Miudella is indicated for prevention of pregnancy in females of reproductive potential for up to 3 years. Miudella is a copper-containing intrauterine system (IUS) indicated for prevention of pregnancy in females of reproductive potential for up to 3 years.( 1 )
Contraindications
The use of Miudella is contraindicated when one or more of the following conditions exist: Pregnancy or suspicion of pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ] Congenital or acquired abnormalities of the uterus, including leiomyomas, resulting in distortion of the uterine cavity Acute pelvic inflammatory disease (PID) [see Warnings and Precautions (5.6) ] Postpartum endometritis or postabortal endometritis in the past 3 months. [see Warnings and Precautions (5.6) ] Known or suspected uterine or cervical malignancy For use as post-coital contraception (emergency contraception) Uterine bleeding of unknown etiology Untreated acute cervicitis or vaginitis or other lower genital tract infection Conditions associated with increased susceptibility to pelvic infections [see Warnings and Precautions (5.6) ] Wilson's disease [see Warnings and Precautions (5.9) ] A previously placed IUS that has not been removed Hypersensitivity to any component of Miudella including to polypropylene, copper, nitinol, an alloy of nickel and titanium, or any of the trace elements present in the copper component of Miudella [see Adverse Reactions (6) and Description (11) ] .
Persons with allergic reactions to these components may suffer an allergic reaction to this intrauterine system. Prior to placement, patients should be counseled on the materials contained in the IUS, as well as potential for allergy/hypersensitivity to these materials. Pregnancy or suspicion of pregnancy. ( 4 ) Uterine anomaly that distorts the uterine cavity and would be incompatible with correct IUS placement. ( 4 ) Acute pelvic inflammatory disease (PID) ( 4 ) Postpartum endometritis or postabortal endometritis in past 3 months.
( 4 ) Known or suspected uterine or cervical malignancy ( 4 ) For use as post-coital contraception (emergency contraception) ( 4 ) Uterine bleeding of unknown etiology ( 4 ) Untreated acute cervicitis or vaginitis or other lower genital tract infection ( 4 ) Conditions associated with increased susceptibility to pelvic infections ( 4 ) Wilson's disease ( 4 ) A previously placed IUS that has not been removed ( 4 ) Hypersensitivity to any component of Miudella including copper, nitinol or any trace elements present in the copper components of Miudella ( 4 )
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Risk of Ectopic Pregnancy : Promptly evaluate females who become pregnant for ectopic pregnancy while using Miudella. ( 5.3 ) Risks with Intrauterine Pregnancy : Increased risk of spontaneous abortion, septic abortion, premature delivery, sepsis, septic shock, and death if pregnancy occurs. Remove Miudella if pregnancy occurs with Miudella in place. ( 5.4 ) Sepsis : Group A streptococcal infection has been reported; strict aseptic technique is essential during insertion.
( 5.5 ) Pelvic Inflammatory Disease (PID) : Promptly evaluate patients with complaints of fever or abdominal pain after insertion of Miudella. ( 5.6 ) Perforation resulting in embedment or translocation : May reduce contraceptive effectiveness and require surgery. Risk is increased if inserted in postpartum and lactating females and may be increased if inserted in females with fixed, retroverted uteri or noninvoluted uteri.
( 5.7 ) Expulsion : Partial or complete expulsion may occur. Remove a partially expelled Miudella. ( 5.8 ) Bleeding patterns : May be altered and result in heavier and longer bleeding with spotting. ( 5.10 ) MRI Safety Information : Patients using Miudella can be safely scanned with MRI only under certain conditions. ( 5.11 )
5.1Risk of Complications Due to Improper Insertion
Improper insertion of intrauterine systems, including Miudella, increases the risk of perforation, infection, undiagnosed abnormal bleeding, pregnancy loss (if pregnancy occurs with IUS in situ), and expulsion. Proper training prior to first use of Miudella can minimize the risk of improper insertion. Miudella is available only through a restricted program under a REMS [see Warnings and Precautions (5.2) ].
