FDA label ed8c0b7a-2dac-2bb1-e053-2a95a90aa156

BOXED WARNING WARNING: SERIOUS AND SOMETIMES FATAL INFECTIONS OR BLEEDING See full prescribing information for complete boxed warning. Serious and sometimes fatal infections and bleeding occur very rarely following spontaneous, surgical, and medical abortions, including following Mifepristone tablets, 200mg use. Atypical Presentation of Infection. Patients with serious bacterial infections and sepsis can present without fever, bacteremia or significant findings on pelvic examination. A high index of suspicion is needed to rule out serious infection and sepsis. Bleeding. Prolonged heavy bleeding may be a sign of incomplete abortion or other complications and prompt medical or surgical intervention may be needed. Mifepristone tablets, 200mg is only available through a restricted program called the Mifepristone REMS Program. Before prescribing Mifepristone tablets, 200mg, inform the patient about these risks. Ensure the patient knows whom to call and what to do if she experiences sustained fever, severe abdominal pain, prolonged heavy bleeding, or syncope, or if she experiences abdominal pain or discomfort or general malaise for more than 24 hours after taking misoprostol. Advise the patient to take the MEDICATION GUIDE with her if she visits an emergency room or another healthcare provider who did not prescribe Mifepristone tablets, 200mg, so that provider knows that she is undergoing a medical abortion.

5 WARNINGS AND PRECAUTIONS 5.1 Infection and Sepsis As with other types of abortion, cases of serious bacterial infection, including very rare cases of fatal septic shock, have been reported following the use of Mifepristone tablets, 200mg [see Boxed Warning]. Healthcare providers evaluating a patient who is undergoing a medical abortion should be alert to the possibility of this rare event. A sustained (>4 hours) fever of 100.4°F or higher, severe abdominal pain, or pelvic tenderness in the days after a medical abortion may be an indication of infection. A high index of suspicion is needed to rule out sepsis (e.g., from Clostridium sordellii) if a patient reports abdominal pain or discomfort or general malaise (including weakness, nausea, vomiting or diarrhea) more than 24 hours after taking misoprostol. Very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, tachycardia, hemoconcentration, and general malaise. No causal relationship between Mifepristone tablets, 200mg and misoprostol use and an increased risk of infection or death has been established. Clostridium sordellii infections have also been reported very rarely following childbirth (vaginal delivery and caesarian section), and in other gynecologic and non-gynecologic conditions. 5.2 Uterine Bleeding Uterine bleeding occurs in almost all patients during a medical abortion. Prolonged heavy bleeding (soaking through two thick full-size sanitary pads per hour for two consecutive hours) may be a sign of incomplete abortion or other complications and prompt medical or surgical intervention may be needed to prevent the development of hypovolemic shock. Counsel patients to seek immediate medical attention if they experience prolonged heavy vaginal bleeding following a medical abortion [see Boxed Warning]. Women should expect to experience vaginal bleeding or spotting for an average of 9 to 16 days. Women report experiencing heavy bleeding for a median duration of 2 days. Up to 8% of all subjects may experience some type of bleeding for 30 days or more. In general, the duration of bleeding and spotting increased as the duration of the pregnancy increased. Decreases in hemoglobin concentration, hematocrit, and red blood cell count may occur in women who bleed heavily. Excessive uterine bleeding usually requires treatment by uterotonics, vasoconstrictor drugs, surgical uterine evacuation, administration of saline infusions, and/or blood transfusions. Based on data from several large clinical trials, vasoconstrictor drugs were used in 4.3% of all subjects, there was a decrease in hemoglobin of more than 2g/dL in 5.5% of subjects, and blood transfusions were administered to ≤0.1% of subjects. Because heavy bleeding requiring surgical uterine evacuation occurs in about 1% of patients, special care should be given to patients with hemostatic disorders, hypocoagulability, or severe anemia. 5.3 Mifepristone REMS Program Mifepristone tablets, 200mg is available only through a restricted program called the Mifepristone REMS Program, because of the risks of serious complications [see Warnings and Precautions (5.1, 5.2)] Notable requirements of the Mifepristone REMS Program include the following: Prescribers must be certified with the program by completing the Prescriber Agreement Form Patients must sign a Patient Agreement Form Mifepristone tablets, 200mg must be dispensed to patients only in certain healthcare settings, specifically clinics, medical offices and hospitals by or under the supervision of a certified prescriber Further information is available at 1-855-MIFEINFO (1-855-643-3463). 5.4 Ectopic Pregnancy Mifepristone tablets, 200mg is contraindicated in patients with a confirmed or suspected ectopic pregnancy because mifepristone is not effective for terminating ectopic pregnancies [see Contraindications (4)]. Healthcare providers should remain alert to the possibility that a patient who is undergoing a medical abortion could have an undiagnosed ectopic pregnancy because some of the expected symptoms experienced with a medical abortion (abdominal pain, uterine bleeding) may be similar to those of a ruptured ectopic pregnancy. The presence of an ectopic pregnancy may have been missed even if the patient underwent ultrasonography prior to being prescribed Mifepristone tablets, 200mg. Women who became pregnant with an IUD in place should be assessed for ectopic pregnancy. 5.5 Rhesus Immunization The use of Mifepristone tablets, 200mg is assumed to require the same preventive measures as those taken prior to and during surgical abortion to prevent rhesus immunization.

