Clinical Review

What’s the gist of a new FDA label for the LNG-IUS?

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Important changes for practice affect insertion and use of the Mirena device, selection of candidates, contraindications, and adverse effects



Since the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena, Bayer Health Care Pharmaceuticals) ( FIGURE 1 ) was introduced in the United States in 2001, more than 2 million devices have been used by women here. This use has contributed to a cumulative experience of 14 million women (36 million woman-years of experience) in 120 countries over the last 18 years.

Recent Food and Drug Administration (FDA)-approved labeling changes for the LNG-IUS1 expand the pool of women who are candidates for this convenient, reversible method of contraception. This article summarizes those labeling changes and answers questions that are often asked by clinicians who, more and more, insert the LNG-IUS for their patients.

FIGURE 1 LNG-IUS, arms open

The LNG-IUS device is readily visible on radiographs. Visualization by ultrasonography is more challenging.


What changes have been made to labeling?

Patient profile. The so-called recommended patient profile has been streamlined. The label now indicates only that the LNG-IUS is recommended for women who have given birth to at least one child. A more detailed description of women who were included in the phase-II US clinical trial is included in that section of the labeling. Clinicians should recognize that neither nulliparity nor nulligravity is listed in labeling as a contraindication to the LNG-IUS.

Depth of cavity. Another important change in the new labeling is that the LNG-IUS can be used in women whose uterine cavity sounds to a depth of 6 to 10 cm (no longer only 6 to 9 cm). This will permit more multiparous women, who may have a larger cavity, to use the LNG-IUS.

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Pregnancy risk and consequences. The risk of pregnancy is rare when the LNG-IUS is used; pregnancy with the device in situ does not appear to be associated with an increased risk of birth defects. As of September 2006, there had been only 390 live births among an estimated cumulative 9.9 million LNG-IUS users worldwide. Of those births, congenital anomalies have been infrequent; no clear trend was seen toward an increased risk of any specific anomaly after exposure to the LNG-IUS.

Adverse events. As worldwide experience with the LNG-IUS has expanded since the last labeling, the number of reported cases of relatively rare adverse events has also been updated:

  • Only nine cases of infection with group A Streptococcus have been reported in 9.9 million users, constituting a risk of approximately one infection for every 1 million users
  • Based on postmarketing experience, new wording has been added about the possibility of 1) device breakage (before insertion) and 2) angioedema—a rare allergic reaction that is not specific to levonorgestrel (or the IUS)
  • Wording has been added to the labeling that provides reassurance, based on observational studies, that there is no evidence of an increase in the risk of breast cancer risk with use of the LNG-IUS
  • Similarly, the new labeling declares that, in general, no adverse eff ects have been found with use of the LNG-IUS on breast-feeding performance in regard to the health, growth, or development of an infant—even though isolated cases of a decrease in milk production have been reported.

Contraindications. The roster of contraindications ( TABLE ) has been significantly modified to reflect scientific evidence. Removed from that list are 1) a history of ectopic pregnancy and 2) risk factors for ectopic pregnancy.

TABLE A new label lists 12 contraindications to the LNG-IUS

The LNG-IUS is contraindicated in the presence of one or more of the following:
Pregnancy or suspicion of pregnancy
Congenital or acquired uterine anomaly, including fibroids if they distort the uterine cavity
Acute pelvic inflammatory disease or a history of pelvic inflammatory disease, unless there has been a subsequent intrauterine pregnancy
Postpartum endometritis or infected abortion in the past 3 months
Known or suspected uterine or cervical neoplasia or unresolved, abnormal Pap smear
Genital bleeding of unknown cause
Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infection, until infection is controlled
Acute liver disease or liver tumor (benign or malignant
Conditions associated with an increased susceptibility to pelvic infection
Previously inserted intrauterine device that has not been removed
Hypersensitivity to any device component
Known or suspected carcinoma of the breast

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