MIFEPREX™ (mifepristone) Tablets, 200 mg
`For Oral Administration Only
`
`If Mifeprex* results in incomplete abortion, surgical intervention may be necessary.
`Prescribers should determine in advance whether they will provide such care themselves
`or through other providers. Prescribers should also give patients clear instructions on
`whom to call and what to do in the event of an emergency following administration of
`Mifeprex.
`
`Prescribers should make sure that patients receive and have an opportunity to discuss the
`Medication Guide and the PATIENT AGREEMENT.
`
`DESCRIPTION
`
`Mifeprex tablets each contain 200 mg of mifepristone, a synthetic steroid with
`antiprogestational effects. The tablets are light yellow in color, cylindrical and biconvex,
`and are intended for oral administration only. The tablets include the inactive ingredients
`colloidal silica anhydrous, corn starch, povidone, microcrystalline cellulose, and
`magnesium stearate.
`
`Mifepristone is a substituted 19-nor steroid compound chemically designated as 11ß-[p-
`(Dimethylamino)phenyl]-17ß-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one. Its
`empirical formula is C29H35NO2. Its structural formula is:
`
`The compound is a yellow powder with a molecular weight of 429.6 and a melting point
`of 191-196°C. It is very soluble in methanol, chloroform and acetone and poorly soluble
`in water, hexane and isopropyl ether.
`
`* Mifeprex is a trademark of Danco Laboratories, LLC.
`
`

`

`CLINICAL PHARMACOLOGY
`
`Pharmacodynamic Activity
`
`The anti-progestational activity of mifepristone results from competitive interaction with
`progesterone at progesterone-receptor sites. Based on studies with various oral doses in
`several animal species (mouse, rat, rabbit and monkey), the compound inhibits the
`activity of endogenous or exogenous progesterone. The termination of pregnancy results.
`
`Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the
`endometrial and myometrial effects of progesterone in women. During pregnancy, the
`compound sensitizes the myometrium to the contraction-inducing activity of
`prostaglandins.
`
`Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The
`activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10
`to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a
`compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.
`Antiandrogenic activity was observed in rats following repeated administration of doses
`from 10 to 100 mg/kg.
`
`Pharmacokinetics and Metabolism
`
`Absorption
`
`Following oral administration of a single dose of 600 mg, mifepristone is rapidly
`absorbed, with a peak plasma concentration of 1.98 mg/l occurring approximately 90
`minutes after ingestion. The absolute bioavailability of a 20 mg oral dose is 69%.
`
`Distribution
`
`Mifepristone is 98% bound to plasma proteins, albumin and α1-acid glycoprotein.
`Binding to the latter protein is saturable, and the drug displays nonlinear kinetics with
`respect to plasma concentration and clearance. Following a distribution phase,
`elimination of mifepristone is slow at first (50% eliminated between 12 and 72 hours) and
`then becomes more rapid with a terminal elimination half-life of 18 hours.
`
`

