Levonorgestrel intrauterine device: Drug information

(For additional information see "Levonorgestrel intrauterine device: Patient drug information" and see "Levonorgestrel intrauterine device: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Kyleena;
Liletta (52 MG);
Mirena (52 MG);
Skyla

Brand Names: Canada

Kyleena;
Mirena

Pharmacologic Category

Contraceptive;
Progestin

Dosing: Adult

Abnormal uterine bleeding, nonacute

Abnormal uterine bleeding, nonacute (52 mg devices: Mirena, Liletta): Note: Indicated for nonacute abnormal uterine bleeding (ie, heavy menstrual bleeding); not indicated for management of acute abnormal bleeding (ie, excessively heavy or prolonged bleeding that requires urgent evaluation).

Initiation of therapy: For patients not currently using a hormonal contraceptive or intrauterine contraception, insert the IUD into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after onset of menses, use a barrier method of contraception for 7 days.

Continuation of therapy: Menstrual suppression may attenuate prior to recommended durations for contraception, requiring more frequent replacement of the device (Ref). When it is time to replace IUD, remove and replace with a new device immediately, or at any time during menstrual cycle as follows, provided the patient is not pregnant:

Mirena: In general, replace by the end of 5 years for nonacute abnormal uterine bleeding. Initially releases levonorgestrel 21 mcg/day, then rate subsequently decreases to ~11 mcg/day after 5 years and to 7 mcg/day after 8 years. If bleeding is controlled and contraception is still desired, may leave in place for up to 8 years.

Liletta: In general, replace by the end of 5 years for nonacute abnormal uterine bleeding. Initially releases levonorgestrel 20 mcg/day, then rate subsequently decreases to ~6.5 mcg/day after 8 years. If bleeding is controlled and contraception is still desired, may leave in place up to 8 years.

Note: For instruction on switching from a different contraceptive and use after childbirth, abortion, or miscarriage, refer to dosing for "Contraception."

Contraception

Contraception:

Initiation of therapy: In patients not currently using a hormonal contraceptive or intrauterine contraception, insert IUD into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, use a barrier method of contraception for 7 days unless the patient abstains from sexual intercourse.

Continuation of therapy: When it is time to replace IUD, remove and replace immediately or at any time during menstrual cycle as follows, as long as the patient is not pregnant:

Kyleena: Replace by the end of 5 years. Initially releases levonorgestrel ~17.5 mcg/day after 24 days, then rate subsequently decreases; the average release rate over 5 years is levonorgestrel ~9 mcg/day. Do not leave device in place for >5 years.

Liletta: Replace by the end of 8 years. Initially releases levonorgestrel ~20 mcg/day, then rate subsequently decreases; the average release rate over 8 years is levonorgestrel ~13.5 mcg/day. Do not leave in place for >8 years.

Mirena: Replace by the end of 8 years. Initially releases levonorgestrel 21 mcg/day, then rate subsequently decreases to ~11 mcg/day after 5 years and 7 mcg/day after 8 years. Do not leave device in place for >8 years.

Skyla: Replace by the end of 3 years. Initially releases levonorgestrel ~14 mcg/day after 24 days, then rate subsequently decreases; mean release rate over 3 years is levonorgestrel ~6 mcg/day. Do not leave device in place for >3 years.

**Patients Switching from a Different Contraceptive to Levonorgestrel IUD**
Current method	Instructions for switching to levonorgestrel IUD
^a When switching from a copper IUD, if sexual intercourse occurred after the start of the current cycle, and it has been >5 days since bleeding began, consider administering an emergency contraceptive (CDC [Curtis 2016a]).
Hormonal contraceptive (oral, transdermal, vaginal)	Insert levonorgestrel IUD at any time, including hormone-free interval of the previous method. If inserted during active use of the previous method, continue previous method for 7 days after insertion or until the end of the current treatment cycle. If using continuous hormonal contraception, continue previous method for 7 days after insertion.
Injectable progestin	Insert levonorgestrel IUD at any time. If inserted >13 weeks after the last injection, use a barrier method of contraception for 7 days.
Implant or another intrauterine system (IUS)^a	Insert levonorgestrel IUD on the same day the implant or IUS is removed, any time during the menstrual cycle.

Switching from levonorgestrel IUD to a different contraceptive: If the patient wishes to change to a different method of birth control, remove IUD during the first 7 days of menstrual cycle and begin the new therapy. If the IUD is not removed during the first 7 days of menstruation (or if the patient has irregular menstrual cycles or amenorrhea), start the new method at least 7 days prior to IUD removal, otherwise, use a back-up barrier contraceptive for 7 days after the IUD is removed, unless the patient abstains from vaginal intercourse.

