COPPER: 38,277 Adverse Event Reports & Safety Profile

Figure 10 Figure 11

11.1 Paragard IUS Paragard (intrauterine copper contraceptive) is a T-shaped intrauterine system (IUS), measuring 32 mm horizontally and 36 mm vertically, with a 3 mm diameter bulb at the tip of the vertical stem. (See Figure 10) <span class="opacity-50 text-xs">[see Dosage and Administration (2.3)]</span>. A monofilament polyethylene thread is tied through the tip, resulting in two white threads, each approximately 36.5 cm in length, to aid in detection and removal of the intrauterine system. The T-frame is made of polyethylene with barium sulfate to aid in detecting the intrauterine system under x-ray. Paragard also contains copper (approximately 176 mg of wire wrapped around the vertical stem and an approximately 68.7 mg collar placed on each side of the horizontal arm). The total exposed copper surface area is 380 ± 23 mm².

One

Paragard weighs less than one (1) gram.

Figure

10 – Paragard IUS Paragard, its components, and the packaging are not made with natural rubber latex.

11.2 Inserter Paragard is packaged with a sterile pre-assembled inserter as a single-use, disposable device in a tray and in a Tyvek ® polyethylene pouch. A moveable blue flange on the insertion tube aids in gauging the depth of insertion through the cervical canal and into the uterine cavity (See Figure 11) <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.3 )]</span>.

Figure

11 – Paragard with Inserter

AND USAGE Paragard is indicated for prevention of pregnancy in females of reproductive potential for up to 10 years. Paragard is a copper-containing intrauterine system (IUS) indicated for prevention of pregnancy in females of reproductive potential for up to 10 years. ( 1 )

AND ADMINISTRATION Insert a single Paragard at the fundus of the uterine cavity.

Remove

Paragard no later than 10 years from the date of insertion. ( 2.1 ) Insert and remove Paragard only if you are a healthcare provider trained on these procedures. ( 2.1 ) See the Full Prescribing Information for recommended timing of insertion preparation instructions, insertion procedures, postplacement management, and instructions on removing Paragard ( 2.2 , 2.3 , 2.4 , 2.5 , 2.6 ) Following the insertion, examine the patient after her first menses to confirm Paragard is still in place. ( 2.5 )

Figure

1: Paragard Intrauterine System (IUS) with Insertion Tube and Solid White Rod Figure 2: Inserting Tips of T-Arms of Paraguard into Insertion Tube Figure 3: Bending T-Arms of Paraguard While in Sterile Packaging Figure 4: Inserting Tips of T-Arms of Paraguard into Insertion Tube While in Sterile Packaging Figure 5: Insertion Tube with Paraguard in Uterus Figure 6: Release of T-Arms of Paraguard in Uterus Figure 7: Placement of Paraguard in Fundus of Uterus Figure 8: Withdraw Solid White Rod from Uterus Figure 9: Appropriate Paraguard Placement in Uterus

2.1 Important Dosage and Administration Instructions Paragard should only be inserted by a healthcare provider trained in Paragard’s insertion procedures, because insertion for Paragard is different from that used for other intrauterine systems. Healthcare providers should become thoroughly familiar with the product, product educational materials, product insertion instructions, and prescribing information before attempting insertion of Paragard. Insert one Paragard at the fundus of the uterine cavity <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.4 )]</span>.

Remove

Paragard on or before 10 years from the date of insertion [see Dosage and Administration ( 2.6 )]. May replace Paragard at the time of removal with a new Paragard if continued contraceptive protection is desired. Before considering use of Paragard, make sure that the female is an appropriate candidate for Paragard. Exclude pregnancy (consider the possibility of ovulation and conception) prior to use [see Contraindicati ons ( 4 ) and Warnings and Precautions ( 5.2 )].

2.2 Timing of Insertion Refer to Table 1 for recommended timing of Paragard insertion.

Table

1: Recommended Timing of Paragard Insertion Clinical Situation Recommended Timing of Paragard Insertion 1.

