Mirena

Contraception

Mirena is indicated for prevention of pregnancy for up to 8 years; replace after the end of the eighth year.

Heavy Menstrual Bleeding

Mirena is indicated for the treatment of heavy menstrual bleeding for up to 5 years in women who choose to use intrauterine contraception as their method of contraception; replace after the end of the fifth year if continued treatment of heavy menstrual bleeding is needed.

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)].

Insertion Instructions

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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 and Warnings and Precautions .] 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 ].

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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.

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Check expiration date of Mirena prior to initiating insertion.

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Mirena should be inserted by a trained healthcare provider. Healthcare providers should become thoroughly familiar with the insertion instructions before attempting insertion of Mirena.

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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.

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

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Open the package (Figure 1). The contents of the package are sterile.

Figure 1: Opening the Mirena Package

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Using sterile gloves lift the handle of the sterile inserter and remove from the sterile package.

Step 2–Load Mirena into the insertion tube

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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

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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.

Step 3–Setting the Flange

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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

Step 4–Mirena is now ready to be inserted

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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.

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

Step 6–Advance to fundal position

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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

Step 7–Release Mirena and withdraw the inserter

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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

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Continue to hold the slider all the way down while you slowly and gently withdraw the inserter from the uterus.

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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.

Patient Follow-up

Reexamine and evaluate patients 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated.

Removal of Mirena

Removal Procedure

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Remove Mirena by applying gentle traction on the threads with forceps. (Figure 9).

Figure 9: Removal of Mirena

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If the threads are not visible, determine location of Mirena by ultrasound [see Warnings and Precautions ].

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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.

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If unable to remove with gentle traction, determine Mirena location and exclude perforation by ultrasound or other imaging [see Warnings and Precautions ( 5.10)].

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Removal may be associated with:

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pain and/or bleeding, vasovagal reactions (for example, syncope, bradycardia) or seizure, especially in patients with a predisposition to these conditions.

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breakage or embedment of Mirena in the myometrium that can make removal difficult [see Warnings and Precautions ]. Analgesia, paracervical anesthesia, cervical dilation, alligator forceps or other grasping instrument, or hysteroscopy may be used to assist in removal.

Continuation of Contraception after Removal

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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.

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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.

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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.

Pregnancy

Lactation

Females and Males of Reproductive Potential

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.

Risk of Ectopic Pregnancy

Evaluate women for ectopic pregnancy if they become pregnant with Mirena in place because the likelihood of a pregnancy being ectopic is increased with Mirena. Approximately one-half of pregnancies that occur with Mirena in place are likely to be ectopic. Also consider the possibility of ectopic pregnancy in the case of lower abdominal pain, especially in association with missed menses or if an amenorrheic woman starts bleeding.

The incidence of ectopic pregnancy in clinical trials with Mirena, which excluded women with a history of ectopic pregnancy, was approximately 0.1% per year. The risk of ectopic pregnancy, in women who have a history of ectopic pregnancy and use Mirena is unknown. Women with a previous history of ectopic pregnancy, tubal surgery or pelvic infection carry a higher risk of ectopic pregnancy. Ectopic pregnancy may result in loss of fertility.

Risks with Intrauterine Pregnancy

If pregnancy occurs while using Mirena, remove Mirena because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal of Mirena or probing of the uterus may also result in spontaneous abortion. In the event of an intrauterine pregnancy with Mirena, consider the following:

Sepsis

Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of Mirena. In some cases, severe pain occurred within hours of insertion followed by sepsis within days. Because death from GAS is more likely if treatment is delayed, it is important to be aware of these rare but serious infections. Aseptic technique during insertion of Mirena is essential in order to minimize serious infections such as GAS.

Pelvic Infection

Promptly examine users with complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding, fever, genital lesions or sores. Remove Mirena in cases of recurrent endometritis or PID, or if an acute pelvic infection is severe or does not respond to treatment.