5.2Miudella REMS
Miudella is only available through a restricted program under a REMS called Miudella REMS Program to ensure healthcare providers are trained prior to first use [see Warnings and Precautions (5.1) ]. Notable requirements include the following: Healthcare providers must be certified with the program by enrolling and completing training on the proper insertion of Miudella prior to first use [see Warnings and Precautions (5.2) ].
Pharmacies and healthcare settings that dispense Miudella must be certified by enrolling in the REMS and must only dispense Miudella to certified healthcare providers. Further information is available at miudellarems.com and 1-855-337-0772.
5.3Risk of Ectopic Pregnancy Evaluate
for possible ectopic pregnancy in any female who becomes pregnant while using Miudella because a pregnancy that occurs with Miudella in place is more likely to be ectopic than a pregnancy in the general population. However, because Miudella prevents most pregnancies, females who use Miudella have a lower risk of an ectopic pregnancy than sexually active females who do not use any contraception. The incidence of ectopic pregnancy in the clinical trials with Miudella was approximately 0.3%.
Ectopic pregnancy may require surgery and may result in loss of fertility. Patients who use Miudella should be informed about recognizing the signs and symptoms of ectopic pregnancy and promptly reporting them to their healthcare professional, and about the associated risks of ectopic pregnancy (e.g., loss of fertility).
5.4Risks with Intrauterine Pregnancy
If intrauterine pregnancy occurs with Miudella in place and the thread ends are visible or can be retrieved from the cervical canal, remove Miudella. Leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal of Miudella may also result in spontaneous abortion. In the event of an intrauterine pregnancy with Miudella, consider the following: Septic Abortion In females becoming pregnant with an intrauterine system (IUS), including Miudella in place, septic abortion, with septicemia, septic shock, and death, may occur.
Septic abortion typically requires hospitalization and treatment with intravenous antibiotics. Septic abortion may result in spontaneous abortion or a medical indication for pregnancy termination. A hysterectomy may be required if severe infection of the uterus occurs, which will result in permanent infertility. Continuation of Pregnancy If a female becomes pregnant with Miudella in place and if Miudella cannot be removed or the female chooses not to have it removed, warn her that failure to remove Miudella increases the risk of miscarriage, sepsis, premature labor, and premature delivery.
Prenatal care should include counseling about these risks and that she should report immediately any flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge or leakage of fluid, or any other symptom that suggests complications of the pregnancy.
5.5Sepsis
Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of IUSs. 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 Miudella is essential to minimize serious infections such as GAS.
5.6Pelvic Infection
Promptly examine users with complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding, fever, genital lesions or sores. Remove Miudella in cases of recurrent pelvic inflammatory disease or endometritis, or if an acute pelvic infection is severe or does not respond to treatment. Pelvic Inflammatory Disease (PID) Miudella is contraindicated in the presence of known or suspected PID or endometritis [see Contraindications (4) ] .
IUSs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. Females at increased risk for PID PID is often associated with a sexually transmitted infection (STI), and Miudella does not protect against STI. The risk of PID is greater for females who have multiple sexual partners, and also for females whose sexual partner(s) have multiple sexual partners.
Females who have had PID are at increased risk for a recurrence or re-infection. In particular, ascertain whether the female is at increased risk of infection (for example, leukemia, acquired immune deficiency syndrome [AIDS], intravenous drug abuse). Subclinical PID PID may be asymptomatic but still result in tubal damage and its sequelae. Treatment of PID Following a diagnosis of PID, or suspected PID, bacteriologic specimens should be obtained and antibiotic therapy should be initiated promptly.
Removal of Miudella after initiation of antibiotic therapy is appropriate in cases of recurrent PID or endometritis, or if an acute pelvic infection is severe or does not respond to treatment. Actinomycosis Actinomycosis has been associated with IUS use. Symptomatic patients with known actinomycosis infection should have Miudella removed and receive antibiotics. Actinomycetes can be found in the genital tract cultures in healthy patients without IUSs.
The significance of actinomyces-like organisms on Pap test in an asymptomatic IUS user is unknown, and so this finding alone does not always require Miudella removal and treatment. When possible, confirm a Pap test diagnosis with cultures.
