Usual Adult Dose for Abortion

Brand MIFEPREX:

• Day One: 200 mg mifepristone (MIFEPREX) orally as a single dose
• Day Two or Three: 800 mcg misoprostol buccally 24 to 48 hours after the first dose of mifepristone (Two 200 mcg misoprostol tablets should be placed in each cheek pouch [the area between the cheek and gums] for 30 minutes and then swallow any remnants with water or another liquid).

Post-treatment Assessment Day 7 to 14:

• A follow-up visit approximately 7 to 14 days after the administration of mifepristone is necessary to confirm complete termination of pregnancy and to evaluate the degree of bleeding.
• Termination of pregnancy can be confirmed by medical history, clinical examination, human Chorionic Gonadotropin (hCG) testing, or ultrasonographic scan. Lack of bleeding following treatment usually indicates failure; however, prolonged or heavy bleeding is not proof of a complete abortion.
• The existence of debris in the uterus (e.g., if seen on ultrasonography) following the treatment procedure will not necessarily require surgery for its removal.
• Patients should expect to experience vaginal bleeding or spotting for an average of 9 to 16 days. Heavy bleeding for a median duration of 2 days has been reported. Some women may experience some type of bleeding for more than 30 days. Persistence of heavy or moderate vaginal bleeding at the time of follow-up, however, could indicate an incomplete abortion.
• If complete expulsion has not occurred, but the pregnancy is not ongoing, another dose of misoprostol 800 mcg buccally may be administered. A follow-up visit in approximately 7 days to assess for complete termination is recommended.
• Surgical evacuation is recommended to manage ongoing pregnancies after medical abortion.

Comments.

• Medication for cramps or gastrointestinal symptoms may be needed during the period immediately following the administration of misoprostol.
• The effectiveness of the regimen may be lower if misoprostol is administered less than 24 hours or more than 48 hours after mifepristone (MIFEPREX) administration.
• Most women will expel the pregnancy within 2 to 24 hours of taking misoprostol; select appropriate location for the patient to be when misoprostol is administered, taking into account that expulsion could begin within 2 hours of administration.
• For purposes of this treatment (pregnancy termination), pregnancy is dated from the first day of the last menstrual period.
• The duration of pregnancy may be determined from menstrual history and clinical examination.
• Assess the pregnancy by ultrasonographic scan if the duration of pregnancy is uncertain or if ectopic pregnancy is suspected.
• Remove any intrauterine device (IUD) before beginning treatment with this drug.

Use: Medical termination of intrauterine pregnancy through 70 days gestation

Usual Adult Dose for Cushing's Syndrome

Brand KORLYM:
Initial dose: 300 mg orally once a day
Maximum dose: 1200 mg or 20 mg/kg once a day

Comments:

• Dose increases should occur once every 2 to 4 weeks. For additional information of dose titration refer to the Dose Adjustment section.

Use: Control of hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery

Usual Pediatric Dose for Abortion

Brand MIFEPREX:

• Day One: 200 mg mifepristone (MIFEPREX) orally as a single dose
• Day Two or Three: 800 mcg misoprostol buccally 24 to 48 hours after the first dose of mifepristone (Two 200 mcg misoprostol tablets should be placed in each cheek pouch [the area between the cheek and gums] for 30 minutes and then swallow any remnants with water or another liquid).

Post-treatment Assessment Day 7 to 14:

• A follow-up visit approximately 7 to 14 days after the administration of mifepristone is necessary to confirm complete termination of pregnancy and to evaluate the degree of bleeding.
• Termination of pregnancy can be confirmed by medical history, clinical examination, human Chorionic Gonadotropin (hCG) testing, or ultrasonographic scan. Lack of bleeding following treatment usually indicates failure; however, prolonged or heavy bleeding is not proof of a complete abortion.
• The existence of debris in the uterus (e.g., if seen on ultrasonography) following the treatment procedure will not necessarily require surgery for its removal.
• Patients should expect to experience vaginal bleeding or spotting for an average of 9 to 16 days. Heavy bleeding for a median duration of 2 days has been reported. Some women may experience some type of bleeding for more than 30 days. Persistence of heavy or moderate vaginal bleeding at the time of follow-up, however, could indicate an incomplete abortion.
• If complete expulsion has not occurred, but the pregnancy is not ongoing, another dose of misoprostol 800 mcg buccally may be administered. A follow-up visit in approximately 7 days to assess for complete termination is recommended.
• Surgical evacuation is recommended to manage ongoing pregnancies after medical abortion.

Comments.