**Use of Levonorgestrel IUD After Childbirth, Abortion, or Miscarriage**
^aProduct labeling recommends insertion following removal of the placenta, or waiting at least 6 weeks following delivery, or until the uterus is fully involuted. According to evidence-based guidelines, insertion postpartum (immediate insertion within 10 minutes of placental delivery or interval insertion during the 6-week postpartum period) or following an abortion are safe despite a higher risk of expulsion immediately postpartum or following a second trimester abortion and may be offered regardless of breastfeeding status to help prevent rapid repeat and unintended pregnancies (ACOG 2017; CDC [Curtis 2016b]).
^b Back up contraception is needed for 7 days unless IUD is placed at the time of surgical abortion. Do not administer immediately following a septic abortion (CDC [Curtis 2016a]).
Use after childbirth (immediate)	Insert levonorgestrel IUD after removal of the placenta; backup contraception is not needed.^a
Use after childbirth (interval insertion following complete involution of the uterus)	Do not insert levonorgestrel IUD <6 weeks after childbirth or if the uterus is not fully involuted.^a Insert at any time if it is determined that the patient is not pregnant. If menstruation has not yet resumed, consider the possibility of ovulation and conception occurring prior to IUD insertion. Back-up contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, use a barrier method of contraception for 7 days unless the patient abstains from sexual intercourse. The risk of perforation is increased in lactating patients.
Use after first trimester abortion or miscarriage^b	Insert levonorgestrel IUD immediately after a first-trimester abortion or miscarriage.
Use after second trimester abortion or miscarriage^b	Refer to instructions for use after childbirth.

Dysmenorrhea

Dysmenorrhea (off-label use): 52 mg device: Refer to dosing for "Contraception" (Ref).

Endometrial hyperplasia, treatment

Endometrial hyperplasia, treatment (off-label use): 52 mg device: Insert into the intrauterine cavity for hyperplasia without atypia or atypical endometrial hyperplasia/endometrial intraepithelial neoplasia. IUDs that contain levonorgestrel 52 mg in a reservoir initially release ~20 mcg/day then progressively decrease to ~10 mcg/day after 5 years. Replace after 5 years; however, the optimal duration of treatment is not known (Ref).

Estrogen therapy-associated endometrial hyperplasia, prevention

Estrogen therapy-associated endometrial hyperplasia, prevention (off-label use) (alternative agent):

Note: Based on data in patients who are peri- and postmenopausal; may be considered as an alternative for prevention of endometrial hyperplasia in patients with a uterus receiving estrogen therapy (eg, for vasomotor symptoms associated with menopause or secondary amenorrhea) but who are unable to tolerate oral progestogen (ie, a natural progesterone or synthetic progestin) regimens, particularly if patients desire or need contraception and/or treatment for heavy menstrual bleeding (Ref).

All devices: Confirm no possibility of pregnancy. Insert into the intrauterine cavity. In patients with menstrual cycles, may insert at any time. Discontinue when estrogen therapy is discontinued, unless also being used for contraception. Refer also to dosing for "Contraception." Note: Limited data are available with an IUD that released levonorgestrel 20 mcg/day for up to 5 years; however, levonorgestrel 14 mcg/day for up to 3 years has also been studied (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use of the intrauterine device is contraindicated with active hepatic disease or hepatic tumor.

Dosing: Older Adult

Not indicated for use in patients who are postmenopausal.

Dosing: Pediatric

(For additional information see "Levonorgestrel intrauterine device: Pediatric drug information")

Contraception or heavy menstrual bleeding

Contraception (Kyleena, Liletta, Mirena, Skyla ) or heavy menstrual bleeding (Mirena ):

Postmenarche patients: Intrauterine device (IUD):

Initiation of therapy: In patients not currently using a hormonal contraceptive or intrauterine contraception, the IUD may be inserted into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Backup contraception is not needed if insertion is within 7 days of onset of menstruation. If insertion occurs >7 days after menstrual bleeding started, a barrier method of contraception must be used for 7 days unless the patient abstains from sexual intercourse.

Continuation of therapy: Duration of action is product-specific. When it is time to replace, the dated IUD is removed and replaced as follows with a new device immediately, and at any time during menstrual cycle as long as the patient is not pregnant:

Liletta: Replace by the end of 8 years. Initially releases levonorgestrel 20 mcg/day, then rate subsequently decreases; the average release rate over 8 years is levonorgestrel ~13.5 mcg/day. Do not leave in place for >8 years.

**Patients Switching from a Different Contraceptive to Levonorgestrel IUD**
Current Method	Instructions for Switching to Levonorgestrel IUD
^a When switching from a copper IUD, if sexual intercourse occurred after the start of the current cycle, and it has been >5 days since bleeding began, consider administering an emergency contraceptive (CDC [Curtis 2016a]).
Hormonal contraceptive (oral, transdermal, vaginal)	Levonorgestrel IUD may be inserted anytime, including hormone-free interval of the previous method. If inserted during active use of the previous method, continue previous method for 7 days after insertion or until the end of the current treatment cycle. If using continuous hormonal contraception, continue previous method for 7 days after insertion.
Injectable progestin	Levonorgestrel IUD may be inserted at any time. If inserted >13 weeks after the last injection, a barrier method of contraception should also be used for 7 days.
Implant or another intrauterine system (IUS)^a	Levonorgestrel IUD may be inserted on the same day the implant or IUS is removed, any time during the menstrual cycle.

