warnings and cautions
5 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 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.