Start

Paragard in females not currently using contraception At any time during the menstrual cycle. 2. Switch to Paragard from an oral, transdermal, or vaginal form of hormonal contraception or an injectable progestin contraceptive At any time during the menstrual cycle; discontinue the previous method. 3. Switch to Paragard from a contraceptive implant or other intrauterine system Same day the implant or IUS is removed (insert at any time during the menstrual cycle). 4.

Insert

Paragard after abortion or miscarriage Immediately after abortion, although immediate placement has a slightly higher risk of expulsion than placement at other times. Insertion after second trimester abortion is associated with a higher risk of expulsion than insertion after a first trimester abortion. 5.

Insert

Paragard after Childbirth May insert immediately postpartum. Insertion before uterine involution is complete, which may not occur until the second postpartum month, has been associated with increased risk of expulsion [see Warnings and Precautions ( 5.6 , 5.7 )]. There appears to be an increased risk of perforation in lactating women [see Warnings and Precautions ( 5.6 )].

2.3 Preparation Instruction Before insertion: Use strict aseptic techniques throughout preparation <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.4 )]</span>. Prepare placement tools (e.g., speculum, cotton swab, tenaculum, uterine sound, scissors, and forceps). Place the package containing Paragard (face-up), sterile card, and solid white rod on a sterile field (see Figure 1) and open package from the bottom end where arrow says “open”.

Figure

1: Paragard Intrauterine System (IUS) with Insertion Tube and Solid White Rod Consider the use of an analgesic Establish the size and position of the uterus by performing a bi-manual examination. Insert a speculum and, using a cotton swab, cleanse the cervix and vagina with an antiseptic solution. Apply a tenaculum to the cervix and use gentle traction to align the cervical canal with the uterine cavity. Gently insert a sterile uterine sound to measure the depth of the uterine cavity. The uterus should sound to a depth of 6 to 9 cm except when inserting Paragard immediately postabortion or immediately postpartum. Insertion of Paragard may be associated with pain and/or bleeding or vasovagal reactions (e.g. syncope, bradycardia, or seizure) especially in patients with a predisposition to these symptoms. Insertion into a uterine cavity measuring less than 6 cm may increase the incidence of expulsion, bleeding, pain, and perforation. If cervical stenosis is encountered, avoid undue force. Dilators and analgesia/local anesthesia may be helpful in this situation.

2.4 Insertion Procedure Use strict aseptic techniques throughout the insertion procedure <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.4 )]</span>. Using sterile gloves, bend the T-Arms of Paragard by folding the two horizontal arms down against the stem. Slightly withdraw insertion tube, push arms down along the stem, slide insertion tube over the tips of the T-Arms (see Figure 2). Only the tips of the T-Arms should be in the insertion tube. Do not advance beyond the copper collars. Insert solid white rod into bottom of insertion tube until it touches the bottom of the IUS. Do not leave the horizontal arms of Paragard bent for more than 5 minutes, as the arms may not open properly.

Figure

2: Inserting Tips of T-Arms of Paraguard into Insertion Tube Although using sterile gloves is recommended, in situations where sterile gloves are not available, you can perform this step while Paragard is in the sterile package. Place the package face up on a clean surface. Open from the bottom end where arrow says “open”. Pull the solid white rod from the package and put it back in the package laying it carefully alongside the insertion tube, making sure the distal end of the rod remains sterile. Place thumb and index finger on the outside of the package, on top of the ends of the horizontal arms. Use other hand to push insertion tube against arms of Paragard (shown by arrow in Figure 3). This will start bending the T-Arms downward. Note that the arms of Paragard should be folded downward to ensure proper insertion.

Figure

3: Bending T-Arms of Paraguard While in Sterile Packaging Bring the thumb and index finger closer together on the outside of the package to continue bending the arms until they are alongside the stem. Use the other hand to withdraw the insertion tube slightly so that the insertion tube can be pushed and rotated over the tips of the T-Arms (see Figure 4). Only the tips of the T-Arms should be in the insertion tube. Do not advance beyond the copper collars. Insert solid white rod into bottom of the insertion tube until it touches the bottom of the IUS. Do not leave the horizontal arms of Paragard bent for more than 5 minutes, as the arms may not open properly.