5.7Perforation Partial
or total perforation of the uterine wall or cervix may occur during insertions, although the perforation may not be detected until sometime later. Perforation may also occur at any time during IUS use. Perforation that results in embedment or translocation may reduce contraceptive efficacy and result in pregnancy. The incidence of perforation during or following Miudella insertion in clinical trials was 0.1% (2 out of 1904).
A post-marketing safety study conducted in Europe (EURAS IUS) with IUSs, including copper IUSs, demonstrated an increased risk of perforation in postpartum and lactating women. The risk of perforation may be increased if an IUS, such as Miudella, is
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Pregnancy and breastfeeding
8.1 Pregnancy Risk Summary Use of Miudella is contraindicated for use in pregnant females because there is no need for pregnancy prevention in a female who is already pregnant and Miudella may cause adverse pregnancy outcomes. If a female becomes pregnant with Miudella in place, there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery [see Contraindications (4) and Warnings and Precautions (5.3 , 5.4) ] .
Advise the female of the potential risks if pregnancy occurs with Miudella in place. Published studies on pregnancy outcomes exposed to copper IUSs report up to 27% miscarriage when the IUS was removed compared to 77% miscarriage when the IUS remained in the uterus. Studies on Miudella and birth defects have not been conducted.
Adverse reactions
The following serious adverse reactions are discussed elsewhere in the labeling: Ectopic pregnancy [see Warnings and Precautions (5.3) ] Intrauterine pregnancy [see Warnings and Precautions (5.4) ] Sepsis [see Warnings and Precautions (5.5) ] Pelvic Infection [see Warnings and Precautions (5.6) ] Perforation [see Warnings and Precautions (5.7) ] Expulsion [see Warnings and Precautions (5.8) ] Wilson's Diseas e [see Warnings and Precautions (5.9) ] Bleeding Pattern Alteration [see Warnings and Precautions (5.10) ] Most common adverse reactions (incidence ≥ 5%) are: heavy menstrual bleeding, dysmenorrhea, intermenstrual bleeding, pelvic discomfort, procedural pain, pelvic pain, post procedural hemorrhage, dyspareunia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sebela Women's Health Inc. at 1-866-246-2133 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data described below reflect exposure of 1,904 healthy 17- to 45-year-old women (mean age 27.5 ± 5.72 years) to Miudella. These data come from two multi-center contraceptive trials with a 3-year duration and a single, multi-center comparative bioavailability study with a 3 year duration, all conducted in the United States, enrolling generally healthy, postmenarcheal females to 45 years old.
In total 1,904 subjects were exposed to Miudella for one year and 916 completed three years. The data in these trials cover approximately 51,692 cycles of exposure. The following adverse reactions have been observed in ≥5% of users in clinical trials with Miudella: heavy menstrual bleeding, dysmenorrhea, intermenstrual bleeding, pelvic discomfort, procedural pain, pelvic pain, post procedural hemorrhage, and dyspareunia.
Table 2 shows discontinuation rates from the 3 multi-center clinical studies by adverse reaction and year. Table 2: Summary of Rates Rates were calculated by weighting the annual rates by the number of subjects starting each year. (No. per 100 Subjects) by Year for Adverse Reactions Causing Discontinuation Year 1 2 3 Number of Women at Start of Year 1,904 1,463 1,118 Bleeding/Pain Bleeding/Pain includes the preferred terms (PTs) Abdominal pain, Abdominal pain lower, Post procedural discomfort, Procedural pain, Coital bleeding, Dysmenorrhea, Dyspareunia, Heavy menstrual bleeding, Intermenstrual bleeding, Menometrorrhagia, Pelvic discomfort, Pelvic pain, Polymenorrhea, Uterine hemorrhage, Uterine spasm 8.5 5.1
3.2 Expulsion 1.9 1.0
0.9Other Medical Event Includes
PTs embedded device (n=6) and uterine perforation (n=1) 0.2 0.1
0.3 According to the safety analyses of these three studies, it was determined the incidence of expulsion of Miudella did not vary significantly by body mass index (BMI). There was no statistically significant difference in the incidence of expulsion of Miudella in normal weight versus obese females.
Composition
Active ingredients
COPPER N/A
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application NDA218201.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