`

`Metabolism
`
` Metabolism of mifepristone is primarily via pathways involving N-demethylation and
`terminal hydroxylation of the 17-propynyl chain. In vitro studies have shown that
`CYP450 3A4 is primarily responsible for the metabolism. The three major metabolites
`identified in humans are: (1) RU 42 633, the most widely found in plasma, is the N-
`monodemethylated metabolite; (2) RU 42 848, which results from the loss of two methyl
`groups from the 4-dimethylaminophenyl in position 11ß; and (3) RU 42 698, which
`results from terminal hydroxylation of the 17-propynyl chain.
`
`Excretion
`
`By 11 days after a 600 mg dose of tritiated compound, 83% of the drug has been
`accounted for by the feces and 9% by the urine. Serum levels are undetectable by 11
`days.
`
`Special Populations
`
`The effects of age, hepatic disease and renal disease on the safety, efficacy and
`pharmacokinetics of mifepristone have not been investigated.
`
`Clinical Studies
`
`Safety and efficacy data from the U.S. clinical trials and from two French trials of
`mifepristone are reported below. The U.S. trials provide safety data on 859 women and
`efficacy data on 827 women with gestation durations of 49 days or less (dated from the
`first day of the last menstrual period). In the two French clinical trials, safety evaluable
`data are available for 1800 women, while efficacy information is available for 1681 of
`these women. Success was defined as the complete expulsion of the products of
`conception without the need for surgical intervention. The overall rates of success and
`failure, shown by reason for failure, for the U.S. and French studies appear in Table 1.
`
`In the U.S. trials, 92.1% of the 827 subjects had a complete medical abortion, as shown in
`Table 1. In 52 women (6.3%) expulsion occurred within two days, and resulted from the
`action of mifepristone (600 mg) alone, unaided by misoprostol, an analog of
`prostaglandin E2. All other women without an apparent expulsion took a 400 µg dose of
`misoprostol two days after taking mifepristone. Many women (44.1%) in the U.S. trials
`expelled the products of conception within four hours after taking misoprostol and 62.8%
`experienced expulsion within 24 hours after the misoprostol administration. There were
`65 women (7.9%) who received surgical interventions: 13 (1.6%) were medically
`indicated interventions during the study period, mostly for excessive bleeding; five
`(0.6%) interventions occurred at the patient’s request; 39 women (4.7%) had incomplete
`abortions at the end of the study protocol; and eight (1.0%) had ongoing pregnancies at
`the end of the study protocol.
`
`

`

`Women who participated in the U.S. trials reflect the racial and ethnic composition of
`American women. The majority of women (71.4%) were Caucasian, while 11.3% were
`African American, 10.9% were East Asian, and 4.7% were Hispanic. A small percentage
`(1.7%) belonged to other racial or ethnic groups. Women aged 18 to 45 were enrolled in
`the trials. Nearly two-thirds (66.0%) of the women were under 30 years old with a mean
`age of 27 years.
`
`In the French trials, complete medical abortion occurred in 95.5% of the 1681 subjects, as
`shown in Table 1. In 89 women (5.3%), complete abortion occurred within two days of
`taking mifepristone (600 mg). About half of the women (50.3%) in the French trials
`expelled the products of conception during the first four hours immediately following
`administration of misoprostol and 72.3% experienced expulsion within 24 hours after
`taking misoprostol. In total, 4.5% of women in the French trials ultimately received
`surgical intervention for excessive bleeding, incomplete abortions, or ongoing
`pregnancies at the end of the protocol.
`
`

`

`Table 1
`
`Outcome Following
`Treatment with Mifepristone and Misoprostol in the U.S. and French Trials
`
`Complete medical abortion
`Timing of expulsion
`
`Before second visit
`
`During second visit
`–
`less than 4 hrs after misoprostol
`
`After second visit
`– greater than 4 hrs but less than 24 hrs
`after misoprostol
`– greater than 24 hrs after misoprostol
`
`Time of expulsion unknown
`
`Surgical intervention
`Reason for surgery
`
`U.S. Trials
`
`French Trials
`
`N
`
`762
`
`%
`
`92.1
`
`N
`
`1605
`
`%
`
`95.5
`
`52
`
`(6.3)
`
`89
`
`(5.3)
`
`365
`
`(44.1)
`
`846
`
`(50.3)
`
`155
`68
`
`122
`
`(18.7)
`(8.2)
`
`(14.8)
`
`370
`145
`
`155
`
`(22.0)
`(8.6)
`
`(9.2)
`
`65
`
`7.9
`
`76
`
`4.5
`
`Medically necessary interventions during
`the study period
`Patient request
`Treatment of bleeding during study
`Incomplete expulsion at study end
`Ongoing pregnancy at study end
`
`13
`5
`NA
`39
`8
`
`(1.6)
`(0.6)
`(NA)
`(4.7)
`(1.0)
`
`NA
`NA
`6
`48
`22
`
`(NA)
`(NA)
`(0.3)
`(2.9)
`(1.3)
`
`Total
`
`827
`
`100
`
`1681
`
`100
`
`Note: Mifepristone 600 mg oral was administered on Day 1, misoprostol 400 µg oral
`was given on Day 3 (second visit).
`
`

