Levonorgestrel

Mirena is a progestin-containing intrauterine system (IUS) indicated for: • Prevention of pregnancy for up to 8 years. • Treatment of heavy menstrual bleeding for women who choose to use intrauterine contraception as their method of contraception for up to 5 years.

The local mechanism by which continuously released LNG contributes to the contraceptive effectiveness of Mirena has not been conclusively demonstrated. Studies of Mirena and similar LNG IUS prototypes have suggested several mechanisms that prevent pregnancy: thickening of cervical mucus preventing passage of sperm into the uterus, inhibition of sperm capacitation or survival, and alteration of the endometrium.

• 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. • 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.

The use of Mirena is contraindicated when one or more of the following conditions exist: • Pregnancy or suspicion of pregnancy • For use as post-coital contraception (emergency contraception) • Congenital or acquired uterine anomaly including fibroids, that distorts the uterine cavity • Acute pelvic inflammatory disease (PID) or a history of PID unless there has been a subsequent intrauterine pregnancy • Postpartum endometritis or infected abortion in the past 3 months • Known or suspected uterine or cervical malignancy • Known or suspected breast cancer or other progestin-sensitive cancer, now or in the past • Uterine bleeding of unknown etiology • Untreated acute cervicitis or vaginitis…

• Remove Mirena if pregnancy occurs with Mirena 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 Mirena, 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 or 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.

The following serious or otherwise important adverse reactions are discussed in elsewhere in the labeling: • Ectopic Pregnancy • Intrauterine Pregnancy • Group A Streptococcal Sepsis (GAS) • Pelvic Inflammatory Disease • Perforation • Expulsion • Ovarian Cysts • Bleeding Pattern Alterations The most common adverse reactions (≥10% users) are alterations of menstrual bleeding patterns, abdominal/pelvic pain, amenorrhea, headache/migraine, genital discharge, and vulvovaginitis.

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.

Store at 25°C (77°F), with excursions permitted between 15–30°C (59–86°F).