Switching from levonorgestrel IUD to a different contraceptive: If the patient wishes to change to a different method of birth control, may remove the device during the first 7 days of menstrual cycle and begin the new therapy. If the device is not removed during the first 7 days of menstruation (or if the patient has irregular menstrual cycles or amenorrhea) and wants to start a different method of birth control, start the new method at least 7 days prior to device removal, otherwise, a backup barrier contraceptive should be used for 7 days after the device is removed unless the patient abstains from vaginal intercourse.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Postmenarche patients: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use of the intrauterine device is contraindicated with active hepatic disease or hepatic tumor.

Adverse Reactions (Significant): Considerations

Bleeding irregularities

Levonorgestrel intrauterine device (IUD) is associated with changes in gynecological bleeding patterns, including increased number of bleeding/spotting days, irregular bleeding patterns, oligomenorrhea, and amenorrhea. Rates of frequent or prolonged bleeding rapidly decline with continued use (Ref). Menstrual blood loss can decrease by 96% after 1 year of use (Ref). Approximately 20% of women will continue to experience bleeding irregularities with continued use (Ref). Bleeding irregularities have been associated with dissatisfaction and discontinuation in some users (Ref).

Mechanism: Dose-related; in addition to impacting ovulation, bleeding irregularities may be due to changes in the endometrium due to sustained progestogen exposure, decrease in steroid hormone receptors, and lack of local estrogen exposure (Ref).

Onset: Varied; the first 3 to 6 months of use are generally most associated with bleeding irregularities (Ref). Twenty-six percent of users reported frequent bleeding in the first 90 days of use versus <10% in the subsequent 90 days (Ref).

Risk factors:

• Products containing higher doses of levonorgestrel are associated with more amenorrhea (Ref)

• Self-reported duration of menstrual flow of <7 days is predictive of amenorrhea at 12 months (Ref)

• Duration of menses <5 days and absence of heavy menstrual bleeding at baseline is predicative of oligomenorrhea at 12 months (Ref)

Device expulsion

Device expulsion (ie, female birth control expulsion from genital tract) is the passage of the intrauterine device (IUD) either partially or completely through the external cervical os (Ref). Expulsion may be asymptomatic and discovered by a patient when the threads are shorter than normal, uneven, or can no longer be felt (Ref). Expulsion may also be associated with pain, bleeding, or a change in bleeding patterns (such as increased bleeding) (Ref).

Onset: Varied; highest rate of expulsion is during the first year after placement of device (Ref).

Risk factors:

• Immediate/early (<4 weeks) postpartum placement (Ref)

• Immediate postabortion placement (Ref)

• Insertion into uterus <5.5 cm

• Insertion into uterus not completely involuted at the time of insertion

• Parous females (Ref)

• Vaginal delivery (Ref)

• Not breastfeeding at time of insertion

• History of heavy menstrual bleeding

• Greater than normal BMI at time of insertion

Ectopic pregnancy

Rates of ectopic pregnancy (EP) with levonorgestrel intrauterine device (IUD) use are rare and lower than the general population (Ref). However, 25% to 50% of pregnancies that occur while a device is in place are likely to be ectopic with an associated risk of rupture and high morbidity (fertility loss, pregnancy loss, septic abortion) and mortality (Ref).

Mechanism: Unknown; increased EP risk may be due to failure of the device (Ref). Progesterone may facilitate ciliary dysfunction and impair smooth muscle contraction within the fallopian tube, resulting in tubal retention and subsequent implantation (Ref). If the device migrates, an inflammatory reaction may occur, interfering with tubal function (Ref).

Onset: Varied; risk may be higher during the first year of use (Ref); however, presentation has occurred after various durations of therapy (Ref). Case reports describe diagnosis after several days of vaginal bleeding, vomiting, lower abdominal pain, loose stools, and abdominal fullness worsening over several days (Ref).

Risk factors:

• Lower IUD dose (Ref)

• First year of use (Ref)

• Device migration; however, in one case report, EP occurred with a correctly positioned device (Ref)

• Leaving device in place longer than indicated (Ref)

• History of EP

• Tubal surgery

• Pelvic infection

Perforation/embedded device

Penetration or embedment into the uterine wall or cervix is uncommon but is an important risk to consider with intrauterine device (IUD) use (Ref). Data from the FDA mandated study APEX-IUD (Association of Uterine Perforation and Expulsion of Intrauterine Device Study) approximates the risk at 1 to 2 perforations per 1,000 insertions (Ref). Uterine perforation may be asymptomatic and not discovered for months or years after insertion (Ref). Perforation may reduce contraceptive efficacy and result in pregnancy. Delayed detection or removal in cases of perforation may result in migration of IUD outside of uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses, and erosion of adjacent viscera.

