ParaGard T 380A

6 ADVERSE 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 name of manufacturer at toll-free phone # or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Table 2: Summary of Rates* (No. per 100 Subjects) by Year for Adverse Reactions Causing Discontinuation 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 [see Clinical Studies ( 14 )]. The WHO Study 79914 was a randomized, multicenter, multinational study of copper T IUSs, including Paragard in 1,396 women outside the US. In the WHO Study, 100% were parous and the mean age at enrollment was 29 years old. The US 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 US. In the US 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 *Rates were calculated by weighting the annual rates by the number of subjects starting each year for each of the US 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. 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 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

4 CONTRAINDICATIONS The use of Paragard is contraindicated when one or more of the following conditions exist: Pregnancy or suspicion of pregnancy [see Warnings and Precautions ( 5.1 , 5.2 ) and Use in Specific Populations ( 8.1 )] Abnormalities of the uterus resulting in distortion of the uterine cavity Acute pelvic inflammatory disease (PID) [see Warnings and Precautions ( 5.4 )] Postpartum endometritis or postabortal endometritis in the past 3 months [see Warnings and Precautions ( 5.4 )] Known or suspected uterine or cervical malignancy 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 ( 5.4 )] Wilson’s disease [see Warnings and Precautions ( 5.9 )] A previously placed IUD or IUS that has not been removed Hypersensitivity to any component of Paragard including to copper or any of the trace elements present in the copper component of Paragard [see Adverse Reactions ( 6.2 ) and Description ( 11 )] Pregnancy or suspicion of pregnancy ( 4 ) Abnormalities of the uterus resulting in distortion of the uterine cavity ( 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 ) 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 IUD or IUS that has not been removed ( 4 ) Hypersensitivity to any component of Paragard including copper or any trace elements present in the copper components of Paragard ( 4 )

11 DESCRIPTION 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 1) [see Dosage and Administration ( 2.3 )]. A monofilament polyethylene thread is tied through the tip, resulting in two white threads, each at least 10.5 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. Paragard and its components are not made with natural rubber latex. Paragard is packaged together with an insertion tube and solid white rod in a Tyvek® polyethylene pouch that is then sterilized. 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 1) [see Dosage and Administration ( 2.3 )].

2 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: 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 [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 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 [see Warnings and Precautions ( 5.4 )]. 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 [see Warnings and Precautions ( 5.4 )]. 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.

1 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 )

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

12 CLINICAL PHARMACOLOGY 12.1 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.

12.1 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.

20190901

5

3 DOSAGE FORMS AND STRENGTHS Paragard is a T-frame copper-containing intrauterine system (IUS) consisting of a polyethylene frame with barium sulfate measuring 32 mm horizontally and 36 mm vertically, with approximately 176 mg of copper wire wrapped around the vertical arm and an approximately 68.7 mg copper wire collar placed on each side of the horizontal arm with a total exposed copper surface area is 380 ± 23 mm², packaged with an insertion tube with blue flange and solid white rod. A monofilament polyethylene thread is tied through the tip of the vertical arm resulting in two white threads, each at least 10.5 cm in length. Figure 1 displays the contents of the package [see Dosage and Administration ( 2.3 )]. One sterile, T-frame IUS containing copper consisting of a T-shaped polyethylene frame with a total exposed copper surface area of 380 ± 23 mm², (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) packaged together with an insertion tube with blue flange and solid white rod. ( 3 , 16 )

ParaGard T 380A Copper COPPER COPPER POLYETHYLENE GLYCOL, UNSPECIFIED BARIUM SULFATE

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Adequate long-term studies in animals to assess the carcinogenic potential of a copper-containing IUS have not been performed. The genotoxic potential of a copper-containing IUS has not been evaluated.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Adequate long-term studies in animals to assess the carcinogenic potential of a copper-containing IUS have not been performed. The genotoxic potential of a copper-containing IUS has not been evaluated.

