Paragard: Package Insert / Prescribing Info

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.

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 insertion instructions 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 an unsuccessful 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 inserter through the cervical canal until the Paragard reaches the fundus of the uterus. This will ensure placement of Paragard at the highest possible position within the uterus.

• The blue flange should be at the cervix in the horizontal plane. The button should remain in the forward position (see Figure 7).

  Figure 7: Inserter with Paragard at Uterine Fundus

  

Step 6: Releasing Paragard and Withdrawing Inserter

• Release the arms of Paragard by holding the handle steady and sliding the button all the way down (and you may feel a click). Do not stop at the starting line as it is not used for deployment.

• This releases the threads and the T-Arms of Paragard high in the uterine fundus (see Figure 8).

  Figure 8: Release T-Arms of Paragard at Uterine Fundus

  

• Gently and slowly withdraw the inserter from the uterus and cervical canal.
• Only the threads should be visibly protruding from the cervix (see Figure 9). Trim the threads so that 3 to 4 cm protrude into the vagina.
• Measure and note the length of threads, date of placement and Paragard lot number.
• Discard the used inserter – do not attempt to re-use the inserter because it is a single use device.

• 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.

  Figure 9: Appropriate Paragard Placement in Uterus

  

2.5 Postplacement Management of Paragard

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 Paragard

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.
• If removal cannot be accomplished by gentle pulling, consider checking Paragard location and assess for embedment and perforation (with imaging, if necessary).
• Breakage or embedment of Paragard in the myometrium can make removal difficult [see Warnings and Precautions, (5.5)]. IUS breakage may be associated with removal. 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, vasovagal reactions (e.g. syncope, bradycardia), or seizure, especially in patients with a predisposition to these conditions.

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:

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.

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 adjacent organs.

A postmarketing safety study conducted in Europe (EURAS IUD) with IUSs, including copper IUSs, demonstrated an increased risk of perforation in lactating women. The risk of perforation may be increased if an IUS, such as Paragard, is inserted when the uterus is fixed, retroverted or not completely involuted during the postpartum period.

If perforation does occur, locate and remove Paragard promptly. Surgery may be required. Preoperative imaging followed by laparoscopy or laparotomy is often required to remove Paragard from the peritoneal cavity.

5.7 Expulsion

Partial or complete expulsion of Paragard has been reported, resulting in the loss of contraceptive protection. The incidence of expulsion in the clinical trials with Paragard was approximately 2.3%. Consider further diagnostic imaging, such as x-ray, to confirm expulsion if the IUS is not found in the uterus.

Paragard has been placed immediately after delivery, although the risk of expulsion may be increased when the uterus is not completely involuted at the time of insertion. Remove a partially expelled Paragard.

5.8 Wilson's Disease

Paragard may exacerbate Wilson's disease, a rare genetic disease affecting copper excretion; therefore, the use of Paragard is contraindicated in females of reproductive potential with Wilson's disease [see Contraindications (4)].

5.9 Bleeding Pattern Alterations

Paragard can alter the bleeding pattern and result in heavier and longer menstrual cycles with intermenstrual spotting.

In two clinical trials with Paragard, there were reports of oligomenorrhea and amenorrhea; however, a causal relationship between Paragard and these events could not be established. Menstrual changes were the most common medical reason for discontinuation of Paragard. Discontinuation rates for pain and bleeding combined were highest in the first year of use and diminished thereafter. The percentage of females who discontinued Paragard because of bleeding problems or pain during these studies ranged from 12% in the first year to 2% in Year 9. Females complaining of heavy vaginal bleeding should be evaluated and treated, and may need to discontinue Paragard [see Adverse Reactions (6.1)].

5.10 Magnetic Resonance Imaging (MRI) Safety Information

Non-clinical testing has demonstrated that Paragard is MR Conditional. A patient with Paragard can be safely scanned in an MR system meeting the following conditions:

• Static magnetic field of 3.0 T or 1.5T
• Maximum spatial field gradient of 4,000 gauss/cm (40 T/m)
• Maximum MR system reported, whole body averaged specific absorption rate (SAR) of 2 W/kg (Normal Operating Mode)

Under the scan conditions defined above, Paragard is expected to produce a maximum temperature rise of less than 0.5º C after 15 minutes of continuous scanning.

In non-clinical testing, the image artifact caused by the system extended less than 5 mm from the implant when imaged with a gradient echo pulse sequence and a 3.0 T MRI system.

5.11 Medical Diathermy

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

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 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.

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; 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

8.1 Pregnancy

8.2 Lactation

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.

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) [see Dosage and Administration (2.3)]. 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) [see Dosage and Administration (2.3)].

Figure 11 – Paragard with Inserter

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.

13.1 Carcinogenicity, Mutagenicity, 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.

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:

1. 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
2. Advise patients that they may use tampons or pads while wearing Paragard.

Manufactured by:

CooperSurgical, Inc.
Trumbull, CT 06611