Drug Information
Mifepristone Medication Guide
Mifepristone blocks the progesterone receptor, leading to changes in the endometrial blood supply. In contrast, methotrexate inhibits DNA synthesis and primarily affects rapidly dividing cells. In early pregnancy methotrexate interferes with the process of implantation through its effect on trophoblastic tissue. The net effect of mifepristone and methotrexate - detachment of the trophoblast from the uterine decidua - is the same. Mifepristone also softens the cervix to facilitate expulsion of the pregnancy. The prostaglandin analogue misoprostol accelerates the process of expulsion by stimulating uterine contractions as well as softening the cervix
Description
Mifepristone (mif-i-PRIS-tone)is used to end a pregnancy that is less than 49 days' in duration. It works by stopping the supply of hormones that maintains the interior of the uterus. Without these hormones, the uterus cannot support the pregnancy and the contents of the uterus are expelled.
Before Using This Medicine
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For mifepristone, the following should be considered:
Allergies-Tell your doctor if you have ever had any unusual or allergic reaction to mifepristone, misoprostol or any other prostaglandins.
Pregnancy-Mifepristone is used to terminate an early pregnancy. Fetal deformities may result if a pregnancy is allowed to continue following a failed attempt at medical termination.
Breast-feeding-It is unknown whether mifepristone is distributed in the breast milk.
Other medicines-Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking mifepristone, it is especially important that your doctor and pharmacist know if you are taking any of the following:
* Carbamazepine (e.g., Tegretol) or
* Dexamethasone (e.g., Decadron) or
* Phenobarbital (e.g., Luminal) or
* Phenytoin (e.g., Dilantin) or
* Rifampin (e.g., Rifadin) or
* St. John's Wort - May decrease the concentration of mifepristone in the blood
* Erythromycin (e.g., E-Mycin) or
* Grapefruit juice or
* Itraconazole (e.g., Sporanox) or
* Ketoconazole (e.g., Nizoral) - May increase the concentration of mifepristone in the blood
* Anticoagulants, such as warfarin (e.g., Coumadin) - May increase the risk of bleeding
* Corticosteroids (cortisone-like medicine)-Mifepristone may not work as well
Other medical problems-The presence of other medical problems may affect the use of mifepristone. Make sure you tell your doctor if you have any other medical problems, especially:
* Bleeding problems-May cause excessive vaginal bleeding
* Adrenal failure - Mifepristone may not work appropriately
* Ectopic pregnancy or
* Lower abdominal mass - Mifepristone will not terminate an ectopic pregnancy
* An intrauterine device (IUD) that is still in the uterus - Must be removed before mifepristone therapy is started
* Porphyria, inherited
* Anemia, severe or
* Poor blood circulation or
* Inability of blood to clot properly-Mifepristone causes heavy bleeding in a small portion of users, this may be intensified in patients with bleeding disorders
Proper Use of This Medicine
Dosing-
* To terminate a pregnancy of 49 days or less duration:
o For oral dosage form (tablets):
* Adults-600 milligrams (mg) (three 200 mg tablets) as a single oral dose followed two days later by 400 micrograms (mcg) (two 200 mcg tablets) of misoprostol as a single oral dose.
Precautions While Using This Medicine
You must have 3 visits to your physicians office during the treatment procedure. It is extremely important that you attend all three visits
Check with your physician if the vaginal bleeding becomes severe or seems to last longer than expected
You may need to have a surgical procedure to stop excessive vaginal bleeding or to terminate a pregnancy that was not terminated with the medical treatment procedure
Side Effects of This Medicine
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor as soon as possible if any of the following side effects occur:
Less common
Excessively heavy vaginal bleeding; unusual tiredness or weakness
Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome.
