copper 1.75 SQCM Drug Implant

INDICATIONS 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 )

DOSAGE 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 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 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 [see Dosage and Administration ( 2.4 )]. 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 Contraindications ( 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 )]. Note: The inserter provided with Paragard (see Figure 1) and the Insertion Procedure described in subsection 2.4 are not applicable for immediate insertion after childbirth. For immediate insertion post childbirth, remove the inserter and Paragard from the tray, move the button forward and then completely back to release the Paragard unit from the inserter and insert Paragard. 2.3 Preparation Instructions Read the Preparation Instructions and Insertion Procedure before initiating Paragard insertion . Before insertion: Do NOT remove the inserter from the tray before the arms are loaded into the insertion tube. The tray will be used to fold the Paragard arms down and load the IUS into the inserter. Use strict aseptic techniques throughout preparation [see Warnings and Precautions ( 5.4 )]. Prepare placement tools (e.g., speculum, cotton swab, tenaculum, uterine sound, scissors, and forceps). Consider 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, vasovagal reactions (e.g. syncope, bradycardia), or seizure, especially in patients with a predisposition to these conditions. 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 Follow the i nsertion i nstructions exactly as described to ensure proper placement and avoid early release of Paragard from the inserter . Use strict aseptic techniques throughout the insertion procedure [see Warnings and Precautions ( 5.4 )]. Step 1: Opening the Sterile Paragard Package Place the package containing Paragard (face-up) on a flat sterile field (see Figure 1). Open the pouch from the handle end where the arrow on the Placement Guide says “OPEN”. Figure 1: Inserter Figure 2 : Paragard Intrauterine System (IUS) Remove the clear cover from the tray (not shown). Confirm that the top of the button is located at the starting line on the handle prior to loading Paragard. The inserter should remain in the tray until Paragard T-Arms are loaded. Do not slide the button on the handle before folding the arms in the tray. Do not repeatedly slide the button forward and back as this may cause slack in the threads and may result in a n uns uccessful placement . Step 2: Loading Paragard into the Inserter Using sterile gloves, place one hand on the distal end of the tray and the other on the inserter handle. Slide the handle completely forward so that the Paragard advances into the Loading Tip folding the T-Arms of Paragard against the stem (see Figure 3). Figure 3 : Folding Tips of T-Arms of Paragard using Loading Tip Once the T-Arms are folded against the stem, slide the button on the handle completely forward to advance the insertion tube 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. IMPORTANT: Do not leave the T-Arms of Paragard bent for more than 5 minutes, as the arms may not open properly . Figure 4 : Inserting Tips of T-Arms into Insertion Tube Step 3: Adjusting the Flange Once the above steps are completed and Paragard is in the insertion tube, adjust the blue flange. The tray is marked with centimeters and can be used to set the flange to the correct depth (see Figure 5). Adjust the flange so the distance from the top of Paragard (where it protrudes from the inserter) to the top of the flange is equal to the pre-measured uterine depth. Figure 5 : Adjusting the Blue Flange to sound depth Step 4: Removing Inserter from Tray Ensure the button remains in the forward position. To remove the inserter from the tray, gently lift the handle out of the tray, then gently slide the inserter back and lift out of the tray. (see Figure 6). Upon removal from the tray, verify and rotate the blue flange as needed so that the horizontal arms of Paragard and the long axis of the blue flange and handle lie in the same horizontal plane to ensure the arms open in the proper direction. Confirm that both T-Arms are captured within the insertion tube. Figure 6 : Removal of Inserter from Tray Step 5: Inserting Paragard to the Fundus To orient the uterus in an axial position, apply gentle traction to the tenaculum. While holding the button forward, pass the loaded in

