Levonorgestrel Intrauterine

Levonorgestrel Intrauterine is a prescription medicine used as contraception to prevent pregnancy and to treat heavy menstrual bleeding.

• Levonorgestrel Intrauterine is available under the following different brand names: Mirena, Skyla, Liletta, Kyleena

Adult and pediatric dosage

Levonorgestrel-releasing Intrauterine system

• 13.5mg/device (Skyla)
• 19.5mg/device (Kyleena)
• 52mg/device (Liletta, Mirena)

Contraception

Adult dosage

Mirena

• The initial levonorgestrel release rate is 20 mcg/day; the rate decreases to approximately 10 mcg/day after 5 years and 8 mcg/day after 7 years
• Remove by 7 years following insertion and replace if continuing treatment

Skyla

• The levonorgestrel release rate is 14 mcg/day after 24 days and 5 mcg/day after 3 years
• May remove and replace with a new unit anytime during the menstrual cycle
• Must be removed or replaced by 3 years following insertion

Liletta

• Initially, the levonorgestrel release rate is approximately 20 mcg/day; the rate decreases progressively to approximately 8.6 mcg/day after 6 years
• The average in vivo release rate is approximately 14.3 mcg/day over a period of 6 years
• May remove and replace with a new unit anytime during the menstrual cycle
• Must be removed or replaced by the end of the sixth year following insertion

Kyleena

• The release rate is 17.5 mcg/day after 24 days and declines to 7.4 mcg/day after 5 years
• May remove and replace with a new unit anytime during the menstrual cycle
• Must be removed or replaced by 5 years following insertion

Pediatric dosage

Postpubertal females

Skyla

• The levonorgestrel release rate is 14 mcg/day after 24 days and 5 mcg/day after 3 years
• May remove and replace with a new unit anytime during the menstrual cycle
• Must be removed or replaced by 3 years following insertion

Liletta

• Initially, the levonorgestrel release rate is approximately 20 mcg/day; the rate decreases progressively to approximately 8.6 mcg/day after 6 years
• The average in vivo release rate is approximately 14.3 mcg/day over 6 years
• May remove and replace with a new unit anytime during the menstrual cycle
• Must be removed or replaced by the end of the sixth year following insertion

Mirena

• The initial levonorgestrel release rate is 20 mcg/day; the rate reduced by 50% after 5 years
• May remove and replace with a new unit anytime during the menstrual cycle
• Must be removed or replaced by 5 years following insertion

Kyleena

• The release rate is 17.5 mcg/day after 24 days and declines to 7.4 mcg/day after 5 years
• May remove and replace with a new unit anytime during the menstrual cycle
• Must be removed or replaced by 5 years following insertion

Heavy Menstrual Bleeding

Adult dosage

• Indicated for heavy menstrual bleeding for up to 5 years in women who choose to use Intrauterine contraception as a method of contraception
• The initial levonorgestrel release rate is 20 mcg/day; the rate reduced by 50% after 5 years
• Replace after the end of the fifth year if continued treatment needed

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Levonorgestrel Intrauterine include:

• pelvic pain,
• vaginal itching or infection,
• irregular menstrual periods,
• changes in bleeding patterns or flow,
• stomach pain,
• nausea,
• vomiting,
• bloating,
• headache,
• depression,
• mood changes,
• back pain,
• breast tenderness or pain,
• weight gain,
• acne,
• changes in hair growth,
• loss of interest in sex,
• puffiness in the face, hands, ankles, or feet
• ovarian cysts,
• pelvic pain,
• abdominal cramps,
• increased vaginal bleeding,
• depression,
• hair loss,
• amenorrhea, and 
• vulvovaginitis.

