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 )] Most common adverse reactions (>15%) are nausea, weakness, fever/chills, vomiting, headache, diarrhea, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact GenBioPro, Inc. at 1-855-643-3463 or medical@genbiopro.com or www.MIFEINFO.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 200 mg 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, 200 mg 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, 200 mg 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, 200 mg 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, 200 mg and misoprostol as used in the treatment procedure.
Most patients 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 NR= Not reported * This outcome represents a single patient who experienced death related to sepsis. Adverse Reaction US Non-US # 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%
6.2Postmarketing Experience
The following adverse reactions have been identified during post approval use of Mifepristone tablets, 200 mg 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