Mechanism: Complete perforation generally occurs during insertion when the IUD is forced into or through the uterine wall infiltrating all uterine layers (endometrium, myometrium, and serosa) (Ref). Partial perforation or embedment is less common but takes place when the IUD penetrates the uterine wall and remains in the myometrium (Ref). While most perforations occur during insertion, secondary perforations/embedment may occur via gradual erosion through the myometrium (Ref). Hence, a partial perforation may eventually become a complete perforation (Ref). Uterine contractions may be a factor contributing to perforations and transmural migration (Ref).

Onset: Varied; most cases are not recognized at the time of insertion. Discovery of penetration/embedment may be months to years after insertion of IUD (Ref). One case was discovered 1 month after insertion by routine ultrasound (Ref).

Risk factors:

• Postpartum placement up to 36 weeks (Ref)

• Insertion into uterus <5.5 cm

• Insertion into uterus when fixed, retroverted, or not completely involuted (Ref)

• Breastfeeding at time of insertion (Ref)

• Amenorrheic at time of insertion (Ref)

• Insertion by a less experienced clinician (Ref)

• Lower parity (Ref)

• Higher number of previous abortions (Ref)

• Altered myometrial integrity (eg, postmenopausal, prolonged concurrent steroid use) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adolescents and adults.

>10%:

Dermatologic: Acne vulgaris (7% to 15%)

Endocrine & metabolic: Amenorrhea (≤40%; increases with duration of treatment)

Gastrointestinal: Abdominal pain (≤23%)

Genitourinary: Bacterial vaginosis (19%), gynecological bleeding (including decreased, increased, heavy, irregular, prolonged, unscheduled, frequent and infrequent uterine bleeding), ovarian cyst (1% to 22%), pelvic pain (≤23%), vaginal discharge (4% to 15%), vaginal mycosis (19%), vulvovaginitis (11% to 24%)

Nervous system: Headache (≤16%), migraine (≤16%)

1% to 10%:

Dermatologic: Alopecia (1%), seborrhea (1% to 2%)

Endocrine & metabolic: Hirsutism (<5%), weight gain (6%)

Gastrointestinal: Abdominal distress, nausea, vomiting

Genitourinary: Bacterial reproductive infection (1% to 4%), breast tenderness (including discomfort: ≤10%), dysmenorrhea (6% to 9%), dyspareunia (9%), endometritis (≤2%), female birth control expulsion from genital tract (3% to 9%; partial and complete), mastalgia (≤10%), pelvic inflammatory disease (<5%), uterine spasm (2%)

Nervous system: Anxiety (9%), depressed mood (≤6%), depression (≤8%), mood changes (6%)

Neuromuscular & skeletal: Back pain (6% to 8%)

<1%: Genitourinary: Ectopic pregnancy, uterine perforation

Postmarketing:

Cardiovascular: Arterial thromboembolism, deep vein thrombosis, increased blood pressure, pulmonary embolism

Genitourinary: Malignant neoplasm of breast

Hypersensitivity: Angioedema

Infection: Sepsis (including Group A streptococcal sepsis) (Balayla 2019), severe infection

Nervous system: Cerebrovascular accident

Miscellaneous: Breakage of IUD

Contraindications

Hypersensitivity to levonorgestrel or any component of the formulation; pregnancy or suspected pregnancy; postcoital contraception; congenital or acquired uterine anomaly, including leiomyomas that distort the uterine cavity and would be incompatible with correct IUD placement; acute pelvic inflammatory disease or history of pelvic inflammatory disease (unless there has been a subsequent intrauterine pregnancy); postpartum endometritis or infected abortion within past 3 months; known or suspected uterine or cervical malignancy; untreated acute cervicitis or vaginitis (including bacterial vaginosis, known chlamydial or gonococcal cervical infection) or other lower genital tract infections until infection is controlled; conditions which increase susceptibility to pelvic infections; unremoved IUD; uterine bleeding of unknown etiology; acute hepatic disease or hepatic tumors (benign or malignant); current or history of known or suspected breast cancer or other hormone-sensitive cancer.

Canadian labeling: Additional contraindications (not in US labeling): Bacterial endocarditis; recent trophoblastic disease while human chorionic gonadotropin (hCG) hormone levels are elevated; cervical dysplasia; known immunodeficiency or hematologic malignancy (Mirena)

Warnings/Precautions

Concerns related to adverse effects:

• Bradycardia/syncope: Bradycardia or syncope may occur during insertion or removal of the IUD; use with caution in patients predisposed to these conditions.