More Common
Abdominal pain or uterine cramping; back pain; diarrhea; dizziness; headache; nausea or vomiting
Less common
Acid or sour stomach; anxiety; belching ; cough; fainting or light-headedness when getting up from a lying or sitting position ; fever ; flu-like symptoms; headache; heartburn ; increased clear or white vaginal discharge; indigestion ; itching of the vagina or genital area; lack or loss of strength; pain during sexual intercourse; pain or tenderness around eyes and cheekbones; pale skin; shaking chills; shortness of breath or troubled breathing; sleeplessness or trouble sleeping ; stomach discomfort, upset, or pain; tightness of chest or wheezing; troubled breathing, exertional; unusual bleeding or bruising; stuffy or runny nose
Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.
Mifeprex (MIF-eh-prex)
(mifepristone)
Read this information carefully before taking Mifeprex and misoprostol. It will help you understand how the treatment works. This Medication Guide does not take the place of talking with your health care provider (provider).
What is the most important information I should know about Mifeprex?
Mifeprex is used to end an early pregnancy. It is not approved for ending later pregnancies. Early pregnancy means it is 49 days (7 weeks) or less since your last menstrual period began. By using Mifeprex, you probably will not need a surgical procedure to end your pregnancy.
When you use Mifeprex, you also need to take another medicine called misoprostol. You take misoprostol 2 days after you take Mifeprex.
You need to sign a statement (PATIENT AGREEMENT). Before you get Mifeprex, you will need to read and understand the information in this Medication Guide. Then you will need to sign a statement that you have decided to end your pregnancy.
You must visit your provider on Day 1, Day 3, and about Day 14. See the section called "How should I take Mifeprex?" for information about what happens at each visit. If you do not follow all the steps in "How should I take Mifeprex?" you will not know if your pregnancy has ended.
What to do if you are still pregnant after Mifeprex or Mifeprex with misoprostol treatment. If you are still pregnant, your provider will talk with you about the other choices you have, including a surgical procedure to end your pregnancy. There is a chance that there may be birth defects if the pregnancy is not ended.
Symptoms to expect. This treatment causes cramping and bleeding. Usually, these symptoms mean that the treatment is working. But sometimes you can get cramping and bleeding and still be pregnant. This is why you must return to your provider on Day 3 and about Day 14.
If you are not already bleeding after taking Mifeprex, you probably will begin to bleed once you take misoprostol. This is a medicine you take on Day 3. Bleeding or spotting can be expected for an average of 9-16 days and may last for up to 30 days. Your bleeding may be similar to, or greater than, a normal heavy period. You may see blood clots and tissue that come from your uterus. This is an expected part of ending the pregnancy.
Heavy bleeding and the need for surgery. In about 1 out of 100 women, bleeding can be so heavy that it requires a surgical procedure (curettage) to stop it. This is why you must talk with your provider about what to do if you need emergency care to stop heavy and possibly dangerous bleeding.
Before you take Mifeprex. Your provider will give you a telephone number to call if you have any questions, concerns, or problems. Your provider will also give you the name and phone number of who will handle emergencies.
Talk with your provider. You and your provider should discuss the benefits and risks for you of using Mifeprex.
What is Mifeprex?
Mifeprex blocks a hormone needed for your pregnancy to continue. When used together with another medicine called misoprostol, Mifeprex ends your pregnancy. About 5-8 out of 100 women taking Mifeprex will need a surgical procedure to end the pregnancy or to stop too much bleeding.
Who should not take Mifeprex?
Some women should not take Mifeprex. Do not take it if:
* It has been more than 49 days (7 weeks) since your last menstrual period began.
* You have an IUD. It must be taken out before you take Mifeprex.
* Your provider has told you that you have a pregnancy outside the uterus (ectopic pregnancy).
* You have problems with your adrenal glands (chronic adrenal failure).
* You take a medicine to thin your blood.
* You have a bleeding problem.
* You take certain steroid medicines.
* You cannot return for the next 2 visits.
* You cannot easily get emergency medical help in the 2 weeks after you take Mifeprex.
