MIRENA (levonorgestrel-releasing intrauterine system)

MIRENA (levonorgestrel-releasing intrauterine system)

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MIRENA (levonorgestrel-releasing intrauterine system)

Mirena (levonorgestrel-releasing intrauterine system) contains 52 mg of LNG, a progestin, and is intended to provide an initial release rate of approximately 20 mcg/day of LNG.

Levonorgestrel USP, (-)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one, the active ingredient in Mirena, has a molecular weight of 312.4, a molecular formula of C21H28O2

Mirena

Mirena 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 white or almost white cylinder, made of a mixture of LNG and silicone (polydimethylsiloxane), containing a total of 52 mg LNG. The reservoir is covered by a semi-opaque silicone membrane, composed of polydimethylsiloxane and colloidal silica. The T-body is 32 mm in both the horizontal and vertical directions. The polyethylene of the T-body is compounded with barium sulfate, which makes it radiopaque. A monofilament brown polyethylene removal thread is attached to a loop at the end of the vertical stem of the T-body. The polyethylene of the removal thread contains iron oxide as a colorant

The components of Mirena, including its packaging, are not manufactured using natural rubber latex.

Inserter

Mirena is packaged sterile within an inserter. The inserter, which is used for insertion of Mirena 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 4.4 mm. The vertical stem of Mirena 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 Mirena has been placed, the inserter is discarded.

Mechanism of Action

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.

Pharmacodynamics

Mirena has mainly local progestogenic effects in the uterine cavity. The local concentrations of LNG lead to morphological changes including stromal pseudodecidualization, glandular atrophy, a leukocytic infiltration and a decrease in glandular and stromal mitoses.

Ovulation is inhibited in some women using Mirena. In a 1-year study, approximately 45% of menstrual cycles were ovulatory, and in another study after 4 years, 75% of cycles were ovulatory.

Indications and usage

Mirena is a progestin-containing intrauterine system (IUS) indicated for:

  • Prevention of pregnancy for up to 6 years
  • Treatment of heavy menstrual bleeding for women who choose to use intrauterine contraception as their method of contraception for up to 5 years.

Dosage and administration

  • Initial release rate of levonorgestrel (LNG) is 20 mcg/day; this rate is reduced to about 10 mcg/day after 5 years and 9 mcg/day after 6 years.
  • To be inserted by a trained healthcare provider using strict aseptic technique.
  • Patient should be re-examined and evaluated 4 to 6 weeks after insertion; then, yearly or more often if clinically indicated.

Contraindications

  • Pregnancy or suspicion of pregnancy. Cannot be used for post-coital contraception (emergency contraception)
  • Congenital or acquired uterine anomaly if itdistorts 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
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  • Uterine bleeding of unknown etiology
  • Untreated acute cervicitis or vaginitis or other lower genital tract infections
  • Acute liver disease or liver tumor (benign or malignant)
  • Increased susceptibility to pelvic infection
  • A previous intrauterine device (IUD) that has not been removed
  • Hypersensitivity to any component of Mirena

Warnings and precautions

  • 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 Astreptococcal 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.
  • Bleeding patterns become altered, may remain irregular and amenorrhea may ensue

Adverse effects

The most common adverse reactions (≥10% users) are alterations of menstrual bleeding patterns, abdominal/pelvic pain, amenorrhea, headache/migraine, genital discharge, and vulvovaginitis.

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 in specific populations

Pregnancy: The use of Mirena is contraindicated in pregnancy or with a suspected pregnancy and Mirena may cause adverse pregnancy outcomes. If a woman becomes pregnant with Mirena in place, the likelihood of ectopic pregnancy is increased and there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery. Remove Mirena, if possible, if pregnancy occurs in a woman using Mirena. If Mirena cannot be removed, follow the pregnancy closely.

Lactation: Published studies report the presence of LNG in human milk. Small amounts of progestins (approximately 0.1% of the total maternal doses) were detected in the breast milk of nursing mothers who used Mirena, resulting in exposure of LNG to the breastfed infants. There are no reports of adverse effects in breastfed infants with maternal use of progestin-only contraceptives. Isolated cases of decreased milk production have been reported with Mirena. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Mirena and any potential adverse effects on the breastfed child from Mirena or from the underlying maternal condition.

Females and Males of Reproductive Potential

Return to Fertility After Discontinuing Mirena: In two studies, return to fertility was investigated in a total of 229 women who desired pregnancy after study discontinuation and provided follow-up information. The probability to conceive within 12 months after removal of Mirena was approximately 80%.

Pediatric Use: Safety and efficacy of Mirena have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal females under the age of 18 as for users 18 years and older. Use of this product before menarche is not indicated.

Geriatric Use: Mirena has not been studied in women over age 65 and is not approved for use in this population.

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