6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Infection and sepsis [see Warnings and Precautions (5.1)] Uterine bleeding [see Warnings and Precautions (5.2)] 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Information presented on common adverse reactions relies solely on data from US studies, because rates reported in non-US studies were markedly lower and are not likely generalizable to the US population. In three US clinical studies totaling 1,248 women through 70 days gestation who used mifepristone 200mg orally followed 24-48 hours later by misoprostol 800mcg buccally, women reported adverse reactions in diaries and in interviews at the follow-up visit. These studies enrolled generally healthy women of reproductive age without contraindications to mifepristone or misoprostol use according to the Mifepristone tablets, 200mg product label.Gestational age was assessed prior to study enrollment using the date of the woman's last menstrual period, clinical evaluation, and/or ultrasound examination. About 85% of patients report at least one adverse reaction following administration of Mifepristone tablets, 200mg and misoprostol, and many can be expected to report more than one such reaction. The most commonly reported adverse reactions (>15%) were nausea, weakness, fever/chills, vomiting, headache, diarrhea, and dizziness (see Table 1). The frequency of adverse reactions varies between studies and may be dependent on many factors including the patient population and gestational age. Abdominal pain/cramping is expected in all medical abortion patients and its incidence is not reported in clinical studies. Treatment with Mifepristone tablets, 200mg and misoprostol is designed to induce uterine bleeding and cramping to cause termination of an intrauterine pregnancy. Uterine bleeding and cramping are expected consequences of the action of Mifepristone tablets, 200mg and misoprostol as used in the treatment procedure. Most women can expect bleeding more heavily than they do during a heavy menstrual period [see Warnings and Precautions (5.2)]. Table 1 lists the adverse reactions reported in US clinical studies with incidence >15% of women. Table 1 Adverse Reactions Reported in Women Following Administration of Mifepristone (oral) and Misoprostol (buccal) in US Clinical Studies Adverse Reaction # US studies Number of Evaluable Women Range of frequency (%) Upper Gestational Age of Studies Reporting Outcome Nausea 3 1,248 51-75% 70 days Weakness 2 630 55-58% 63 days Fever/chills 1 414 48% 63 days Vomiting 3 1,248 37-48% 70 days Headache 2 630 41-44% 63 days Diarrhea 3 1,248 18-43% 70 days Dizziness 2 630 39-41% 63 days One study provided gestational-age stratified adverse reaction rates for women who were 57-63 and 64-70 days; there was little difference in frequency of the reported common adverse reactions by gestational age. Information on serious adverse reactions was reported in six US and four non-US clinical studies, totaling 30,966 women through 70 days gestation who used mifepristone 200mg orally followed 24-48 hours later by misoprostol 800mcg buccally. Serious adverse reaction rates were similar between US and non-US studies, so rates from both US and non-US studies are presented. In the US studies, one studied women through 56 days gestation, four through 63 days gestation, and one through 70 days gestation, while in the non-US studies, two studied women through 63 days gestation, and two through 70 days gestation. Serious adverse reactions were reported in <0.5% of women. Information from the US and non-US studies is presented in Table 2. Table 2 Serious Adverse Reactions Reported in Women Following Administration of Mifepristone (oral) and Misoprostol (buccal) in US and Non-US Clinical Studies US Non-US Adverse Reaction # of studies Number of Evaluable Women Range of Frequency (%) # of studies Number of Evaluable Women Range of Frequency (%) Transfusion 4 17,774 0.03-0.5% 3 12,134 0-0.1% Sepsis 1 629 0.2% 1 11,155 <0.01%* ER visit 2 1,043 2.9-4.6% 1 95 0 Hospitalization Related to Medical Abortion 3 14,339 0.04-0.6% 3 1,286 0-0.7% Infection without sepsis 1 216 0 1 11,155 0.2% Hemorrhage NR NR NR 1 11,155 0.1% NR = Not reported *This outcome represents a single patient who experienced death related to sepsis. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of Mifepristone tablets, 200mg and misoprostol. 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. Infections and infestations : post-abortal infection (including endometritis, endomyometritis, parametritis, pelvic infection, pelvic inflammatory disease, salpingitis) Blood and the lymphatic system disorders : anemia Immune system disorders : allergic reaction (including anaphylaxis, angioedema, hives, rash, itching) Psychiatric disorders : anxiety Cardiac disorders : tachycardia (including racing pulse, heart palpitations, heart pounding) Vascular disorders : syncope, fainting, loss of consciousness, hypotension (including orthostatic), light-headedness Respiratory, thoracic and mediastinal disorders : shortness of breath Gastrointestinal disorders : dyspepsia Musculoskeletal, connective tissue and bone disorders : back pain, leg pain Reproductive system and breast disorders : uterine rupture, ruptured ectopic pregnancy, hematometra, leukorrhea General disorders and administration site conditions : pain