• Medication for cramps or gastrointestinal symptoms may be needed during the period immediately following the administration of misoprostol.
• The effectiveness of the regimen may be lower if misoprostol is administered less than 24 hours or more than 48 hours after mifepristone (MIFEPREX) administration.
• Most women will expel the pregnancy within 2 to 24 hours of taking misoprostol; select appropriate location for the patient to be when misoprostol is administered, taking into account that expulsion could begin within 2 hours of administration.
• For purposes of this treatment (pregnancy termination), pregnancy is dated from the first day of the last menstrual period.
• The duration of pregnancy may be determined from menstrual history and clinical examination.
• Assess the pregnancy by ultrasonographic scan if the duration of pregnancy is uncertain or if ectopic pregnancy is suspected.
• Remove any intrauterine device (IUD) before beginning treatment with this drug.

Use: Medical termination of intrauterine pregnancy through 70 days gestation

Renal Dose Adjustments

Brand KORLYM: The maximum dose should not exceed 600 mg per day in renally impaired patients.

Brand MIFEPREX: Data not available

Liver Dose Adjustments

Brand KORLYM:

• Mild to moderate liver dysfunction: The maximum dose should not exceed 600 mg per day.
• Severe liver dysfunction: Not recommended

Brand MIFEPREX: Data not available

Dose Adjustments

Brand KORLYM:

• Dose increases should be based on tolerability and degree of improvement in Cushing's syndrome manifestations.
• Changes in glucose control, anti-diabetic medication requirements, insulin levels, and psychiatric symptoms may provide an early assessment of response (within 6 weeks) and may help guide early dose titration.
• Improvements in cushingoid appearance, acne, hirsutism, striae, and body weight occur over a longer period of time and, along with measures of glucose control, may be used to determine dose changes beyond the first 2 months of therapy.
• Careful and gradual titration of KORYLIM accompanied by monitoring for recognized adverse reactions may reduce the risk of severe adverse reactions.
• Dose reduction or even dose discontinuation may be needed in some clinical situations. If treatment is interrupted, it should be reinitiated at the lowest dose (300 mg). If treatment was interrupted because of adverse reactions, the titration should aim for a dose lower than the one that resulted in treatment interruption.
• If combination with strong CYP450 3A inhibitors is necessary, the dose should be limited to 300 mg per day.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Mifepristone (Brand MIFEPREX). It includes a medication guide, elements to assure safe use, and an implementation system. For additional information: www.fda.gov/REMS

US BOXED WARNINGS:
Brand MIFEPREX:
Serious and sometimes fatal infections and bleeding occur very rarely following spontaneous, surgical, and medical abortions, including following the use of this drug. No causal relationship between the use of this drug and misoprostol and these events has been established.

• Atypical Presentation of Infection: Patients with serious bacterial infections (e.g., Clostridium sordellii) and sepsis can present without fever, bacteremia, or significant findings on pelvic examination following an abortion. 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.
• Bleeding: Prolonged heavy bleeding may be a sign of incomplete abortion or other complications and prompt medical or surgical intervention may be needed. Advise patients to seek immediate medical attention if they experience prolonged heavy

vaginal bleeding. Before prescribing , inform the patient about the risk of these serious events. Ensure that the patient knows whom to call and what to do, including going to an Emergency Room if none of the provided contacts are reachable, if she experiences sustained fever, severe abdominal pain, prolonged heavy bleeding, or syncope, or if she experiences abdominal pain or discomfort, or general malaise (including weakness, nausea, vomiting or diarrhea) 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 a healthcare provider who did not prescribe MIFEPREX, so that the provider knows that she is undergoing a medical abortion.

Brand KORLYM:
Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone and glucocorticoid (GR-II) receptors, respectively. The antiprogestational effects will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with KORLYM and prevented during treatment and for one month after stopping treatment by the use of a non-hormonal medically acceptable method of contraception unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Pregnancy must also be excluded if treatment is interrupted for more than 14
days in females of reproductive potential.

Brand KORLYM: Safety and efficacy have not been established in patients younger than 18 years.

Brand MIFEPREX: Safety and efficacy in females patients younger than 17 years is similar to that observed in adults.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
Brand KORLYM:

• Tablets should be taken with a meal and should be swallowed whole. Do not split, crush, or chew tablets.

Brand MIFEPREX:

• Provide instructions to patients on what to do if significant discomfort, excessive vaginal bleeding or other adverse reactions occur.
• Advise the patient whether you will provide such care or will refer her to another provider as part of counseling prior to prescribing MIFEPREX.

Limitation of Use:
Brand KORLYM should not be used in the treatment of patients with type 2 diabetes unless it is secondary to Cushing's syndrome.

Monitoring:
Brand KORLYM:

• Endocrine: Adrenal insufficiency
• Metabolic: Hypokalemia

Brand MIFEPREX:

• Genitourinary: Persistent vaginal bleeding
• Immunologic: Infection

Patient advice:

• Brand MIFEPREX: Patients should seek immediate medical attention if they experience prolonged heavy vaginal bleeding.