• Pelvic inflammatory disease: An increased incidence of group A streptococcal sepsis, pelvic inflammatory disease (PID) or endometritis (may be asymptomatic), and actinomycosis has been reported with use. Using aseptic technique during insertion is essential to minimizing the risk of serious infections. PID occurs more frequently within the first year and most often within the first month after insertion; risk is increased with multiple sexual partners. Patients with a history of PID or endometritis are at increased risk. If PID is diagnosed, treat according to current guidelines and reassess in 48 to 72 hours. If there is no clinical improvement, continue antibiotics and consider removal of device (CDC [Curtis 2016a]). Remove the device in patients with symptomatic actinomycosis and treat with appropriate antibiotics. Remove IUD in cases of recurrent endometritis or PID, or if an acute pelvic infection is severe or does not respond to treatment.

• Seizure: Insertion or removal may be associated with seizure, especially in patients predisposed to seizures.

Disease-related concerns:

• Cervical or endometrial cancer: Do not use an IUD for pregnancy prevention in patients diagnosed with cervical or endometrial cancer prior to IUD insertion (may have an increased risk of bleeding or infection when the device is inserted). Patients diagnosed after insertion of an IUD may continue; however, the IUD will most likely need to be removed during treatment (CDC [Curtis 2016b]). If significant bleeding irregularities occur with prolonged use, conduct diagnostic tests to assess possible endometrial pathology (polyps or cancer).

• Depression: Use with caution in patients with depression; may be more susceptible to recurrence of depressive episodes; consider removal of IUD for serious recurrence. Depression is not a contraindication to use of the IUD (CDC [Curtis 2016b]).

• Gestational trophoblastic disease: Patients with gestational trophoblastic disease are at increased risk of adverse events if pregnancy occurs; use of the levonorgestrel IUD may be appropriate for prevention of pregnancy in some situations with close medical supervision. However, do not initiate therapy with a levonorgestrel IUD in patients with persistently elevated beta-hCG concentrations or malignant disease with evidence or suspicion of intrauterine disease due to risks of infection, hemorrhage, or perforation. Consider benefits of effective contraception versus risks of continuation/removal in patients who have a levonorgestrel IUD already in place (CDC [Curtis 2016b]).

• Sepsis: Do not insert levonorgestrel IUD in patients with postpartum sepsis or immediately following a septic abortion (CDC [Curtis 2016b]).

• Sexually transmitted infection: Do not initiate levonorgestrel IUD in patients with purulent cervicitis, chlamydial, or gonococcal infection. The IUD does not need to be removed if diagnosis occurs with the IUD in place, as long as there is treatment with appropriate antibiotics, symptoms resolve, and consideration is given to personal risk factors and patient preference (CDC [Curtis 2016a]; CDC [Curtis 2016b]).

• Tuberculosis: Insert in patients with nonpelvic tuberculosis; do not initiate treatment in cases of pelvic infection and consider removal when pelvic infection occurs with the IUD in place (CDC [Curtis 2016b]).

Special populations:

• Body weight: Clinical trials did not exclude patients based on BMI (CDC [Curtis 2016a]). A greater than normal BMI may increase the risk of expulsion.

• Smoking: The risk of cardiovascular side effects increases in patients using estrogen-containing combined hormonal contraceptives and who smoke cigarettes, especially those who are >35 years of age. This risk relative to progestin-only contraceptives has not been established. Advise patients who take combination hormonal contraceptives not to smoke. Smoking is not a contraindication to use of the IUD (CDC [Curtis 2016b]).

Dosage form specific issues:

• Consent form: Some products provide a consent form; keep a copy of the form and lot number with the patient's medical record.

• MRI: Only under specific conditions may an IUD be scanned safely by MRI (refer to manufacturer's labeling for requirements). Image quality may also be impaired if area of interest is relatively close to the device.

Other warnings/precautions:

• Appropriate use: IUD: Insert by a trained health care provider. Insertion and removal may be associated with pain and/or bleeding; consider analgesics prior to insertion. Removal of the device may be necessary for the following reasons: pelvic infection or disease, endometritis, symptomatic genital actinomycosis, uterine or cervical cancer, uterine or cervical perforation, partial expulsion, and pregnancy. Use with caution if any of the following conditions exist and consider removal if any of them arise during use: Coagulopathy or are receiving anticoagulants; marked increase of blood pressure; severe arterial disease, such as stroke or MI; exceptionally severe headache; and migraine, focal migraine with asymmetrical visual loss, or other symptoms indicating transient cerebral ischemia. In addition, consider removal if jaundice occurs during use.