<table border="0" width="100%"><caption>Table 1 Adverse Reactions Reported in Women Following Administration of Mifepristone (oral) and Misoprostol (buccal) in US Clinical Studies</caption><tbody><tr><td>Adverse Reaction</td><td># US studies</td><td>Number of Evaluable Women</td><td>Range of frequency (%)</td><td>Upper Gestational Age of Studies Reporting Outcome</td></tr><tr><td>Nausea</td><td>3</td><td>1,248</td><td>51-75%</td><td>70 days</td></tr><tr><td>Weakness</td><td>2</td><td>630</td><td>55-58%</td><td>63 days</td></tr><tr><td>Fever/chills</td><td>1</td><td>414</td><td>48%</td><td>63 days</td></tr><tr><td>Vomiting</td><td>3</td><td>1,248</td><td>37-48%</td><td>70 days</td></tr><tr><td>Headache</td><td>2</td><td>630</td><td>41-44%</td><td>63 days</td></tr><tr><td>Diarrhea</td><td>3</td><td>1,248</td><td>18-43%</td><td>70 days</td></tr><tr><td>Dizziness</td><td>2</td><td>630</td><td>39-41%</td><td>63 days</td></tr></tbody></table>

<table border="0" width="100%"><caption>Table 2 Serious Adverse Reactions Reported in Women Following Administration of Mifepristone (oral) and Misoprostol (buccal) in US and Non-US Clinical Studies</caption><tbody><tr><td/><td>US</td><td colspan="5" rowspan="1">Non-US</td></tr><tr><td>Adverse Reaction</td><td># of studies</td><td>Number of Evaluable Women</td><td>Range of Frequency (%)</td><td># of studies</td><td>Number of Evaluable Women</td><td>Range of Frequency (%)</td></tr><tr><td>Transfusion</td><td>4</td><td>17,774</td><td>0.03-0.5%</td><td>3</td><td>12,134</td><td>0-0.1%</td></tr><tr><td>Sepsis</td><td>1</td><td>629</td><td>0.2%</td><td>1</td><td>11,155</td><td>&lt;0.01%*</td></tr><tr><td>ER visit</td><td>2</td><td>1,043</td><td>2.9-4.6%</td><td>1</td><td>95</td><td>0</td></tr><tr><td>Hospitalization Related to Medical Abortion</td><td>3</td><td>14,339</td><td>0.04-0.6%</td><td>3</td><td>1,286</td><td>0-0.7%</td></tr><tr><td>Infection without sepsis</td><td>1</td><td>216</td><td>0</td><td>1</td><td>11,155</td><td>0.2%</td></tr><tr><td>Hemorrhage</td><td>NR</td><td>NR</td><td>NR</td><td>1</td><td>11,155</td><td><paragraph>0.1%</paragraph></td></tr><tr><td colspan="7"><paragraph>NR = Not reported</paragraph><paragraph>*This outcome represents a single patient who experienced death related to sepsis.</paragraph></td></tr></tbody></table>