Serious side effects of Levonorgestrel Intrauterine include:

• severe cramps or pelvic pain,
• pain during intercourse,
• extreme dizziness,
• lightheadedness,
• severe migraine headache,
• heavy or ongoing vaginal bleeding,
• vaginal sores,
• watery vaginal discharge, foul-smelling discharge, or otherwise unusual,
• pale skin,
• weakness,
• easy bruising or bleeding,
• fever,
• chills,
• signs of infection,
• sudden numbness or weakness (especially on one side of the body),
• confusion,
• vision problems,
• sensitivity to light,
• yellowing of the skin or eyes (jaundice),
• hives,
• difficulty breathing,
• swelling of face, lips, tongue or throat,
• increased vaginal bleeding, and
• devise expulsion.

Rare side effects of Levonorgestrel Intrauterine include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Levonorgestrel Intrauterine has severe interactions with no other drugs.
• Levonorgestrel Intrauterine has serious interactions with at least 26 other drugs.
• Levonorgestrel Intrauterine has moderate interactions with at least 40 other drugs.
• Levonorgestrel Intrauterine has minor interactions with the following drug:
  • levoketoconazole 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Pregnancy or suspicion of pregnancy; cannot be used for postcoital contraception (emergency contraception)
• 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
• 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, including bacterial vaginosis or other lower genital tract infections until infection, is controlled
• Acute liver disease or liver tumor (benign or malignant)
• Conditions associated with increased susceptibility to pelvic infections
• Previously inserted Intrauterine device (IUD) that has not been removed
• Hypersensitivity to any component of this product

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Levonorgestrel Intrauterine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Levonorgestrel Intrauterine?”