• HIV infection protection: Intrauterine devices do not protect against HIV infection or other sexually transmitted diseases (CDC [Curtis 2016b]).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Intrauterine Device, Intrauterine:

Kyleena: 19.5 mg

Liletta (52 MG): 20.1 mcg/day

Mirena (52 MG): 20 mcg/day

Skyla: 13.5 mg

Generic Equivalent Available: US

Pricing: US

Intrauterine Device (Kyleena Intrauterine)

19.5 mg (per each): $1,388.15

Intrauterine Device (Liletta (52 MG) Intrauterine)

20.1 mcg/day (per each): $1,064.83

Intrauterine Device (Mirena (52 MG) Intrauterine)

20 mcg/day (per each): $1,388.15

Intrauterine Device (Skyla Intrauterine)

13.5 mg (per each): $1,155.86

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Intrauterine Device, Intrauterine:

Kyleena: 19.5 mg

Mirena: 52 mg

Administration: Adult

To be inserted into the uterine cavity. Consider administering analgesics or cervical anesthetic prior to insertion. Insert into the uterine cavity to the recommended depth with the provided insertion device; do not force into the uterus. If necessary, dilate the cervical canal and consider using a paracervical block. Transvaginal ultrasound may be used to check proper placement. Remove if not positioned properly and insert a new IUD; do not reinsert removed IUD. Exclude uterine perforation if exceptional pain or bleeding occurs after insertion. Ensure device is intact after removal. Check expiration of IUD prior to insertion. Use of the provided inserter and directions for insertion are different for immediate insertion after childbirth or second-trimester abortion, or miscarriage. Refer to manufacturer's labeling for additional administration instructions.

Because testosterone may cause vaginal atrophy, consider pretreating with vaginal estrogen for 2 weeks prior to insertion to patients on gender-affirming testosterone therapy (Ref).

Dysmenorrhea (off-label use): 52 mg device: Consider placing IUD during diagnostic laparoscopy to minimize pain of insertion for patients undergoing this procedure (Ref).

In case of breakage or embedment of IUD in the myometrium, analgesia, paracervical anesthesia, cervical dilation, alligator forceps, or hysteroscopy may be used to aid in removal.

Administration: Pediatric

Intrauterine device (IUD): To be inserted into the uterine cavity by a health care professional. Consider administering analgesics or cervical anesthetic prior to insertion. Insert into the uterine cavity to the recommended depth with the provided insertion device; should not be forced into the uterus. If necessary, dilate the cervical canal and consider using a paracervical block. Transvaginal ultrasound may be used to check proper placement. Remove if not positioned properly and insert a new IUD; do not reinsert removed IUD. Exclude uterine perforation if exceptional pain or bleeding occurs after insertion. Ensure device is intact after removal. Check expiration of IUD prior to insertion. Refer to manufacturer's labeling for additional administration instructions. For patients on gender-affirming testosterone therapy, consider pretreating with vaginal estrogen for 2 weeks prior to insertion because testosterone may cause vaginal atrophy (Ref). In case of breakage or embedment of IUD in the myometrium, analgesia, paracervical anesthesia, cervical dilation, alligator forceps, or hysteroscopy may be used to aid in removal.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Use: Labeled Indications

Abnormal uterine bleeding, nonacute (52 mg devices: Mirena, Liletta): Treatment of abnormal uterine bleeding (ie, heavy menstrual bleeding) in patients who also choose to use an IUD for contraception.

Contraception: Prevention of pregnancy (up to 3 years [Skyla], 5 years [Kyleena], or 8 years [Liletta, Mirena]).

Limitations of use: For use in patients who may become pregnant; not for use prior to menarche or post menopause.

Use: Off-Label: Adult

Dysmenorrhea; Emergency contraception; Endometrial hyperplasia, treatment; Estrogen therapy-associated endometrial hyperplasia, prevention; Menstrual suppression

Medication Safety Issues

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Chlorprothixene: Progestins may enhance the adverse/toxic effect of Chlorprothixene. Progestins may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May diminish the therapeutic effect of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease the serum concentration of Levonorgestrel (IUD). Risk C: Monitor therapy

MetyraPONE: Progestins may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider therapy modification

Ulipristal: May diminish the therapeutic effect of Progestins. Progestins may diminish the therapeutic effect of Ulipristal. Risk X: Avoid combination

Reproductive Considerations

Evaluate pregnancy status prior to insertion.

Insert into the uterine cavity at any time during the menstrual cycle once it is determined that the patient is not pregnant. Insert immediately following a first trimester-induced or spontaneous abortion. Following pregnancy or a second trimester induced or spontaneous abortion, insert following removal of the placenta, or do not insert for at least 6 weeks or until involution of the uterus is complete. Insertion postpartum (immediate insertion within 10 minutes of placental delivery or interval insertion during the 6-week postpartum period) or following an abortion are safe despite a higher risk of expulsion immediately postpartum and following a second trimester abortion; offer regardless of breastfeeding status to help prevent rapid repeat and unintended pregnancies (ACOG 2017; CDC [Curtis 2016b]).

All available forms of contraception, including the levonorgestrel IUD, can be considered for patients on gender-affirming testosterone therapy after evaluating the appropriateness of the method based on the patient's preferences and medical conditions (Bonnington 2020; Krempasky 2020).

When treating patients with secondary amenorrhea (hypoestrogenism) due to primary ovarian failure, consider use of the levonorgestrel IUD in place of an oral progestogen for patients not wishing to become pregnant (ACOG 2017).

