Mirena Information
Mirena (Levonorgestrel) Indications And Usage
Mirena (Levonorgestrel) is recommended for women who have had at least one child.
The system should be replaced after 5 years if continued use is desired.
Mirena (Levonorgestrel) Dosage And Administration
Mirena (Levonorgestrel) contains 52 mg of levonorgestrel. Initially, levonorgestrel is released at a rate of approximately 20 mcg/day. This rate decreases progressively to half that value after 5 years.
Mirena (Levonorgestrel) is packaged sterile within an inserter. Information regarding insertion instructions, patient counseling and record keeping, patient follow-up, removal of Mirena (Levonorgestrel) and continuation of contraception after removal is provided below.
Mirena (Levonorgestrel) Dosage Forms And Strengths
Mirena (Levonorgestrel) is a levonorgestrel-releasing intrauterine system consisting of a T-shaped polyethylene frame with a steroid reservoir containing a total of 52 mg levonorgestrel.
Mirena (Levonorgestrel) Contraindications
The use of Mirena (Levonorgestrel) is contraindicated when one or more of the following conditions exist:
Mirena (Levonorgestrel) Warnings And Precautions
Evaluate women who become pregnant while using Mirena (Levonorgestrel) for ectopic pregnancy. Up to half of pregnancies that occur with Mirena (Levonorgestrel) in place are ectopic. The incidence of ectopic pregnancy in clinical trials that excluded women with risk factors for ectopic pregnancy was approximately 0.1% per year.
Tell women who choose Mirena (Levonorgestrel) about the risks of ectopic pregnancy, including the loss of fertility. Teach them to recognize and report to their physician promptly any symptoms of ectopic pregnancy. Women with a previous history of ectopic pregnancy, tubal surgery or pelvic infection carry a higher risk of ectopic pregnancy.
The risk of ectopic pregnancy in women who have a history of ectopic pregnancy and use Mirena (Levonorgestrel) is unknown. Clinical trials of Mirena (Levonorgestrel) excluded women with a history of ectopic pregnancy.
Mirena (Levonorgestrel) can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea and amenorrhea. During the first three to six months of Mirena (Levonorgestrel) use, the number of bleeding and spotting days may be increased and bleeding patterns may be irregular. Thereafter the number of bleeding and spotting days usually decreases but bleeding may remain irregular. If bleeding irregularities develop during prolonged treatment, appropriate diagnostic measures should be taken to rule out endometrial pathology.
Amenorrhea develops in approximately 20% of Mirena (Levonorgestrel) users by one year. The possibility of pregnancy should be considered if menstruation does not occur within six weeks of the onset of previous menstruation. Once pregnancy has been excluded, repeated pregnancy tests are generally not necessary in amenorrheic women unless indicated, for example, by other signs of pregnancy or by pelvic pain
In most women with heavy menstrual bleeding, the number of bleeding and spotting days may also increase during the initial months of therapy but usually decrease with continued use; the volume of blood loss per cycle progressively becomes reduced
Perforation or penetration of the uterine wall or cervix may occur during insertion although the perforation may not be detected until some time later. If perforation occurs, pregnancy may result Mirena (Levonorgestrel) must be located and removed; surgery may be required. Delayed detection of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses and erosion of adjacent viscera.
The risk of perforation may be increased in lactating women, in women with fixed retroverted uteri, and during the postpartum period. To decrease the risk of perforation postpartum, Mirena (Levonorgestrel) insertion should be delayed a minimum of 6 weeks after delivery or until uterine involution is complete. If involution is substantially delayed, consider waiting until 12 weeks postpartum. Inserting Mirena (Levonorgestrel) immediately after first trimester abortion is not known to increase the risk of perforation, but insertion after second trimester abortion should be delayed until uterine involution is complete.
Partial or complete expulsion of Mirena (Levonorgestrel) may occur .
Symptoms of the partial or complete expulsion of any lUD may include bleeding or pain. However, the system can be expelled from the uterine cavity without the woman noticing it, resulting in the loss of contraceptive protection. Partial expulsion may decrease the effectiveness of Mirena (Levonorgestrel) . As menstrual flow typically decreases after the first 3 to 6 months of Mirena (Levonorgestrel) use, an increase of menstrual flow may be indicative of an expulsion. If expulsion has occurred, Mirena (Levonorgestrel) may be replaced within 7 days of a menstrual period after pregnancy has been ruled out.
Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception because breast cancer is a hormone-sensitive tumor.
Spontaneous reports of breast cancer have been received during postmarketing experience with Mirena (Levonorgestrel) . Because spontaneous reports are voluntary and from a population of uncertain size, it is not possible to use postmarketing data to reliably estimate the frequency or establish causal relationship to drug exposure. Two observational studies have not provided evidence of an increased risk of breast cancer during the use of Mirena (Levonorgestrel) .