Cautions

• Pregnant women whose device cannot be removed or if the patient chooses not to have it removed increases risk of miscarriage, sepsis, premature labor, and premature delivery; advise the patient of isolated reports of virilization of the female fetus following local exposure to the drug during pregnancy with an IUS in place
• Evaluate women for ectopic pregnancy; Approximately 50% of pregnancies that occur with IUD are likely to be ectopic; also consider the possibility of ectopic pregnancy in case of lower abdominal pain, especially in association with missed menses or if an amenorrheic woman starts bleeding
• Severe infection, including group A streptococcal sepsis, reported
• Bleeding pattern alterations may occur, including amenorrhea, infrequent bleeding, prolonged bleeding, or irregular bleeding
• Perforation may occur, most often during insertion; an interim analysis from a large postmarketing safety study shows an increased risk of perforation in lactating women; perforation risk may be increased in women with fixed retroverted uteri, and during the postpartum period; perforation may also occur at any time during IUS use; perforation may reduce contraceptive efficacy and result in pregnancy; this may be associated with severe pain and continued bleeding
• Inform women who use the product about recognizing signs and symptoms of ectopic pregnancy and promptly reporting them to their healthcare professional, and about the associated risks of ectopic pregnancy (eg, loss of fertility)
• Exclude underlying endometrial pathology (eg, polyps or cancer) before insertion of device in women with persistent or uncharacteristic bleeding; irregular bleeding/spotting is common during the first months of use and may preclude adequate assessment after insertion
• 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 IUS may have been displaced, (for example, expulsed or perforated the uterus); exclude pregnancy and verify the location of the device by an appropriate diagnostic method
• Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception, because some breast cancers are hormone-sensitive
• Product not intended for use in menopausal women
• Women with symptomatic actinomycosis should have the device removed and should receive antibiotics
• Ovarian cysts may occur
• Assess whether the woman is at increased risk of infection (eg, leukemia, acquired immune deficiency syndrome [AIDS], IV drug abuse), or has a history of PID unless there has been a subsequent Intrauterine pregnancy; the device does not protect against HIV/STI transmission
• Pelvic infection
  • PID may be asymptomatic but still result in tubal damage and its sequelae
  • Promptly examine users with complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding, fever, genital lesions, or sores; remove the device in cases of recurrent endometritis or PID, or if an acute pelvic infection is severe or does not respond to treatment
  • IUDs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion
  • PID is often associated with a sexually transmitted infection (STI), and Mirena does not protect against STI; the risk of PID is greater for women who have multiple sexual partners, and also for women whose sexual partner(s) have multiple sexual partners
  • Women who have had PID are at increased risk for a recurrence or re-infection; in particular, ascertain whether the woman is at increased risk of infection (for example, leukemia, acquired immune deficiency syndrome [AIDS], intravenous drug abuse)
  • Following a diagnosis of PID, or suspected PID, obtain bacteriologic specimens and initiate antibiotic therapy promptly; removal of the device after initiation of antibiotic therapy is usually appropriate
• Perforation
  • Perforation may occur, most often during insertion; an interim analysis from a large postmarketing safety study shows an increased risk of perforation in lactating women
  • 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 and during the postpartum period; the risk of perforation may be increased if the device is inserted when the uterus is fixed, retroverted or not completely involuted
  • Perforation may also occur at any time during IUS use and may reduce contraceptive efficacy and result in pregnancy; this may be associated with severe pain and continued bleeding
  • If perforation occurs, locate, and remove the device; surgery may be required; delayed detection or removal of the device in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses, and erosion of adjacent viscera
• Bleeding pattern alterations
  • The device can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea, and amenorrhea; during the first 3–6 months of use, the number of bleeding and spotting days may be higher, and bleeding patterns may be irregular
  • Thereafter number of bleeding and spotting days usually decreases but bleeding may remain irregular; if bleeding irregularities develop during prolonged treatment, take appropriate diagnostic measures to rule out endometrial pathology
  • Amenorrhea develops in approximately 20% of device users by one year
  • 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
  • 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
• Expulsion
  • Partial or complete expulsion of the Intrauterine device may occur resulting in loss of contraceptive protection; expulsion may be associated with symptoms of bleeding or pain, or it may be asymptomatic and go unnoticed
  • The drug typically decreases menstrual bleeding over time; an increase in menstrual bleeding may be indicative of an expulsion
  • Consider further diagnostic imaging, such as x-ray, if expulsion is suspected based on ultrasound
  • 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
  • Remove a partially expelled device; if expulsion has occurred, a new device can be inserted any time the provider can be reasonably certain the woman is not pregnant
  • A 5-year expulsion rate of 3.5% (59 out of 1,690 subjects) was reported in clinical trials; delay insertion a minimum of 4 weeks or until uterine involution complete following a delivery or a second-trimester abortion
• MRI
  • Safe scanning with MRI may occur under specific conditions
  • static magnetic field less than or equal to 3 Tesla
  • spatial gradient field less than or equal to 36,000 Gauss/cm (T/m)
  • maximum SAR (whole-body) of 4W/kg in first-level controlled mode for 15 min
• Clinical Considerations for Use and Removal
  • Coagulopathy or use of anticoagulants
  • Migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia
  • Exceptionally severe headache
  • Marked increase of blood pressure
  • Severe arterial diseases such as stroke or myocardial infarction
  • Consider removing the device if jaundice or uterine or cervical malignancy occur during use
• Drug interaction overview
  • Drug interactions not studied; drugs or herbal products that induce or inhibit drug-metabolizing enzymes, including CYP3A4, may decrease or increase, respectively, the serum concentrations of the drug during use; however, contraceptive effect of the drug is mediated via direct release of the drug into the uterine cavity and is unlikely to be affected by drug interactions via enzyme induction or inhibition

Pregnancy and Lactation

• Contraindicated in pregnancy or suspected pregnancy
• If a female becomes pregnant with IUD in place, the risk of ectopic pregnancy is increased as well as miscarriage, sepsis, premature labor, and premature delivery
• Isolated cases of virilization of the external genitalia of female fetus following exposure to levonorgestrel during pregnancy with a levonorgestrel Intrauterine device in place
• Remove IUD, if possible, if pregnancy occurs in a woman using IUD
• If a woman becomes pregnant with a levonorgestrel Intrauterine device in place and the woman chooses not to have it removed or can’t be removed, advise her of reports of virilization of the female fetus following local exposure to levonorgestrel during pregnancy; closely follow pregnancy
• Female and male reproductive potential
• The probability to conceive within 12 months after the removal of the Intrauterine system was reported to be approximately 77%
• 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 other LNG-releasing IUSs, 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 an LNG-releasing IUS