Dosing and uses of Mirena, Skyla (levonorgestrel intrauterine)
Adult dosage forms and strengths
levonorgestrel-releasing intrauterine system
- 13.5mg/device (Skyla)
- 19.5mg/device (Kyleena)
- 20mcg/24hr (Mirena)
- 52mg/device (Liletta)
Contraception
Mirena
- Initial levonorgestrel release rate is 20 mcg/day; rate reduced by 50% after 5 years
- May remove and replace with a new unit anytime during menstrual cycle
- Must be removed or replaced by 5 years following insertion
Skyla
- 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 menstrual cycle
- Must be removed or replaced by 3 years following insertion
Liletta
- Levonorgestrel release rate is 18.6 mcg/day initially; release rate decreases to 16.3 mcg/day at 1 year, 14.3 mcg/day at 2 years, and 12.6 mcg/day at 3 years after insertion
- May remove and replace with a new unit anytime during menstrual cycle
- Must be removed or replaced by the end of the third year following insertion
Kyleena
- 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 menstrual cycle
- Must be removed or replaced by 5 years following insertion
Menorrhagia
Indicated for heavy menstrual bleeding for women who choose to use intrauterine contraception (Mirena only)
Insert into uterine cavity within 7 days of mensturation onset or immediately after first trimester abortion
Mirena: Initial levonorgestrel release rate is 20 mcg/day; rate reduced by 50% after 5 years; must be removed or replaced after 5 years
Dosing Considerations
Insert within 7 days of onset of menses or immediately after first trimester abortion
Re-examine and evaluate patient 4-6 weeks after insertion; then yearly or more often if indicated
Switching to Different Contraceptive
Regular menstrual cycle: Remove device during first 7 days of menstrual cycle and begin new therapy
Irregular menstrual cycle: Start new contraceptive method 7 days prior to device removaL
Pediatric dosage forms and strengths
Safety and efficacy not established
Mirena, Skyla (levonorgestrel intrauterine) adverse (side) effects
>10%
Headache (12%)
Acne (15%)
Ovarian cysts (13%)
Enlarged follicles (12%)
Amenorrhea (1-12%)
Abdominal pain (12%)
Uterine/vaginal bleeding alterations (52%)
Intermenstrual bleeding/spotting (23%)
Vulvovaginitis (20%)
Ectopic pregnancy (≤50%)
1-10%
Depression (4%)
Migraine (2%)
Alopecia (1%)
Dysmenorrhea (9%)
Menorrhagia (6%)
Breast tenderness (3-9%)
Pelvic pain (6%)
Leukorrhea (5%)
Vaginal discharge (4%)
Pelvic infection (1%)
<1%
Angioedema
Cervical perforation
Failed insertion
Sepsis
Uterine bleeding
Device breakage
Pulmonary emboli
Deep vein thrombosis and stroke
Increased blood pressure
Postmarketing Reports
Arterial thrombotic and venous thromboembolic events, including cases of pulmonary emboli, deep vein thrombosis and stroke
Warnings
Contraindications
Documented hypersensitivity; genital actinomycosis, cervicitis or vaginitis, conditions associated with increased susceptibility to infections (eg, leukemia, AIDS, IV drug abuse), history of ectopic pregnancy, postpartum endometriosis, unremoved IUD, pelvic inflammatory disease, uterine anomaly
Active or suspected carcinoma of the breast or history of breast cancer
Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease
Liver disease, liver tumors
Undiagnosed abnormal vaginal bleeding
Uncontrolled hypertension
Diabetes mellitus with vascular involvement
Jaundice with prior oral contraceptive use
Pregnancy or suspicion of pregnancy
Postpartum endometritis or infected abortion in the past 3 months
Known or suspected uterine or cervical neoplasia or unresolved, abnormal Pap smear, or progestin sensitive cancer
Conditions associated with increased susceptibility to pelvic infections
Cautions
Pregnant women whose device cannot be removed or if patient chooses not to have it removed, increases risk of miscarriage, sepsis, premature labor and premature delivery
Evaluate women for ectopic pregnancy; ~50% of pregnancies that occur with IUD are likely to be ectopic
Severe infection, including group A streptococcal sepsis reported
Bleeding pattern alterations may occur, including amenorrhea, infrequent bleeding, prolonged bleeding, or irregular bleeding
Increases risk for pelvic inflammatory disease
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
Expulsion may occur resulting in loss of contraceptive protection
Product not intended for use in menopausal women
Women with symptomatic actinomycosis should have device removed and should receive antibiotics
Ovarian cysts may occur
MRI
- Safe scanning with MRI may occur under specific conditions
- static magnetic field ≤3 Tesla
- spatial gradient field ≤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 disease such as stroke or myocardial infarction
- Consider removing device if jaundice or uterine or cervical malignancy occur during use
Pregnancy and lactation
Pregnancy category: X
To decrease the risk of perforation postpartum, 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
Lactation: controversial; not recommended as contraceptive method of choice during lactation by manufacturer (see Cautions and perforation)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Mirena, Skyla (levonorgestrel intrauterine)
Mechanism of action
Synthetic progestin, inhibits ovulation by negative feedback mechanism on hypothalamus, leading to reduced secretion of FSH and LH
Pharmacokinetics
Duration of action: 5 years
Protein Bound: 50%
Vd: Implant (subdermal): 260 L/kg
Metabolism: Liver
Metabolites: tetrahydrolevonorgestrels, hydroxynorgestre, conjugates of sulfate or glucuronide
Half-Life: 11-45 hr
Excretion: Mainly in urine