NDA018680

ParaGard T 380A

Copper

59365-5128

HUMAN PRESCRIPTION DRUG

INTRAUTERINE

PRINCIPAL DISPLAY PANEL PARAGARD Intrauterine Copper Contraceptive 1 Unit ParaGard® T380A Intrauterine Copper Contraceptive Single Carton Text CooperSurgical, Inc. 95 Corporate Drive, Trumbull, CT 06611 USA 1 UNIT PARAGARD ® T380A intrauterine copper contraceptive NDC 59365-5128-1 Each unit wound with approximately 176 mg of copper wire. In addition, a single copper sleeve is swaged on each of the two transverse arms. Each sleeve contains approximately 68.7 mg of copper. The total surface area of copper on the device is 380 ± 23mm 2 . IMPORTANT: To be inserted in the uterus only by a licensed clinician or under the supervision of a physician. See detailed instructionsf or use. NOTE : A Patient Package Insert is provided with each unit. Please ensure that this package insert is provided to the patient. Review patient brochure with each patient before insertion. Store at controlled room temperature: 59° to 86°F (15° to 30°C) CooperSurgical, Inc., 95 Corporate Drive, Trumbull, CT 06611 PARAGARD Intrauterine Copper Contraceptive 1 Unit

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Before inserting Paragard, counsel patients on the following: Sexually Transmitted Infections: Advise patients that Paragard does not protect against HIV infection and other sexually transmitted diseases. Ectopic Pregnancy: Advise patients to report pregnancies and be evaluated immediately, as a pregnancy with Paragard in place is more likely to be an ectopic pregnancy, and the risks of ectopic pregnancy include the loss of fertility [see Warnings and Precautions ( 5.1 )]. Intrauterine Pregnancy: Advise patients to report pregnancies and be evaluated immediately, as an intrauterine pregnancy with Paragard in place, may result in septic abortion, with septicemia, septic shock, and possible death. 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. If Paragard remains in the uterus during a pregnancy, there is an increased risk of miscarriage, sepsis, premature labor and premature delivery. Advise patients that a pregnancy must be followed closely and advise patients to report immediately any symptom, such as flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge or leaking of fluid, or any other symptom that suggests complications of the pregnancy [see Warnings and Precautions ( 5.2 )]. Sepsis: Advise patients that sepsis may occur after insertion of Paragard and to seek immediate treatment for fever and pelvic pain that occurs soon after insertion, as untreated sepsis can result in death [see Warnings and Precautions ( 5.3 )]. Pelvic Inflammatory Disease: Advise patients that pelvic inflammatory disease (PID) may occur after insertion of Paragard and that PID can cause tubal damage leading to ectopic pregnancy or infertility, or can necessitate hysterectomy, or cause death. Advise patients to recognize and report promptly any symptoms of PID including development of menstrual disorders (prolonged or heavy bleeding), unusual vaginal discharge, abdominal or pelvic pain or tenderness, dyspareunia, chills, and fever [see Warnings and Precautions ( 5.4 )]. Embedment, Perforation, and Expulsion : Advise patients regarding the risks of embedment, perforation, and expulsion and inform patients that in some cases, removal of Paragard may be difficult and surgical removal may be necessary. Inform patients that perforation can cause infection, scarring, damage to other organs, pain, or infertility. Inform patients that excessive pain or vaginal bleeding during IUS placement, worsening pain or bleeding after placement, or the inability to feel the IUS strings may occur with IUS perforation and expulsion. There is no protection from pregnancy if Paragard is displaced or expelled. [see Warnings and Precautions ( 5.5 , 5.6 , 5.7 ).] Bleeding Pattern Alterations : Advise patients that heavier or longer periods and spotting between periods may occur. Instruct patients to report continued or severe symptoms to their healthcare provider [see Warnings and Precautions ( 5.9 )]. Checking for Paragard: Advise patients to check that Paragard is still in the uterus by reaching up to the top of the vagina with clean fingers to feel the two threads. Inform patients not to pull on the threads, which could displace Paragard. Advise patients to promptly report if there are changes in the length of the two threads, if they cannot locate the threads, or they can feel any other part of Paragard besides the threads. Magnetic Resonance Imaging (MRI) Safety Information: Inform patients that Paragard can be safely scanned with MRI only under specific conditions. Instruct patients who will have an MRI to tell their healthcare provider that they have Paragard [see Warnings and Precautions ( 5.10 )]. Medical Diathermy: Instruct patients to tell their healthcare provider that they have Paragard prior to undergoing medical diathermy [see Warnings and Precautions ( 5.11 )]. Other Important Information: Advise patients to contact their healthcare provider if any of the following occur: ●Pelvic pain or pain during sex ● Unusual vaginal discharge or genital sores ● Possible exposure to STIs ● HIV positive seroconversion in herself or her partner ● Severe or prolonged vaginal bleeding ● Missed period Advise patients that they may use tampons or pads while wearing Paragard. Manufactured by: CooperSurgical, Inc. Trumbull, CT 06611

