LEVONORGESTREL

7 DRUG INTERACTIONS No drug-drug interaction studies have been conducted with Mirena. 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 Mirena. However, the contraceptive effect of Mirena is mediated via the direct release of LNG into the uterine cavity and is unlikely to be affected by drug interactions via enzyme induction or inhibition.

Use for women to reduce chance of pregnancy after unprotected sex (if a contraceptive failed or if you did not use birth control)

2 DOSAGE AND ADMINISTRATION • Release rate of levonorgestrel (LNG) is 21 mcg/day after 24 days; this rate is reduced to about 11 mcg/day after 5 years and 7 mcg/day after 8 years. ( 2.1 ) • To be inserted by a trained healthcare provider using strict aseptic technique. Follow insertion instructions exactly as described. ( 2.2 ) • Patient should be re-examined and evaluated 4 to 6 weeks after insertion; then, yearly or more often if clinically indicated. ( 2.3 ) 2.1 Dosing Over Time Mirena contains 52 mg of levonorgestrel (LNG) released in vivo, at a rate of approximately 21 mcg/day after 24 days. This rate decreases progressively to approximately 11 mcg/day after 5 years and 7 mcg/day after 8 years. For contraception, remove Mirena by the end of the eighth year and replace at the time of removal with a new Mirena if continued use is desired. For treatment of heavy menstrual bleeding, replace Mirena by the end of the fifth year if continued use is needed because data on use in this indication beyond 5 years are limited. Mirena is supplied in a sterile package within an inserter that enables single-handed loading (see Figure 1). Do not open the package until required for insertion [see Description ( 11.2 )]. Do not use if the seal of the sterile package is broken or appears compromised. Use strict aseptic techniques throughout the insertion procedure [see Warnings and Precautions ( 5.3 )] . Mirena and Inserter 2.2 Insertion Instructions • Obtain a complete medical and social history to determine conditions that might influence the selection of a levonorgestrel-releasing intrauterine system (LNG IUS) for contraception . If indicated, perform a physical examination, and appropriate tests for any forms of genital or other sexually transmitted infections. [See Contraindications ( 4 ) and Warnings and Precautions ( 5.10 ).] Because irregular bleeding/spotting is common during the first months of Mirena use, exclude endometrial pathology (polyps or cancer) prior to the insertion of Mirena in women with persistent or uncharacteristic bleeding [see Warnings and Precautions ( 5.8 )]. • Follow the insertion instructions exactly as described to ensure proper placement and avoid premature release of Mirena from the inserter. Once released, Mirena cannot be re-loaded . • Check expiration date of Mirena prior to initiating insertion. • Mirena should be inserted by a trained healthcare provider. Healthcare providers should become thoroughly familiar with the insertion instructions before attempting insertion of Mirena. • 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 Mirena Starting Mirena in women not currently using hormonal or intrauterine contraception • Insert Mirena any time there is reasonable certainty that the woman is not pregnant. Consider the possibility of ovulation and conception prior to initiation of this product [see Contraindications (4)]. • If Mirena 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 Mirena 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 Mirena from an oral, transdermal, or vaginal hormonal contraceptive • Insert Mirena 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 Mirena insertion or until the end of the current treatment cycle. • If the woman was using continuous hormonal contraception, discontinue that method seven days after Mirena insertion. Switching to Mirena from an injectable progestin contraceptive • Insert Mirena at any time; a non-hormonal back-up birth control (such as condoms or spermicide) should also be used for 7 days if Mirena is inserted more than 3 months (13 weeks) after the last injection. Switching to Mirena from a contraceptive implant or another IUS • Insert Mirena on the same day the implant or IUS is removed. • Insert Mirena at any time during the menstrual cycle. Inserting Mirena after first-trimester abortion or miscarriage • Insert Mirena immediately after a first-trimester abortion or miscarriage, unless it is a septic abortion [see Contraindications ( 4 )]. Inserting Mirena after childbirth or second-trimester abortion or miscarriage • Immediate insertion after childbirth or second-trimester abortion or miscarriage • Insert Mirena after removal of the placenta. Back-up contraception is not needed. [See Contraindications ( 4 ), Warnings and Precautions ( 5.5 , 5.6 ), Adverse Reactions ( 6.2 )]. Interval insertion following complete involution of the uterus • Wait a minimum of 6 weeks or until the uterus is fully involuted before inserting Mirena [see Warnings and Precautions ( 5.5 , 5.6 ), Adverse Reactions ( 6.2 )]. • Insert Mirena any time there is reasonable certainty the woman is not pregnant. • If Mirena 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 [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )]. Tools for Insertion Note: The inserter provided with Mirena (see Figure 1) 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 Mirena from the inserter by first loading (see Figure 2) and then releasing (see Figure 7) Mirena from the inserter, and insert according to accepted practice. Preparation • Gloves • Speculum • Sterile uterine sound • Sterile tenaculum • Antiseptic solution, applicator Procedure • Sterile gloves • Mirena with inserter in sealed package • Instruments and anesthesia for paracervical block, if anticipated • Consider having an unopened back-up Mirena available • Sterile, sharp curved scissors Preparation for insertion • Exclude pregnancy and confirm that there are no other contraindications to the use of Mirena. • 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. • The uterus should sound to a depth of 6 to 10 cm. Insertion of Mirena into a uterine cavity less than 6 cm by sounding may increase the incidence of expulsion, bleeding, pain, perforation, and possibly pregnancy. Insertion Procedure Proceed with insertion only after completing the above steps and ascertaining that the patient is appropriate for Mirena. 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 Mirena Package • Using sterile gloves lift the handle of the sterile inserter and remove from the sterile package. Figure 1 Step 2–Load Mirena 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 Mirena T-body to load Mirena 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 Mirena • 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 Mirena. Once the slider is moved below the mark, Mirena cannot be re-loaded. Fig 2 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 Fig 3 Step 4–Mirena 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. Advamcing insertion tube Step 5–Open the arms While holding the inserter steady, move the slider down to the mark to release the arms of Mirena (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 Fig 5 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. Mirena is now in the fundal position (Figure 6). Fundal positioning of Mirena is important to prevent expulsion. Figure 6: Move Mirena into the fundal position Fig 6 Step 7–Release Mirena and withdraw the inserter • Holding the entire inserter firmly in place, release Mirena by moving the slider all the way down (Figure 7). Figure 7: Move the slider all the way down to release Mirena 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 Mirena. Figure 8: Cutting the threads Mirena insertion is now complete. Prescribe analgesics, if indicated. Record the Mirena lot number in the patient records. Fig 7 Fig 8 Important information to consider during or after insertion • If you suspect that Mirena is not in the correct position, check placement (for example, using transvaginal ultrasound). Remove Mirena if it is not positioned completely within the uterus. Do not reinsert a removed Mirena. • 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. 2.3 Patient Follow-up Reexamine and evaluate patients 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated. 2.4 Removal of Mirena Timing of Removal • For contraception, remove Mirena by the end of the eighth year and replace at the time of removal with a new Mirena if continued use is desired. Replace Mirena by the end of the fifth year if continued treatment of heavy menstrual bleeding is needed. • If pregnancy is not desired, remove Mirena 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. [See Dosage and Administration ( 2.5 ).] Tools for Removal Preparation • Gloves • Speculum Procedure • Sterile forceps Removal Procedure • Remove Mirena by applying gentle traction on the threads with forceps. (Figure 9). Figure 9: Removal of Mirena • If the threads are not visible, determine location of Mirena by ultrasound [see Warnings and Precautions ( 5.10 )] . • If Mirena 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 Mirena, examine the system to ensure that it is intact. The hormone cylinder may slide over and cover the horizontal arms, giving the appearance of missing arms. This situation generally does not require further intervention once the system is verified to be intact. • If unable to remove with gentle traction, determine Mirena location and exclude perforation by ultrasound or other imaging [ see Warnings and Precautions ( 5.10 )]. • Removal may be associated with: o pain and/or bleeding, vasovagal reactions (for example, syncope, bradycardia) or seizure, especially in patients with a predisposition to these conditions. o breakage or embedment of Mirena in the myometrium that can make removal difficult [see Warnings and Precautions ( 5.5 )] . Analgesia, paracervical anesthesia, cervical dilation, alligator forceps or other grasping instrument, or hysteroscopy may be used to assist in removal. fig 9 2.5 Continuation of Contraception after Removal • If pregnancy is not desired and if a woman wishes to continue using Mirena, 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 Mirena 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 Mirena 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.