Mirena (Levonorgestrel) Adverse Reactions
The following most serious adverse reactions associated with the use of Mirena (Levonorgestrel) are discussed in greater detail in the section ():
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies 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 provided reflect the experience with the use of Mirena (Levonorgestrel) in the adequate and well-controlled studies for contraception (n=2,339) and heavy menstrual bleeding (n=80). For the contraception indication, Mirena (Levonorgestrel) was compared to a copper IUD (n=1,855), to another formulation of levonorgestrel intrauterine system (n=390) and to a combined oral contraceptive (n=94) in women 18 to 35 years old. The data cover more than 92,000 woman-months of exposure. For the treatment of heavy menstrual bleeding indication (n=80), the subjects included women aged 26 to 50 with confirmed heavy bleeding and exposed for a median of 183 treatment days of Mirena (Levonorgestrel) (range 7 to 295 days). The frequencies of reported adverse drug reactions represent crude incidences.
The adverse reactions seen across the 2 indications overlapped, and are reported using the frequencies from the contraception studies.
The most common adverse reactions (≥5% users) are uterine/vaginal bleeding alterations (51.9%), amenorrhea (23.9%), intermenstrual bleeding and spotting (23.4%), abdominal/pelvic pain (12.8%), ovarian cysts (12%), headache/migraine (7.7%), acne (7.2%), depressed/altered mood (6.4%), menorrhagia (6.3%), breast tenderness/pain (4.9%), vaginal discharge (4.9%) and IUD expulsion (4.9%).
Other relevant adverse reactions occurring in
Mirena (Levonorgestrel) Drug Interactions
Drugs or herbal products that induce enzymes, including CYP3A4, that metabolize progestins may decrease the serum concentrations of progestins.
Some drugs or herbal products that may decrease the serum concentration of levonorgestrel include:
Significant changes (increase or decrease) in the serum concentrations of the progestin have been noted in some cases of co-administration with HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.
Consult the labeling of all concurrently used drugs to obtain further information about interactions with Mirena (Levonorgestrel) or the potential for enzyme alterations.
Mirena (Levonorgestrel) Description
Mirena (Levonorgestrel) is intended to provide an initial release rate of 20 mcg/day of levonorgestrel
Levonorgestrel USP, (-)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one, the active ingredient in Mirena (Levonorgestrel) , has a molecular weight of 312.4, a molecular formula of CHO, and the following structural formula:
Mirena (Levonorgestrel) Clinical Pharmacology
Mirena (Levonorgestrel) has mainly local progestogenic effects in the uterine cavity. The high local levels of levonorgestrel 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 (Levonorgestrel) . In a 1-year study approximately 45% of menstrual cycles were ovulatory and in another study after 4 years 75% of cycles were ovulatory.
Mirena (Levonorgestrel) Clinical Studies
Mirena (Levonorgestrel) has been studied for safety and efficacy in two large clinical trials in Finland and Sweden. In study sites having verifiable data and informed consent, 1,169 women 18 to 35 years of age at enrollment used Mirena (Levonorgestrel) for up to 5 years, for a total of 45,000 women-months of exposure. Subjects had previously been pregnant, had no history of ectopic pregnancy, had no history of pelvic inflammatory disease over the preceding 12 months, were predominantly Caucasian, and over 70% of the participants had previously used IUDs (intrauterine devices). The reported 12-month pregnancy rates were less than or equal to 0.2 per 100 women (0.2%) and the cumulative 5-year pregnancy rate was approximately 0.7 per 100 women (0.7%).
About 80% of women wishing to become pregnant conceived within 12 months after removal of Mirena (Levonorgestrel) .
The efficacy of Mirena (Levonorgestrel) in the treatment of heavy menstrual bleeding was studied in a randomized, open-label, active-control, parallel-group trial comparing Mirena (Levonorgestrel) (n=79) to an approved therapy, medroxyprogesterone acetate (MPA) (n=81), over 6 cycles. The subjects included reproductive-aged women in good health, with no contraindications to the drug products and with confirmed heavy menstrual bleeding (≥ 80 mL menstrual blood loss [MBL]) determined using the alkaline hematin method. Excluded were women with organic or systemic conditions that may cause heavy uterine bleeding (except small fibroids, with total volume not > 5 mL). Treatment with Mirena (Levonorgestrel) showed a statistically significantly greater reduction in MBL and a statistically significantly greater number of subjects with successful treatment Successful treatment was defined as proportion of subjects with (1) end-of-study MBL
Mirena (Levonorgestrel) How Supplied/storage And Handling
Mirena (Levonorgestrel) (levonorgestrel-releasing intrauterine system), containing a total of 52 mg levonorgestrel, is available in a carton of one sterile unit NDC# 50419-421-01. Each Mirena (Levonorgestrel) is packaged together with an inserter in a thermoformed blister package with a peelable lid.
Mirena (Levonorgestrel) is supplied sterile. Mirena (Levonorgestrel) is sterilized with ethylene oxide. Do not resterilize. For single use only. Do not use if the inner package is damaged or open. Insert before the end of the month shown on the label.
Store at 25°C (77°F); with excursions permitted between 15–30°C (59–86°F) [see USP Controlled Room Temperature].
Mirena (Levonorgestrel)
Mirena (Levonorgestrel)