`

`INDICATION AND USAGE
`
`Mifeprex is indicated for the medical termination of intrauterine pregnancy through 49
`days’ pregnancy. For purposes of this treatment, pregnancy is dated from the first day of
`the last menstrual period in a presumed 28 day cycle with ovulation occurring at mid-
`cycle. The duration of pregnancy may be determined from menstrual history and by
`clinical examination. Ultrasonographic scan should be used if the duration of pregnancy
`is uncertain, or if ectopic pregnancy is suspected.
`
`Any intrauterine device (“IUD”) should be removed before treatment with Mifeprex
`begins.
`
`Patients taking Mifeprex must take 400 µg of misoprostol two days after taking
`mifepristone unless a complete abortion has already been confirmed before that time (see
`DOSAGE AND ADMINISTRATION).
`
`Pregnancy termination by surgery is recommended in cases when Mifeprex and
`misoprostol fail to cause termination of intrauterine pregnancy (see PRECAUTIONS).
`
`CONTRAINDICATIONS
`
`Administration of Mifeprex and misoprostol for the termination of pregnancy (the
`“treatment procedure”) is contraindicated in patients with any one of the following
`conditions:
`
`- Confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass (the
`treatment procedure will not be effective to terminate an ectopic pregnancy);
`IUD in place (see INDICATION AND USAGE);
`-
`- Chronic adrenal failure;
`- Concurrent long-term corticosteroid therapy;
`- History of allergy to mifepristone, misoprostol or other prostaglandin;
`- Hemorrhagic disorders or concurrent anticoagulant therapy;
`-
`Inherited porphyrias.
`
`Because it is important to have access to appropriate medical care if an emergency
`develops, the treatment procedure is contraindicated if a patient does not have adequate
`access to medical facilities equipped to provide emergency treatment of incomplete
`abortion, blood transfusions, and emergency resuscitation during the period from the first
`visit until discharged by the administering physician.
`
`Mifeprex also should not be used by any patient who may be unable to understand the
`effects of the treatment procedure or to comply with its regimen. Patients should be
`instructed to review the Medication Guide and the PATIENT AGREEMENT provided
`with Mifeprex carefully and should be given a copy of the product label for their review.
`
`

`

`Patients should discuss their understanding of these materials with their health care
`providers, and retain the Medication Guide for later reference (see PRECAUTIONS).
`
`WARNINGS
`(see CONTRAINDICATIONS)
`
`1. Bleeding
`
`Vaginal bleeding occurs in almost all patients during the treatment procedure. According
`to data from the U.S. and French trials, women should expect to experience bleeding or
`spotting for an average of nine to 16 days, while up to 8% of all subjects may experience
`some type of bleeding for 30 days or more. Bleeding was reported to last for 69 days in
`one patient in the French trials. In general the duration of bleeding and spotting increased
`as the duration of the pregnancy increased.
`
`In some cases, excessive bleeding may require treatment by vasoconstrictor drugs,
`curettage, administration of saline infusions, and/or blood transfusions. In the U.S. trials,
`4.8% of subjects received administration of uterotonic medications and nine women
`(1.0%) received intravenous fluids. Vasoconstrictor drugs were used in 4.3% of all
`subjects in the French trials, and in 5.5% of women there was a decrease in hemoglobin
`of more than 2 g/dL. Blood transfusions were administered in one of 859 subjects in the
`U.S. trials and in two of 1800 subjects in the French trials. Since heavy bleeding
`requiring curettage occurs in about 1% of patients, special care should be given to
`patients with hemostatic disorders, hypocoagulability, or severe anemia.
`
`2. Confirmation of Pregnancy Termination
`
`Patients should be scheduled for and return for a follow-up visit at approximately 14 days
`after administration of mifepristone to confirm that the pregnancy is completely
`terminated and to assess the degree of bleeding. Vaginal bleeding is not evidence of the
`termination of pregnancy. Termination can be confirmed by clinical examination or
`ultrasonographic scan. Lack of bleeding following treatment, however, usually indicates
`failure. Medical abortion failures should be managed with surgical termination.
`
`PRECAUTIONS
`
`General
`
`Mifeprex is available only in single dose packaging. Administration must be under the
`supervision of a qualified physician (see DOSAGE AND ADMINISTRATION).
`
`The use of Mifeprex is assumed to require the same preventive measures as those taken
`prior to and during surgical abortion to prevent rhesus immunization.
`
`There are no data on the safety and efficacy of mifepristone in women with chronic
`medical conditions such as cardiovascular, hypertensive, hepatic, respiratory or renal
`
`