Perforation

Perforation (total or partial, including penetration/embedment of Mirena in the uterine wall or cervix) may occur most often during insertion, although the perforation may not be detected until sometime later. The incidence of perforation during clinical trials, which excluded breast-feeding women, was < 0.1%.

The risk of uterine perforation is increased in women who have recently given birth, and in women who are breastfeeding at the time of insertion. In a large postmarketing safety study conducted in the US, the risk of uterine perforation was highest when insertion occurred within ≤ 6 weeks postpartum, and also higher with breastfeeding at the time of insertion [see Adverse Reactions ( 6.2)].

The risk of perforation may be increased if Mirena is inserted when the uterus is fixed, retroverted or not completely involuted.

If perforation occurs, locate and remove Mirena. Surgery may be required. Delayed detection or removal of Mirena in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses and erosion of adjacent viscera. In addition, perforation may reduce contraceptive efficacy and result in pregnancy.

Expulsion

Partial or complete expulsion of Mirena may occur resulting in the loss of efficacy. Expulsion may be associated with symptoms of bleeding or pain, or it may be asymptomatic and go unnoticed. Mirena typically decreases menstrual bleeding over time; therefore, an increase of menstrual bleeding may be indicative of an expulsion. Consider further diagnostic imaging, such as x-ray, if expulsion is suspected based on ultrasound [see Warnings and Precautions (5.10)]. In clinical trials, a 4.5% expulsion rate was reported over the 5-year study duration.

The risk of expulsion is increased with insertions immediately after delivery and appears to be increased with insertion after second-trimester abortion based on limited data. In a large postmarketing safety study conducted in the US, the risk of expulsion was lower with breastfeeding status [see Adverse Reactions ( 6.2)].

Remove a partially expelled Mirena. If expulsion has occurred, a new Mirena can be inserted any time the provider can be reasonably certain the woman is not pregnant.

Ovarian Cysts

Because the contraceptive effect of Mirena is mainly due to its local effects within the uterus, ovulatory cycles with follicular rupture usually occur in women of fertile age using Mirena. Ovarian cysts have been reported in approximately 8% of women using Mirena. Most cysts are asymptomatic, although some may be accompanied by pelvic pain or dyspareunia.

In most cases the ovarian cysts disappear spontaneously during two to three months observation. Evaluate persistent ovarian cysts. Surgical intervention is not usually required.

Bleeding Pattern Alterations

Mirena can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea and amenorrhea. During the first 3–6 months of Mirena use, the number of bleeding and spotting days may be higher 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 users by one year.

If a significant change in bleeding develops during prolonged use, take appropriate diagnostic measures to rule out endometrial pathology. Consider the possibility of pregnancy 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 [see Clinical Studies ( 14.1)].

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 [see Clinical Studies ( 14.2)].

Breast Cancer

Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception, including Mirena, because some breast cancers are hormone-sensitive [see Contraindications ( 4)].

Spontaneous reports of breast cancer have been received during postmarketing experience with Mirena. Observational studies of the risk of breast cancer with use of a LNG-releasing IUS do not provide conclusive evidence of increased risk.

Clinical Considerations for Use and Removal

Use Mirena with caution after careful assessment if any of the following conditions exist, and consider removal of the system if any of them arise during use:

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Coagulopathy or use of anticoagulants

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Migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia

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Exceptionally severe headache

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Marked increase of blood pressure

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Severe arterial disease such as stroke or myocardial infarction

In addition, consider removing Mirena if any of the following conditions arise during use [see Contraindications ( 4)]:

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Uterine or cervical malignancy

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Jaundice

If the threads are not visible or are significantly shortened, they may have broken or retracted into the cervical canal or uterus. Consider the possibility that the system may have been displaced (for example, expelled or perforated the uterus) [see Warnings and Precautions ]. Exclude pregnancy and verify the location of Mirena, for example, by sonography, X-ray, or by gentle exploration of the cervical canal with a suitable instrument. If Mirena is displaced, remove it. A new Mirena may be inserted at that time or during the next menses if it is certain that conception has not occurred. If Mirena is in place with no evidence of perforation, no intervention is indicated.