine Contraceptive System (IUS)

Figure 1b: Liletta IUS with Inserter

The Liletta IUS is packaged partially preloaded within the inserter. The threads are passed through the insertion tube, and exit through an opening in the handle at the cleft.

The handle of the inserter contains a BLUE slider and a GREEN slider. The sliders are labeled with the numbers 1 and 2, and the handle is labeled with the number 3 to assist with the insertion process (Figure 2).   Moving the sliders achieves the positions required to complete the insertion process.

Figure 2: Inserter Sliders

Insertion

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.

• Obtain a complete medical and social history to determine conditions that might influence the selection of Liletta for contraception. If indicated, perform a physical examination and appropriate tests for genital or sexually transmitted infections. [See Contraindications (4) and Warnings and Precautions (5.4, 5.10).]
  
• Check the expiration date on the box before opening it. Do not insert Liletta after the expiration date.
  
• Visually inspect the packaging containing Liletta to verify that the packaging has not been damaged (e.g., torn, punctured, etc.).  If the packaging has any visual damage that could compromise sterility, do not use the unit for insertion [see Warnings and Precautions (5.3)].
  
• Ensure that the patient understands the contents of the Patient Information Booklet and obtain consent.  A sample consent form that includes the lot number is on the last page of the Patient Information Booklet.
  
• Complete the pelvic examination, speculum placement, tenaculum placement, and sounding of the uterus before opening the Liletta packaging.
  
• Do not open the packaging to insert Liletta if: 
  ° the cervix is unable to be properly visualized
  ° the uterus cannot be adequately instrumented (during sounding)
  ° the uterus sounds to less than 5.5 cm

Planning for Insertion

• Ensure all needed items for Liletta insertion are readily available:
  ° Gloves
  ° Speculum
  ° Sterile uterine sound
  ° Sterile tenaculum
  ° Antiseptic solution
  ° Liletta with inserter tray, sealed with a peel-off lid 
  ° Sterile, blunt-tipped scissors
  ° Additional items that may be useful could include:
        • Local anesthesia, needle, and syringe
        • Os finder and/or cervical dilators
        • Ultrasound with abdominal probe
  
• Exclude pregnancy and confirm that there are no other contraindications to the insertion and use of Liletta.
  
• Follow the insertion instructions exactly as described in order to ensure proper insertion.
  
• If you encounter cervical stenosis at any time during uterine sounding or Liletta insertion, use cervical dilators, not force, to overcome resistance. If necessary, dilation, sounding, and insertion may be performed with ultrasound guidance.
  
• Insertion may be associated with some pain and/or bleeding or vasovagal reactions (e.g., diaphoresis, syncope, bradycardia, or seizure), especially in patients with a predisposition to these conditions. Consider administering analgesics prior to insertion.

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, maintain sterility during Liletta loading and insertion; do not touch Liletta, the inside of the sterile tray, 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

The overall insertion process is conducted in 5 steps.

Step 1 – Preparation of Patient for Insertion

• With the patient comfortably in lithotomy position, do a bimanual exam to establish the size, shape, and position of the uterus and to evaluate any signs of uterine infection.
  
• Gently insert a speculum to visualize the cervix.
  
• Thoroughly cleanse the cervix and vagina with antiseptic solution.
  
• Administer cervical anesthetic, if needed.
  
• Apply a tenaculum to the cervix and use gentle traction to align the cervical canal with the uterine cavity.  If the uterus is retroverted, it may be more appropriate to grasp the lower lip of the cervix. Keep the tenaculum in position and maintain gentle traction on the cervix throughout the insertion procedure.
  
• Carefully sound the uterus to measure its depth.
  
• The uterus should sound to a depth of at least 5.5 cm. Insertion of Liletta into a uterine cavity that sounds to less than 5.5 cm may increase the incidence of expulsion, bleeding, pain, perforation, and possibly pregnancy. Liletta should not be inserted if the uterus sounds to less than 5.5 cm.  
  
• After ascertaining that the patient is appropriate for Liletta, replace contaminated glove(s) and open the packaging containing Liletta.

Step 2 – Opening the Sterile Liletta Packaging

• Remove the sealed tray containing Liletta from the box.
• Inspect the sealed tray and do not use the product if the packaging, inserter or IUS is damaged.
• Lay the tray on a flat surface with the peel-off lid side up.
• Remove peel-off lid.

Step 3 – Loading Liletta into the Inserter

• To remove the inserter from the tray, grasp the handle below the sliders and twist gently. 
      ° NOTE: Do not attempt to remove the inserter by pulling on the tube.
• Ensure both sliders (numbered 1 and 2) are fully forward (Figure 3):
      ° The handle single line marking will align with the BLUE (number 1) slider single line marking.
      ° The handle double line markings will align with the GREEN (number 2) slider double line markings.
• Grip the handle keeping your thumb or finger in the groove of the BLUE slider (over the numeral 1) and apply forward pressure while ensuring both sliders are fully forward.