`

`disease; insulin-dependent diabetes mellitus; severe anemia or heavy smoking. Women
`who are more than 35 years of age and who also smoke 10 or more cigarettes per day
`should be treated with caution because such patients were generally excluded from
`clinical trials of mifepristone.
`
`Although there is no clinical evidence, the effectiveness of Mifeprex may be lower if
`misoprostol is administered more than two days after mifepristone administration.
`
`Information for Patients
`
`Patients should be fully advised of the treatment procedure and its effects. Patients
`should be given a copy of the Medication Guide and the PATIENT AGREEMENT.
`(Additional copies of the Medication Guide and the PATIENT AGREEMENT are
`available by contacting Danco Laboratories at 1-877-4 Early Option) (1-877-432-7596).
`Patients should be advised to review both the Medication Guide and the PATIENT
`AGREEMENT, and should be given the opportunity to discuss them and obtain answers
`to any questions they may have. Each patient must understand:
`
`-
`
`-
`-
`-
`-
`-
`
`the necessity of completing the treatment schedule, including a follow-up visit
`approximately 14 days after taking Mifeprex;
`that vaginal bleeding and uterine cramping probably will occur;
`that prolonged or heavy vaginal bleeding is not proof of a complete expulsion;
`that if the treatment fails, there is a risk of fetal malformation;
`that medical abortion treatment failures are managed by surgical termination; and
`the steps to take in an emergency situation, including precise instructions and a
`telephone number that she can call if she has any problems or concerns.
`
`Another pregnancy can occur following termination of pregnancy and before resumption
`of normal menses. Contraception can be initiated as soon as the termination of the
`pregnancy has been confirmed, or before the woman resumes sexual intercourse.
`
`Patient information is included with each package of Mifeprex (see Medication Guide).
`
`Laboratory Tests
`
`Clinical examination is necessary to confirm the complete termination of pregnancy after
`the treatment procedure. Changes in quantitative human Chorionic Gonadotropin (hCG)
`levels will not be decisive until at least 10 days after the administration of Mifeprex. A
`continuing pregnancy can be confirmed by ultrasonographic scan.
`
`The existence of debris in the uterus following the treatment procedure will not
`necessarily require surgery for its removal.
`
`Decreases in hemoglobin concentration, hematocrit and red blood cell count occur in
`some women who bleed heavily. Hemoglobin decreases of more than 2 g/dL occurred in
`5.5% of subjects during the French clinical trials of mifepristone and misoprostol.
`
`