Figure

4: Inserting Tips of T-Arms of Paraguard into Insertion Tube While in Sterile Packaging Once the above steps are completed and Paragard is in the insertion tube, grasp the insertion tube at the open end of the package; adjust the blue flange so that the distance from the top of the Paragard insertion tube is the same as the uterine depth measured with the uterine sound or use the sterile card to adjust the blue flange according to the premeasured uterine depth. Rotate the blue flange so that the horizontal arms of Paragard and the long axis of the blue flange lie in the same horizontal plane to ensure the arms open up in the proper direction. To orient the uterus in an axial position, apply gentle traction to the tenaculum. Then pass the loaded insertion tube through the cervical canal until Paragard just touches the fundus of the uterus. The blue flange should be at the cervix in the horizontal plane (see Figure 5).

Figure

5: Insertion Tube with Paraguard in Uterus Release the arms of Paragard by holding the solid white rod steady and withdrawing the insertion tube no more than one centimeter. This releases the arms of Paragard high in the uterine fundus (see Figure 6).

Figure

6: Release of T-Arms of Paraguard in Uterus Gently and carefully move the insertion tube upward toward the fundus of the uterus, until slight resistance is felt. This will ensure placement of Paragard at the highest possible position within the uterus (see Figure 7). Do not use the white rod as a plunger to push or insert Paragard.

Figure

7: Placement of Paraguard in Fundus of Uterus Hold the insertion tube steady and withdraw the solid white rod (see Figure 8). Do not remove the solid white rod and the insertion tube at the same time to prevent accidental pulling of the threads.

Figure

8: Withdraw Solid White Rod from Uterus Gently and slowly withdraw the insertion tube from the cervical canal. Only the threads should be visible protruding from the cervix (see Figure 9). Trim the threads so that 3 to 4 cm protrude into the vagina. Measure the length of protrusion of the threads. Recommend recording length of threads, date of placement and Paragard lot number.

Figure

9: Appropriate Paraguard Placement in Uterus If you suspect that Paragard is not in the correct position, check placement (with ultrasound, if necessary).

If

Paragard is not positioned completely within the uterus, remove it and replace it with a new Paragard. Do not reinsert an expelled or partially expelled Paragard.

2.5 Postplacement Management of Paraguard Following placement: Examine the female after her first menses to confirm that Paragard is still in place. You should be able to visualize or feel only the threads. The length of the visible threads may change with time. However, no action is needed unless you suspect partial expulsion, perforation, pregnancy, or breakage. If you cannot find the threads in the vagina, check that Paragard is still in the uterus. The threads can retract into the uterus or break, or Paragard can break, perforate the uterus, or be expelled. Gentle probing of the cavity, x-ray, or sonography may be required to locate Paragard Remove Paragard if it has been partially expelled or perforated the uterus [ see Warnings and Precautions ( 5.6 , 5.7 )]. Do not reinsert a used Paragard.

2.6 Removal of Paraguard Timing of Removal Paragard can be removed at any time prior to 10 years after insertion.

Remove

Paragard no later than 10 years after insertion. A new Paragard can be inserted at the time of removal if continued contraceptive protection is desired.

Removal Instructions

Use a speculum and visualize the cervix.

Remove

Paragard with forceps, pulling gently on the exposed threads. The arms of Paragard will fold upwards as it is withdrawn from the uterus. Breakage or embedment of Paragard in the myometrium can make removal difficult [see Warnings and Precautions, ( 5.5 )]. Analgesia, paracervical anesthesia, cervical dilation, alligator forceps or other grasping instrument, or hysteroscopy may assist in removing an embedded Paragard. Make sure Paragard is intact upon removal. Removal may be associated with some pain and/or bleeding or vasovagal reactions (e.g. syncope, bradycardia, seizures) especially in patients with a predisposition to these conditions.