Figure 3: Sliders Completely Forward for Loading Liletta

• Load Liletta into the inserter:
      ° Ensure the arms of the IUS are horizontal (aligned to the horizontal plane of the handle and flange); adjust the rotation of the IUS as needed using the flat sterile surface of the tray.
      ° While maintaining forward pressure on the blue slider, pull the threads straight back until you feel a hard stop. Ensure even tension is applied to both threads when pulling.
      ° Pull the threads upward or downward to lock the threads into the cleft at the bottom end of the handle (Figure 4); you must lock the threads in the cleft to prevent the IUS from moving out of the top of the insertion tube. Once the threads are locked in the cleft, stop holding the threads.
      ° After the IUS is loaded, continue to sustain forward pressure on the BLUE slider to maintain a hemispherical dome with the tips of the IUS.
      ° When correctly loaded, the IUS is completely within the insertion tube with the tips of the arms forming a hemispherical dome at the top of the tube (Figure 5).
      ° If the IUS is not correctly loaded, do not attempt insertion. To re-load Liletta:
            ■ Pull the BLUE slider back with your thumb until the groove becomes aligned with the GREEN slider to release the IUS.
            ■ Manually pull the threads out of the cleft.
            ■ Return the BLUE slider to the forward position and repeat the loading steps.

Figure 4: Locking the Threads in Cleft

Figure 5: Close-up of Hemispherical Dome at Tip of Tube

• Adjust the flange to the measured uterine depth based on sounding. To adjust, place the flat side of the flange in the tray notch (Figure 6) or against a sterile edge inside of the tray. Slide the insertion tube as necessary to move the flange to the correct measurement. Ensure the flat sides of the flange are in the same horizontal plane as the handle. If, at any step, there is a need to touch the flange or another sterile surface, sterile gloves should be used.

Figure 6: Adjusting the Flange

• If an adjustment to the curvature of the insertion tube is required to accommodate the anatomical orientation of the uterus, you may bend or straighten the insertion tube, but do not touch above the flange unless using sterile gloves. When bending the tube, avoid sharp bends to prevent kinking.
• Once the flange has been properly positioned, avoid contact with flange against objects that can change its position (e.g. tray, speculum, tenaculum, etc.).

Step 4 – Inserting Liletta into the Uterus

• Apply gentle traction on the tenaculum and continue to apply forward pressure on the BLUE slider while inserting the loaded insertion tube through the cervical os.  Advance the tube until the upper edge of the flange is 1.5-2 cm from the external cervical os (Figure 7). Maintain forward pressure on the BLUE slider throughout the insertion process.
      ° DO NOT advance flange to the cervix at this time.
      ° DO NOT force the inserter. If necessary, dilate the cervical canal.

Figure 7: Advancing Insertion Tube until Flange is 1.5 to 2 cm from the External Cervix

• Using your thumb or finger, gently slide only the BLUE slider back until you feel resistance. The BLUE and GREEN sliders will merge together to form a common thumb recess. Do not move the BLUE slider any more than is necessary to create the recess. Maintain the GREEN slider so that the double line markings on the slider and the insertion handle remain aligned (Figure 8). This will allow the IUS arms to open in the lower uterine segment. Do not pull the sliders back any further as this could result in premature release of the IUS at the incorrect location.

Figure 8: Releasing and Opening the Arms of the IUS

• Wait 10-15 seconds to allow for the arms of the IUS to fully open.
• Without moving the sliders, advance the inserter until the flange touches the cervix. If fundal resistance is encountered, do not continue to advance. Liletta is now in the fundal position (Figure 9).

Note: Fundal position is important to prevent expulsions.

Figure 9: Move Liletta into the Fundal Position

Step 5 – Releasing Liletta and Procedure Completion

While holding the inserter steady and maintaining its position relative to the cervix, move both sliders (BLUE and GREEN) together while maintaining the common thumb recess down toward the number 3 on the handle (Figure 10) until a click is heard and the GREEN indicator at the bottom of the handle is visible (Figure 11).

Figure 10: Releasing Liletta from the Inserter Tube

• Look at the cleft to ensure the threads were properly released (Figure 11); if not released or if a click is not heard, grasp the threads and gently pull the threads out of the cleft.

Figure 11: Green Indicator Visible and Threads Released from Cleft

• Withdraw the inserter from the uterus.
• Use blunt-tipped sharp scissors to cut the IUS threads perpendicular to the thread length, leaving about 3 cm outside of the cervix (Figure 12).  Note: Do not cut threads at an angle as this may leave sharp ends.
• Do not apply tension or pull on the threads when cutting to prevent displacing the IUS.