`

`Clinically significant changes in serum enzyme (serum glutamic oxaloacetic
`transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline
`phosphatase, gamma-glutamyltransferase (GT)) activities were rarely reported.
`
`Drug Interactions
`
`Although specific drug or food interactions with mifepristone have not been studied, on
`the basis of this drug’s metabolism by CYP 3A4, it is possible that ketoconazole,
`itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing
`serum levels of mifepristone). Furthermore, rifampin, dexamethasone, St. John’s Wort,
`and certain anticonvulsants (phenytoin, phenobarbital, carbamazepine) may induce
`mifepristone metabolism (lowering serum levels of mifepristone).
`
`Based on in vitro inhibition information, coadministration of mifepristone may lead to an
`increase in serum levels of drugs that are CYP 3A4 substrates. Due to the slow
`elimination of mifepristone from the body, such interaction may be observed for a
`prolonged period after its administration. Therefore, caution should be exercised when
`mifepristone is administered with drugs that are CYP 3A4 substrates and have narrow
`therapeutic range, including some agents used during general anesthesia.
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`No long-term studies to evaluate the carcinogenic potential of mifepristone have been
`performed. Results from studies conducted in vitro and in animals have revealed no
`genotoxic potential for mifepristone. Among the tests carried out were: Ames test with
`and without metabolic activation; gene conversion test in Saccharomyces cerevisiae D4
`cells; forward mutation in Schizosaccharomyces pompe P1 cells; induction of
`unscheduled DNA synthesis in cultured HeLa cells; induction of chromosome aberrations
`in CHO cells; in vitro test for gene mutation in V79 Chinese hamster lung cells; and
`micronucleus test in mice.
`
`The pharmacological activity of mifepristone disrupts the estrus cycle of animals,
`precluding studies designed to assess effects on fertility during drug administration.
`Three studies have been performed in rats to determine whether there were residual
`effects on reproductive function after termination of the drug exposure.
`
`In rats, administration of the lowest oral dose of 0.3 mg/kg/day caused severe disruption
`of the estrus cycles for the three weeks of the treatment period. Following resumption of
`the estrus cycle, animals were mated and no effect on reproductive performance was
`observed. In a neonatal exposure study in rats, the administration of a subcutaneous dose
`of mifepristone up to 100 mg/kg on the first day after birth had no adverse effect on
`future reproductive function in males or females. The onset of puberty was observed to
`be slightly premature in female rats neonatally exposed to mifepristone. In a separate
`study in rats, oviduct and ovary malformations in female rats, delayed male puberty,
`
`

`

`deficient male sexual behavior, reduced testicular size, and lowered ejaculation frequency
`were noted after exposure to mifepristone (1 mg every other day) as neonates.
`
`Pregnancy
`
`Mifepristone is indicated for use in the termination of pregnancy (through 49 days’
`pregnancy) and has no other approved indication for use during pregnancy.
`
`Teratogenic Effects
`
`Human Data
`
`Over 620,000 women in Europe have taken mifepristone in combination with a
`prostaglandin to terminate pregnancy. Among these 620,000 women, about 415,000
`have received mifepristone together with misoprostol. As of May 2000 a total of 82
`cases have been reported in which women with on-going pregnancies after using
`mifepristone alone or mifepristone followed by misoprostol declined to have a surgical
`procedure at that time. These cases are summarized in Table 2.
`
`Table 2
`
`Reported Cases (as of May 2000) of On-going Pregnancies Not Terminated by
`Surgical
`
`Abortion at the End of Treatment with Mifepristone Alone
`or with Mifepristone-Misoprostol
`
` Mifepristone Mifepristone- Total
` Alone
` Misoprostol
`
`10
`Subsequently had surgical abortion 3 7
` No abnormalities detected 2 7 9
` Abnormalities detected 1 0 1
` (sirenomelia, cleft palate)
`
`
`
`Subsequently resulted in live birth 13 13 26
` No abnormalities detected at birth 13 13 26
` Abnormalities detected at birth 0 0 0
`
`Other/Unknown 26 20 46
`
`Total 42 40 82
`
`

`

`Several reports in the literature indicate that prostaglandins, including misoprostol, may
`have teratogenic effects in human beings. Skull defects, cranial nerve palsies, delayed
`growth and psychomotor development, facial malformation and limb defects have all
`been reported after exposure during the first trimester.
`
`Animal Data
`
`Teratology studies in mice, rats and rabbits at doses of 0.25 to 4.0 mg/kg (less than 1/100
`to approximately 1/3 the human exposure level based on body surface area) were carried
`out. Because of the antiprogestational activity of mifepristone, fetal losses were much
`higher than in control animals. Skull deformities were detected in rabbit studies at
`approximately 1/6 the human exposure, although no teratogenic effects of mifepristone
`have been observed to date in rats or mice. These deformities were most likely due to the
`mechanical effects of uterine contractions resulting from decreased progesterone levels.
`
`Nonteratogenic Effects
`
`The indication for use of Mifeprex in conjunction with misoprostol is for the termination
`of pregnancy through 49 days' duration of pregnancy (as dated from the first day of the
`last menstrual period). These drugs together disrupt pregnancy by causing decidual
`necrosis, myometrial contractions and cervical softening, leading to the expulsion of the
`products of conception.
`
`