Following removal of the device, ~71% to 85% of patients who wished to conceive became pregnant within 12 months.

Pregnancy Considerations

Use during pregnancy or a suspected pregnancy is contraindicated.

Patients who become pregnant with an IUD in place risk spontaneous or septic abortion; septicemia, septic shock, and death may occur. In addition, the likelihood of ectopic pregnancy is increased; miscarriage, sepsis, premature labor, and premature delivery may occur if pregnancy is continued. Removal of the device is recommended if strings are visible or removal can be done safely from the cervical canal. However, removal or manipulation of IUD or probing of the uterus may result in pregnancy loss. Consider use of an ultrasound to determine location of IUD prior to removal (CDC [Curtis 2016a]).

Virilization of the female fetus has been observed following exposure to the levonorgestrel IUD.

Breastfeeding Considerations

Levonorgestrel is present in breast milk.

Two studies evaluated levonorgestrel breast milk concentrations following IUD insertion among patients 4 to 6 weeks postpartum (Heikkilä 1982; Shikary 1987). In 1 study, there was no correlation between dose and maternal serum or milk concentrations, although the authors calculated the infants received a relative dose of 1.2% of the maternal dose (Heikkilä 1982). In both studies, the milk/plasma ratio increased over time during the 4- and 12-week study periods (Heikkilä 1982; Shikary 1987). Levonorgestrel was also detected in the serum of breastfeeding infants (Shikary 1987).

Concentrations of levonorgestrel and fat content in breast milk are similar 4 to 8 weeks after initial IUD insertion regardless if placement occurs immediately after delivery or at the first postpartum visit (4 to 8 weeks after delivery) (Hopelian 2021). The onset of lactogenesis and the duration of breastfeeding were not found to be influenced by the time of initial IUD placement (immediately after delivery or 4 to 8 weeks postpartum) (Turok 2017).

In general, no adverse effects on the growth or development if the infant have been observed. Isolated cases of decreased milk production have been reported.

Maternal plasma concentrations of levonorgestrel are dependent upon sex hormone binding globulin capacity, which is influenced by concomitant administration with estrogen or the postpartum status (Orme 1983). Risk of perforation with IUD is increased in patients who are lactating. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the patient.

Following pregnancy, insert following removal of the placenta, or do not insert for at least 6 weeks postpartum or until involution of the uterus is complete. Insert immediately postpartum in patients who are breastfeeding, including patients who had a cesarean delivery. Risk of infection is not increased; risk of expulsion may be increased. Consider risk of expulsion along with the need for effective contraception and patient access to placement at a later time (CDC [Curtis 2016b]).

Monitoring Parameters

Prior to insertion: Confirm no possibility of pregnancy; bimanual examination and cervical inspection; weight (optional; BMI at baseline may be helpful to monitor changes during therapy); STI screen (unless already screened according to CDC STD treatment guidelines) (CDC [Curtis 2016a]). Evaluate any unexplained vaginal bleeding; exclude endometrial polyps or cancers (CDC [Curtis 2016b]). Complete medical and social history, which may determine conditions influencing an IUD use for contraception.

Following insertion: Transvaginal ultrasound may be used to check placement. Assess changes in health status (including medications) at routine follow-up visits (CDC [Curtis 2016a]). Re-examine following insertion (4 to 6 weeks) and then yearly or more frequently if necessary. Threads should be visible; if length of thread has changed, device may have become displaced, broken, perforated the uterus, or expelled. If the IUD is not found in the uterus, consider further testing to confirm expulsion (eg, sonography, X-ray). Reassess pregnancy status if menstruation does not occur within 6 weeks of previous menstrual period. Monitor for significant changes in menstrual bleeding during prolonged use, Pap smear, BP, serum glucose in patients with diabetes. Evaluate patients presenting with lower abdominal pain for ectopic pregnancy (especially in association with missed periods) and ovarian cysts. Monitor for signs of infection. Monitor for signs/symptoms of thromboembolism in patients who require surgery with prolonged immobilization.

Endometrial hyperplasia, treatment (off-label use): Endometrial sampling every 3 to 6 months, although most appropriate frequency has not been determined (ACOG 2023; SOGC [Auclair 2019]).

Reference Range

Kyleena: Plasma concentrations range from 175 ± 74 pg/mL (7 days following insertion) to 90 ± 35 pg/mL (after 5 years).

Liletta: Plasma concentrations range from a peak of 252 ± 123 pg/mL (7 days following insertion) to 88 ± 37 pg/mL (after 8 years).

Mirena: Plasma concentrations range from 150 to 200 pg/mL.

Skyla: Plasma concentrations range from a peak of 192 pg/mL (2 days following insertion) to 59 to 61 pg/mL (after 3 years).

Mechanism of Action

Pregnancy may be prevented through several mechanisms: Thickening of cervical mucus, which inhibits sperm passage through the uterus; inhibition of sperm survival; alteration of the endometrium. Inhibition of ovulation may also occur in some patients.