14 CLINICAL STUDIES The efficacy of Paragard for use in females of reproductive potential for prevention of pregnancy for up to 10 years was demonstrated in two trials: 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 several randomized, double-blind, comparative studies of copper T IUSs, including Paragard in 3,536 women in the US. In the US study, 64% were nulliparous, 49% were nulligravida; 68% were under age 25 at the time of enrollment (median age 23 years old). The pregnancy rate in the two clinical studies with Paragard was less than 1 pregnancy per 100 women each year (see Table 3). Table 3: Pregnancy Rates* (Number of Pregnancies per 100 Women) by Year in the WHO and U.S. Studies *Rates were calculated by weighting the annual rates by the number of subjects starting each year for each of the US Composite Study (3536 subjects) and the World Health Organization (1396 subjects) trials. Table 3: Pregnancy Rates* (Number of Pregnancies per 100 Women) by Year in the WHO and U.S. Studies

8.5 Geriatric Use Paragard has not been studied in women over 65 years of age and is not indicated in this population.

8.4 Pediatric Use The safety and effectiveness of Paragard have been established in females of reproductive potential. Efficacy is expected to be the same for postmenarcheal females regardless of age. Paragard is not indicated in females before menarche.

8.1 Pregnancy Risk Summary Use of Paragard is contraindicated for use in pregnant females because there is no need for pregnancy prevention in a female who is already pregnant and Paragard may cause adverse pregnancy outcomes. If a female becomes pregnant with Paragard in place, there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 , 5.2 )]. Advise the female of the potential risks if pregnancy occurs with Paragard 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 Paragard and birth defects have not been conducted.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Use of Paragard is contraindicated for use in pregnant females because there is no need for pregnancy prevention in a female who is already pregnant and Paragard may cause adverse pregnancy outcomes. If a female becomes pregnant with Paragard in place, there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 , 5.2 )]. Advise the female of the potential risks if pregnancy occurs with Paragard 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 Paragard and birth defects have not been conducted. 8.2 Lactation Risk Summary No difference has been detected in concentration of copper in human milk before and after insertion of copper IUSs, including Paragard. There is no information on the effect of copper in a breastfed child or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Paragard and any potential adverse effects on the breastfed child from Paragard. 8.4 Pediatric Use The safety and effectiveness of Paragard have been established in females of reproductive potential. Efficacy is expected to be the same for postmenarcheal females regardless of age. Paragard is not indicated in females before menarche. 8.5 Geriatric Use Paragard has not been studied in women over 65 years of age and is not indicated in this population.

16 HOW SUPPLIED/STORAGE AND HANDLING Paragard (intrauterine copper contraceptive) is available in cartons of 1 (one) sterile unit (NDC 59365-5128-1). Each Paragard is white, T-shaped, and measures 32 mm horizontally and 36 mm vertically, with approximately 176 mg of copper wire wrapped around the vertical arm and an approximately 68.7 mg copper wire collar placed on each side of the horizontal arms, and with a monofilament polyethylene thread tied through the tip of the vertical arm [see Dosage and Administration ( 2.3 )]. The T-frame is made of polyethylene with barium sulfate. Each Paragard is packaged together with an insertion tube with blue flange and solid white rod in a Tyvek® polyethylene pouch. Store at controlled room temperature: 59° to 86°F (15° to 30°C).