`

`Nursing Mothers
`
`It is not known whether mifepristone is excreted in human milk. Many hormones with a
`similar chemical structure, however, are excreted in breast milk. Since the effects of
`mifepristone on infants are unknown, breast-feeding women should consult with their
`health care provider to decide if they should discard their breast milk for a few days
`following administration of the medications.
`
`Pediatric Use
`
`Safety and effectiveness in pediatric patients have not been established.
`
`ADVERSE REACTIONS
`
`The treatment procedure is designed to induce the vaginal bleeding and uterine cramping
`necessary to produce an abortion. Nearly all of the women who receive Mifeprex and
`misoprostol will report adverse reactions, and many can be expected to report more than
`one such reaction. About 90% of patients report adverse reactions following
`administration of misoprostol on day three of the treatment procedure. Those adverse
`events that occurred with a frequency greater than 1% in the U.S. and French trials are
`shown in Table 3.
`
`Bleeding and cramping are expected consequences of the action of Mifeprex as used in
`the treatment procedure. Following administration of mifepristone and misoprostol in the
`French clinical studies, 80 to 90% of women reported bleeding more heavily than they do
`during a heavy menstrual period (see WARNINGS, Bleeding for additional information).
`Women also typically experience abdominal pain, including uterine cramping. Other
`commonly reported side effects were nausea, vomiting and diarrhea. Pelvic pain,
`fainting, headache, dizziness, and asthenia occurred rarely. Some adverse reactions
`reported during the four hours following administration of misoprostol were judged by
`women as being more severe than others: the percentage of women who considered any
`particular adverse event as severe ranged from 2 to 35% in the U.S. and French trials.
`After the third day of the treatment procedure, the number of reports of adverse reactions
`declined progressively in the French trials, so that by day 14, reports were rare except for
`reports of bleeding and spotting.
`
`

`

`Table 3
`
`Type of Reported Adverse Events Following Administration of
`Mifepristone and Misoprostol in the U.S. and French Trials* (percentages)
`
`U.S. Trials
`
`French Trials
`
`Abdominal Pain (cramping)
`Uterine cramping
`Nausea
`Headache
`Vomiting
`Diarrhea
`Dizziness
`Fatigue
`Back pain
`Uterine hemorrhage
`Fever
`Viral infections
`Vaginitis
`Rigors (chills/shaking)
`Dyspepsia
`Insomnia
`Asthenia
`Leg pain
`Anxiety
`Anemia
`Leukorrhea
`Sinusitis
`Syncope
`Decrease in hemoglobin greater than 2 g/dL
`Pelvic pain
`Fainting
`
`96
`NA
`61
`31
`26
`20
`12
`10
`9
`5
`4
`4
`3
`3
`3
`3
`2
`2
`2
`2
`2
`2
`1
`NA
`NA
`NA
`
`NA
`83
`43
`2
`18
`12
`1
`NA
`NA
`NA
`NA
`NA
`NA
`NA
`NA
`NA
`1
`NA
`NA
`NA
`NA
`NA
`NA
`6
`2
`2
`
`* Only adverse reactions with incidence >1% are included.
`
`OVERDOSAGE
`
`