Pharmacokinetics (Adult Data Unless Noted)

Duration: Prevention of pregnancy: Kyleena: Up to 5 years; Liletta, Mirena: Up to 8 years; Skyla: Up to 3 years.

Distribution: V_d: ~1.8 L/kg.

Protein binding: Highly bound to albumin (~50%) and sex hormone-binding globulin (~47%) (Fotherby 1995).

Metabolism: Hepatic via CYP3A4; forms inactive metabolites.

Excretion: Urine (~45%); feces (~32%).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Mirena;
(AR) Argentina: Blusiri | Kyleena | Mirena;
(AT) Austria: Jaydess | Kyleena | Levosert | Levosert one | Mirena;
(AU) Australia: Kyleena | Mirena;
(BE) Belgium: Jaydess | Kyleena | Levonortis | Levosert | Mirena;
(BG) Bulgaria: Jaydess | Levosert | Mirena;
(BR) Brazil: Kyleena | Mirena;
(CH) Switzerland: Jaydess | Kyleena | Levosert | Mirena;
(CI) Côte d'Ivoire: Mirena;
(CL) Chile: Asertia | Jaydess | Kyleena | Levosert 1 | Mirena;
(CN) China: Mirena;
(CO) Colombia: Jaydess | Kyleena | Mirena;
(CZ) Czech Republic: Jaydess | Kyleena | Levosert shi | Mirena;
(DE) Germany: Jaydess | Kyleena | Levosert | Mirena;
(DO) Dominican Republic: Mirena;
(EC) Ecuador: Asertia | Jaydess | Mirena;
(EE) Estonia: Donasert | Fleree | Kyleena | Mirena | Mirena ess-steem;
(ES) Spain: Jaydess | Kyleena | Levosert | Levosert one | Mirena;
(ET) Ethiopia: Eloira | Mirena;
(FI) Finland: Jaydess | Kyleena | Mirena;
(FR) France: Donasert | Jaydess | Kyleena | Mirena;
(GB) United Kingdom: Benilexa one handed | Jaydess | Kyleena | Levosert | Mirena;
(GR) Greece: Mirena;
(HK) Hong Kong: Mirena;
(HR) Croatia: Mirena;
(HU) Hungary: Jaydess | Levosert | Mirena;
(IE) Ireland: Jaydess | Kyleena | Mirena;
(IL) Israel: Mirena;
(IN) India: Emily | Erinna | Levodiva | Mirena;
(IT) Italy: Benilexa | Jaydess | Kyleena | Mirena;
(KE) Kenya: Lng ius | Mirena;
(KR) Korea, Republic of: Jaydess | Kyleena | Mirena;
(KW) Kuwait: Mirena;
(LB) Lebanon: Mirena;
(LT) Lithuania: Fleree | Kyleena | Levosert | Levosert single handed inserter | Mirena;
(LU) Luxembourg: Jaydess | Levonortis | Levosert | Mirena;
(LV) Latvia: Fleree | Kyleena | Levosert | Levosert shi | Mirena;
(MA) Morocco: Mirena;
(MX) Mexico: Jaydess | Kyleena | Miacare | Mirena;
(MY) Malaysia: Mirena;
(NG) Nigeria: Eloira | Mirena;
(NL) Netherlands: Kyleena | Levosert | Mirena;
(NO) Norway: Jaydess | Kyleena | Levonova | Levosert | Mirena;
(NZ) New Zealand: Jaydess | Mirena l;
(PE) Peru: Jaydess | Mirena;
(PH) Philippines: Mirena;
(PK) Pakistan: Mirena;
(PL) Poland: Jaydess | Kyleena | Levosert | Mirena;
(PR) Puerto Rico: Kyleena | Liletta | Mirena | Skyla;
(PT) Portugal: Jaydess | Kyleena | Levosert | Levosert one | Mirena;
(PY) Paraguay: Mirena;
(QA) Qatar: Mirena (52 mg);
(RO) Romania: Donasert | Jaydess;
(RU) Russian Federation: Mirena;
(SE) Sweden: Jaydess | Kyleena | Levosert | Levosertone | Mirena;
(SG) Singapore: Jaydess | Mirena;
(SI) Slovenia: Jaydess | Kyleena | Levosert | Levosert shi | Mirena;
(SK) Slovakia: Jaydess | Levosert | Levosert shi | Mirena;
(TH) Thailand: Mirena;
(TN) Tunisia: Mirena;
(TR) Turkey: Mirena;
(TW) Taiwan: Jaydess | Mirena;
(UA) Ukraine: Jaydess | Mirena;
(UG) Uganda: Mirena;
(UY) Uruguay: Jaydess | Kyleena | Mirena;
(VE) Venezuela, Bolivarian Republic of: Eloira | Mirena;
(ZA) South Africa: Kyleena | Mirena

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Levonorgestrel intrauterine device: Drug information