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 )

REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Ectopic pregnancy [see Warnings and Precautions ( 5.1 )] Intrauterine pregnancy [see Warnings and Precautions ( 5.2 )] Septic abortion [see Warnings and Precautions ( 5.2 )] Group A Streptococcal Sepsis (GAS) [see Warnings and Precautions ( 5.3 )]

Pelvic Inflammatory

Disease and Endometritis [see Warnings and Precautions ( 5.4 )] Embedment [see Warnings and Precautions ( 5.5 )] Perforation [see Warnings and Precautions ( 5.6 )] Expulsion [see Warnings and Precautions ( 5.7 )]

Bleeding Pattern

Alterations [see Warnings and Precautions ( 5.9 ) ] Adverse reactions reported in clinical trials include: anemia, backache, dysmenorrhea, dyspareunia, expulsion (complete or partial), prolonged menstrual flow, menstrual spotting, pain and cramping, and vaginitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact CooperSurgical, Inc. at 1-877-727-2427 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical 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 in two trials <span class="opacity-50 text-xs">[see Clinical Studies ( 14 )]</span>. The WHO Study 79914 was a randomized, multicenter, multinational study of copper T IUSs, including Paragard in 1,396 women outside the U.S. In the WHO Study, 100% were parous and the mean age at enrollment was 29 years old. The U.S.

Composite

Study was a meta-analysis that evaluated randomized, double-blind, comparative studies of copper T IUSs, including Paragard in 3,536 women in the U.S. In the U.S.

Composite

Study, 64% were nulliparous, 49% were nulligravida, 68% were under age 25 at the time of enrollment (median age 23 years old).

Table

2 shows discontinuation rates from the two clinical studies by adverse reaction and year.

Table

2: Summary of Rates* (No. per 100 Subjects) by Year for Adverse Reactions Causing Discontinuation Year 1 2 3 4 5 6 7 8 9 10 Number of Women at Start of Year 4,932 3,149 2,018 1,121 872 621 563 483 423 325 Expulsion 5.7 2.5 1.6 1.2 0.3 0.0 0.6 1.7 0.2

0.4 Bleeding/Pain 11.9 9.8 7.0 3.5 3.7 2.7 3.0 2.5 2.2

3.7 Other Medical Event 2.5 2.1 1.6 1.7 0.1 0.3 1.0 0.4 0.7 0.3 *Rates were calculated by weighting the annual rates by the number of subjects starting each year for each of the U.S.

Composite

Study (3536 subjects) and the World Health Organization (1396 subjects) trials. The following adverse reactions have also been observed: anemia, backache, dysmenorrhea, dyspareunia, complete or partial expulsion, prolonged menstrual flow, menstrual spotting, pain and cramping, and vaginitis. Study CSIPD-001 The Paragard inserter that enables single-hand insertion was evaluated in Study CSIPD-001. A total of 117 females of reproductive potential aged 18 to 49 years, underwent Paragard insertion and were followed for up to 12 weeks of Paragard use. Subjects were predominantly white (76%), 45% were parous, and 35% were obese. Successful placement of Paragard with first attempt occurred in 91% of the subjects and 99% with two insertion attempts. Adverse reactions of special interest occurring during the study were IUS expulsion (2.6%), vasovagal reaction (2.6%), IUS malposition (1.7%), partial uterine perforation (0.9%), and IUS embedment (0.9%).

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Paragard. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal

Disorders: abdominal distension, nausea General Disorders and Administration Site Conditions: device breakage, pyrexia; copper wire breakage Immune System Disorders: allergy to metals, hypersensitivity Infections and Infestations: endometritis/uterine infection Musculoskeletal and Connective Tissue Disorders: muscle spasms Nervous System Disorders: dizziness Reproductive System and Breast Disorders: amenorrhea Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome

AND PRECAUTIONS 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 )

5.1 Risk 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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span>.

5.2 Miudella 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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span>. 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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span>. 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.

5.3 Risk 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).

5.4 Risks 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.

5.5 Sepsis 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.

5.6 Pelvic 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.

5.7 Perforation 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 inserted when the uterus is fixed, retroverted or not completely involuted during the postpartum period. If perforation is suspected or if known perforation occurs during placement, the IUS should be removed as soon as possible. Surgery may be required. Preoperative imaging followed by laparoscopy or laparotomy may be required to remove the IUS from the peritoneal cavity. Delayed detection or removal of Miudella in cases of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal penetration, intestinal obstruction, abscesses and/or damage to adjacent organs.