`

`No serious adverse reactions were reported in tolerance studies in healthy non-pregnant
`female and healthy male subjects where mifepristone was administered in single doses
`greater than threefold that recommended for termination of pregnancy. If a patient
`ingests a massive overdose, she should be observed closely for signs of adrenal failure.
`
`The oral acute lethal dose of mifepristone in the mouse, rat and dog is greater than 1000
`mg/kg (about 100 times the human dose recommended for termination of pregnancy).
`
`DOSAGE AND ADMINISTRATION
`
`Treatment with Mifeprex and misoprostol for the termination of pregnancy requires three
`office visits by the patient. Mifeprex should be prescribed only by physicians who have
`read and understood the prescribing information. Mifeprex may be administered only in
`a clinic, medical office, or hospital, by or under the supervision of a physician, able to
`assess the gestational age of an embryo and to diagnose ectopic pregnancies. Physicians
`must also be able to provide surgical intervention in cases of incomplete abortion or
`severe bleeding, or have made plans to provide such care through others, and be able to
`assure patient access to medical facilities equipped to provide blood transfusions and
`resuscitation, if necessary.
`
`Day One: Mifeprex Administration
`
`Patients must read the Medication Guide and read and sign the PATIENT AGREEMENT
`before Mifeprex is administered.
`
`Three 200 mg tablets (600 mg) of Mifeprex are taken in a single oral dose.
`
`Day Three: Misoprostol Administration
`
`The patient returns to the healthcare provider two days after ingesting Mifeprex. Unless
`abortion has occurred and has been confirmed by clinical examination or
`ultrasonographic scan, the patient takes two 200 µg tablets (400 µg) of misoprostol
`orally.
`
`During the period immediately following the administration of misoprostol, the patient
`may need medication for cramps or gastrointestinal symptoms (see ADVERSE
`REACTIONS). The patient should be given instructions on what to do if significant
`discomfort, excessive bleeding or other adverse reactions occur and should be given a
`phone number to call if she has questions following the administration of the misoprostol.
`In addition, the name and phone number of the physician who will be handling
`emergencies should be provided to the patient.
`
`

`

`Day 14: Post-Treatment Examination
`
`Patients will return for a follow-up visit approximately 14 days after the administration of
`Mifeprex. This visit is very important to confirm by clinical examination or
`ultrasonographic scan that a complete termination of pregnancy has occurred.
`
`According to data from the U.S. and French studies, women should expect to experience
`bleeding or spotting for an average of nine to 16 days. Up to 8% of women may
`experience some type of bleeding for more than 30 days. Persistence of heavy or
`moderate vaginal bleeding at this visit, however, could indicate an incomplete abortion.
`
`Patients who have an ongoing pregnancy at this visit have a risk of fetal malformation
`resulting from the treatment. Surgical termination is recommended to manage medical
`abortion treatment failures (see PRECAUTIONS, Pregnancy).
`
`Adverse events, such as hospitalization, blood transfusion, ongoing pregnancy, or other
`major complications following the use of Mifeprex and misoprostol must be reported to
`Danco Laboratories. Please provide a brief clinical and administrative synopsis of any
`such adverse events in writing to:
`
`Medical Director
`Danco Laboratories, LLC
`P.O. Box 4816
`New York, NY 10185
`1-877-4-Early Option (1-877-432-7596)
`
`For immediate consultation 24 hours a day, 7 days a week with an expert in mifepristone,
`call Danco Laboratories at 1-877-4 Early Option (1-877-432-7596).
`
`HOW SUPPLIED
`
`Mifeprex will be supplied only to licensed physicians who sign and return a Prescriber’s
`Agreement. Distribution of Mifeprex will be subject to specific requirements imposed by
`the distributor, including procedures for storage, dosage tracking, damaged product
`returns and other matters. Mifeprex is a prescription drug, although it will not be
`available to the public through licensed pharmacies.
`
`Mifeprex is supplied as light yellow, cylindrical, bi-convex tablets imprinted on one side
`with “MF.” Each tablet contains 200 mg of mifepristone. Tablets are packaged in single
`dose blister packets containing three tablets and are supplied in individual cartons
`(National Drug Code 6487500103).
`
`Store at 250C (770F); excursions permitted to 15-300C (59-860F) [see USP Controlled
`Room Temperature].
`
`Manufactured for:
`
`

`

`Danco Laboratories, LLC
`P.O. Box 4816
`New York, NY 10185
`1-877-4 Early Option (1-877-432-7596)
`www.earlyoptionpill.com
`
`