WARNINGS AND PRECAUTIONS Ectopic Pregnancy : Promptly evaluate women who become pregnant for ectopic pregnancy while using Paragard. ( 5.1 ) Risks with Intrauterine Pregnancy : Increased risk of spontaneous abortion, septic abortion, premature delivery, sepsis, septic shock and death if pregnancy occurs. Remove Paragard if pregnancy occurs with Paragard in place. ( 5.2 ) Sepsis : Group A streptococcal infection has been reported; strict aseptic technique is essential during insertion ( 5.3 ) Pelvic Inflammatory Disease (PID) and Endometritis : Before using Paragard, consider the risks of PID and endometritis. Promptly assess and treat patients with signs and symptoms of PID. ( 5.4 ) Embedment : Surgical removal may be necessary. ( 5.5 ) Perforation : May reduce contraceptive effectiveness and require surgery. Risk is increased if inserted in lactating women and may be increased if inserted in women with fixed, retroverted uteri or noninvoluted uteri. ( 5.6 ) Expulsion : Partial or complete expulsion may occur. Remove a partially expelled Paragard. ( 5.7 ) Bleeding patterns : May be altered and result in heavier and longer bleeding with spotting. ( 5.9 ) MRI Safety Information : Patients using Paragard can be safely scanned with MRI only under certain conditions. ( 5.10 ) MR 5.1 Ectopic Pregnancy Evaluate for possible ectopic pregnancy in any female who becomes pregnant while using Paragard because a pregnancy that occurs with Paragard in place is more likely to be ectopic than a pregnancy in the general population. However, because Paragard prevents most pregnancies, females who use Paragard 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 Paragard (which excluded females with a previous history of ectopic pregnancy) was approximately 0.06%. Ectopic pregnancy may require surgery and may result in loss of fertility. 5.2 Risks with Intrauterine Pregnancy If intrauterine pregnancy occurs with Paragard in place and the strings are visible or can be retrieved from the cervical canal, remove Paragard because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal of Paragard may also result in spontaneous abortion. In the event of an intrauterine pregnancy with Paragard, consider the following: Septic Abortion In females becoming pregnant with an intrauterine system (IUS), including Paragard in place, septic abortion, with septicemia, septic shock, and death, may occur [see Warnings and Precautions ( 5.3 )]. 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 Paragard in place and if Paragard cannot be removed or the female chooses not to have it removed, warn her that failure to remove Paragard 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. 5.3 Sepsis Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of IUSs, including Paragard. 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 Paragard is essential in order to minimize serious infections such as GAS [see Dosage and Administration ( 2.3 )]. 5.4 Pelvic Inflammatory Disease and Endometritis Insertion of Paragard is contraindicated in the presence of known or suspected Pelvic Inflammatory Disease (PID) or endometritis [see Contraindications ( 4 )] . IUSs, including Paragard, have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. In the clinical trials with Paragard, the incidence of PID that resulted in the removal of Paragard was approximately 0.1% [see Clinical Studies ( 14 )]. Counsel women who receive Paragard to notify a healthcare provider if they have complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding, fever, or genital lesions or sores. In such circumstances, perform a pelvic examination promptly to evaluate for possible pelvic infection. Remove Paragard in cases of recurrent PID or endometritis, or if an acute pelvic infection is severe or does not respond to treatment. PID can have serious consequences, such as tubal damage (leading to ectopic pregnancy or infertility), hysterectomy, sepsis, and death. Females at Increased Risk for PID PID or endometritis are often associated with a sexually transmitted infection (STI) and Paragard does not protect against STIs. The risk of PID or endometritis 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 or endometritis are at increased risk for a recurrence or re-infection. In particular, ascertain whether a female is at increased risk of infection (for example, leukemia, acquired immune deficiency syndrome (AIDS), intravenous drug abuse). Asymptomatic PID PID or endometritis may be asymptomatic but still result in tubal damage and its sequelae. Treatment of PID or Endometritis in Patients Using Paragard Remove Paragard in cases of recurrent endometritis or PID, or if an acute pelvic infection is severe or does not respond to treatment. Prophylactic antibiotics administered at the time of insertion do not appear to lower the incidence of PID. Promptly assess and treat any female who develops signs or symptoms of PID. Perform appropriate testing for sexually transmitted infection and initiate antibiotic therapy promptly. Paragard does not need to be removed immediately. Reassess the patient in 48-72 hours. If no clinical improvement occurs, continue antibiotics and consider removal of Paragard. If the decision is to remove Paragard, start antibiotics prior to removal to avoid the potential risk for bacterial spread resulting from the removal procedure. Actinomycosis Actinomycosis has been associated with IUS use, including Paragard. Symptomatic women with known actinomycosis infection should have Paragard removed and receive antibiotics. Actinomycetes can be found in the genital tract cultures in healthy women without IUSs. The significance of actinomyces-like organisms on a Papanicolaou (PAP) smear in an asymptomatic IUS user is unknown, and this finding alone does not always require IUS removal and treatment. When possible, confirm a PAP smear diagnosis with cultures. 5.5 Embedment Partial penetration or embedment of Paragard in the myometrium can make removal difficult. In some cases, surgical removal may be necessary. Breakage of an embedded Paragard during non-surgical removal has been reported [see Dosage and Administration ( 2.6 )]. 5.6 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 reduce contraceptive efficacy and result in pregnancy. The incidence of perforation during or following Paragard insertion in clinical trials was 0.2% (13 out of 5344). Delayed detection or removal of Paragard in cases of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal penetration, intestinal obstruction, abscesses and/or damage to adjac

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 )

Mechanism of Action Copper continuously released into the uterine cavity contributes to the contraceptive effectiveness of Paragard. Mechanism(s) by which copper enhances contraceptive efficacy include interference with sperm transport and fertilization of an egg, and possibly prevention of implantation.