5.8 Expulsion Partial or complete expulsion of Miudella has been reported, resulting in the loss of contraceptive protection. The incidence of expulsion in the clinical trials with Miudella was 3.6% through 3 years of use. Consider further diagnostic imaging, such as x-ray, to confirm expulsion if the IUS is not found in the uterus on ultrasound. Miudella should be placed no earlier than 4 weeks post-pregnancy to mitigate the risk of expulsion that may be increased when the uterus is not completely involuted at the time of insertion. Remove a partially expelled Miudella and do not attempt to push a partially expelled Miudella into the uterus. If expulsion has occurred, a new Miudella may be inserted when there is reasonable certainty the patient is not pregnant.

5.9 Wilson&apos;s Disease Miudella may exacerbate Wilson&apos;s disease, a rare genetic disease affecting copper excretion; therefore, the use of Miudella is contraindicated in females with Wilson&apos;s disease <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .

5.10 Bleeding Pattern Alterations Miudella can alter the bleeding pattern and result in heavier and longer menstrual cycles with intermenstrual spotting. In three clinical trials with Miudella <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> , menstrual changes were the most common medical reason for discontinuation. Discontinuation rates for pain and bleeding combined were highest in the first year of use and diminished thereafter. The percentage of females who discontinued Miudella because of bleeding problems or pain during this study ranged from 8.5% in the first year to 3.2% in Year 3. Females complaining of heavy vaginal bleeding should be evaluated and treated, and may need to discontinue Miudella <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> .

5.11 Magnetic Resonance Imaging (MRI)

Safety

Information MRI Safety Information MR Conditional The Miudella Intrauterine Device (IUD) is MR Conditional. A patient with Miudella may be safely scanned under the following conditions. Failure to follow these conditions may result in injury to the patient.

Nominal

Values of Static Magnetic Field (T) 1.5-Tesla or 3.0-Tesla Maximum Spatial Field Gradient 40 T/m (4,000 gauss/cm) Type of RF Excitation Circularly Polarized (CP) (i.e., Quadrature-Transmission) Transmit RF Coil Information There are no transmit RF coil restrictions. Accordingly, the following may be used: body transmit RF coil and all other RF coil combinations (i.e., body RF coil combined with any receive-only RF coil, transmit/receive head RF coil, transmit/receive knee RF coil, etc.)

Operating Mode Normal Operating Mode

Maximum Whole-Body Averaged SAR 2 W/kg (Normal Operating Mode) Limits on Scan Duration 2 W/kg whole body average SAR for 60 minutes of continuous RF exposure (a sequence or back to back sequences/series without breaks) MR Image Artifact The presence of this implant produces an imaging artifact. In testing with gradient-echo sequencing, the shape of the image artifact follows the approximate contour of the device and extends radially up to 0.7 cm from the device. Image

5.12 Medical Diathermy Medical equipment that contains high levels of Radiofrequency (RF) energy such as diathermy may cause health effects (by heating tissue) in females with a metal-containing IUS including Miudella. Avoid using high medical RF transmitter devices in females with Miudella.

INTERACTIONS No drug-drug interaction or drug-herbal supplement interaction studies have been conducted with Paragard.

Drug Facts Active Ingredients: (HPUS*) 20% of each Cerebrum 21X Cuprum met 21X Ferrum met 6X Formicum acidum 21X Silicea 12X *The letters "HPUS" indicate that the components in this product are officially monographed in the Homeopathic Pharmacopoeia of the United States. †Claims based on traditional homeopathic practice, not accepted medical evidence. Not FDA evaluated.

Inactive Ingredients: Spring water, Stearic acid, Isopropyl myristate, Lavender oil, Cetyl alcohol, Polyoxyl 40 stearate, Stearyl alcohol, Xanthan gum, Glycerin, Sorbic acid, Tea tree oil, Frankincense oil, Myrrh oil, Grapefruit seed extract Prepared using rhythmical processes.