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:

• If you suspect the IUS is not in the correct position:
  ° Check insertion with an ultrasound or other appropriate radiologic test.
  ° If incorrect insertion is suspected, remove Liletta. Do not reinsert the same Liletta IUS after removal.

Difficult insertion

• If insertion is difficult because the uterus cannot be appropriately instrumented, consider the following measures:
  ° Use of cervical anesthesia to make sounding and manipulation more tolerable.
  ° Use of dilators to dilate the cervix if needed to allow passage of the sound or inserter.
  ° Abdominal ultrasound guidance during dilation and/or insertion.
  ° 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 uterine perforation [see Warnings and Precautions (5.5)].

2.4 Patient Counseling and Record-Keeping

• Keep a copy of the consent form and Liletta lot number for your records.
  
• Counsel the patient on what to expect following Liletta insertion. Give her the Patient Information Booklet, which includes the website address (www.Liletta.com). Discuss expected bleeding patterns with Liletta use. Review the signs and symptoms of Liletta expulsion. [See Patient Counseling Information (17)].
  
• Prescribe analgesics, if indicated.
  

2.5 Patient Follow-Up

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.

2.6 Removal of Liletta

Timing of Removal

• If pregnancy is desired, Liletta can be removed at any time.
  
• If pregnancy is not desired, Liletta can be removed at any time; however, a contraception method should be started prior to removal of Liletta [see Dosage and Administration (2.5)]. Counsel your patient that she is at risk of pregnancy if she has intercourse in the week prior to removal without use of a backup contraceptive method.
  
• Liletta should be removed after 4 years. Liletta can be replaced at the time of removal with a new Liletta if continued contraceptive protection is desired.

Planning for Removal

• Ensure all needed items for Liletta removal are readily available:
  ° Gloves
  ° Speculum
  ° Sterile forceps
  ° Additional items that may be required could include:
        • Local anesthetic, needle, and syringe
        • Os finder and/or cervical dilators
        • Ultrasound with abdominal probe
        • Sterile tenaculum
        • Antiseptic solution
        • Long, narrow forceps
  
• Removal may be associated with some pain and/or bleeding or vasovagal reactions (e.g., syncope, bradycardia, or seizure), especially in patients with a predisposition to these conditions.
  
• After removal of Liletta, examine the system to ensure that it is intact.

Removal Instructions

• With the patient comfortably in lithotomy position, place a speculum and visualize the cervix.

•When the threads of Liletta are visible:
      ° Remove the IUS by applying traction on the threads with forceps (Figure 13).
      ° The arms of the device will fold upward as it is withdrawn from the uterus.
      ° If the IUS cannot be removed with traction on the threads, perform an ultrasound examination to confirm location of the IUS, including assessment for partial or total perforation. If the IUS is in the uterus, use long, narrow forceps to grasp Liletta. Consider use of a tenaculum, cervical anesthesia, cervical dilators, and/or ultrasound guidance as needed.
      ° After removal, examine the system to ensure it is intact.
• If the threads of Liletta are not visible:
      ° Determine location of the IUS by ultrasound examination.
      ° If the IUS is in the uterine cavity, use long, narrow forceps (e.g., Alligator forceps) to grasp Liletta. Consider use of a tenaculum, cervical anesthesia, cervical dilators, and/or ultrasound guidance as needed. If Liletta cannot be removed using the above techniques, consider hysteroscopic evaluation for removal.
      ° If the IUS is not in the uterine cavity, consider an abdominal x-ray or CT scan to evaluate if the IUS is in the abdominal cavity.  Consider laparoscopic evaluation for removal, as clinically indicated.
      °After removal, examine the system to ensure it is intact.

Figure 13:        Removal of Liletta

2.7 Continuation of Contraception after Removal

• If a patient wishes to continue using Liletta or another intrauterine contraceptive, insertion can occur immediately after removal.
• If a patient with regular cycles wants to start a different birth control method, time the removal and initiation of a new method to ensure continuous contraception. Either remove Liletta during the first 7 days of the menstrual cycle and start the new method or start the new method at least 7 days prior to removing Liletta if removal is to occur at other times during the cycle.
• If a patient with irregular cycles or amenorrhea wants to start a different birth control method, start the new method at least 7 days before Liletta removal.
• If Liletta is removed but no other contraceptive method has already been started, the new contraceptive method can be started on the day Liletta is removed. The patient should use a backup barrier method of contraception (e.g., condoms and spermicide) or abstain from vaginal intercourse for 7 days to prevent pregnancy.

(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.