* You are allergic to mifepristone, misoprostol, or medicines that contain misoprostol, such as Cytotec or Arthrotec.
Tell your provider about all your medical conditions to find out if you can take Mifeprex. Also, tell your provider if you smoke at least 10 cigarettes a day.
How should I take Mifeprex?
* Day 1 at your provider's office:
- Read this Medication Guide.
- Discuss the benefits and risks of using Mifeprex to end your pregnancy.
- If you decide Mifeprex is right for you, sign the PATIENT AGREEMENT.
- After getting a physical exam, swallow 3 tablets of Mifeprex.
* Day 3 at your provider's office:
- Your provider will check to see if you are still pregnant.
* If you are still pregnant, take 2 misoprostol tablets.
* Misoprostol may cause cramps, nausea, diarrhea, and other symptoms. Your health care provider may send you home with medicines for these symptoms.
* About Day 14 at your provider's office:
- This follow-up visit is very important. You must return to the provider about 2 weeks after you took Mifeprex to be sure you are well and that you are not pregnant.
- Your provider will check whether your pregnancy has completely ended. If it has not ended, there is a chance that there may be birth defects. If you are still pregnant, your provider will talk with you about the other choices you have, including a surgical procedure to end your pregnancy.
What should I avoid while taking Mifeprex and misoprostol?
You should not take certain other medicines, because they may interfere with the treatment. Ask your provider about what medicines you can take for pain. Do not take any other prescription or non-prescription medicines (including herbal medicines or supplements) at any time during the treatment period without first asking your provider about them.
If you are breastfeeding at the time you take Mifeprex and misoprostol, discuss with your provider if you should stop using your breast milk for a few days.
What are the possible side effects of using Mifeprex?
See the section "What is the most important information I should know about Mifeprex?" for symptoms to expect.
In some cases, bleeding can be very heavy. In a very few cases, this bleeding will need to be stopped by a surgical procedure. Contact your provider right away if you bleed enough to soak through two thick full-size sanitary pads per hour for two consecutive hours or if you are concerned about heavy bleeding.
Other side effects of the treatment include diarrhea, nausea, vomiting, headache, dizziness, back pain, and tiredness. These side effects lessen after Day 3 and are usually gone by Day 14. Your provider will tell you how to manage any pain or other side effects.
If you are worried about any side effects you have, talk with your provider about them. Your provider will give you a telephone number to call if you have any questions, concerns, or problems. Your provider's telephone number is ______________________.
When should I begin birth control?
You can become pregnant again right after your pregnancy ends. If you do not want to become pregnant again, start using birth control as soon as your pregnancy ends or before you start having sexual intercourse again.
* * *
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. For more information, ask your provider for the information about Mifeprex that is written for health care professionals. Ask your provider if you have any questions.
This Medication Guide has been approved by the US Food and Drug Administration.
1. What is MIFEPREX (mifepristone) and how does it work?
Mifepristone is a drug that blocks a hormone called progesterone that is needed for pregnancy to continue. Mifepristone, when used together with another medicine called misoprostol, is used to end an early pregnancy (49 days or less since your last menstrual period began).
2. Is mifepristone approved in any other countries?
Yes, mifepristone has also been approved in the United Kingdom, Sweden and other countries.
3. Who should not take mifepristone?
Some women should not take mifepristone. Do not take mifepristone if it has been more than 49 days since your last menstrual period or if you have:
o a tubal pregnancy
o an intrauterine device (IUD) in place (It must be removed before you take mifepristone)
o problems with your adrenal glands (the glands near your kidneys)
o been treated with certain steroid medications for a long period of time
o bleeding problems or are taking anticoagulant (blood thinning) drug products
o had an allergic reaction to mifepristone, misoprostol or similar drugs
It is important that you understand the need for 2 follow-up visits with your health care provider and that you have access to a medical care facility in case of an emergency.
Mifepristone has not been studied in women who are heavy smokers. Please tell your doctor if you smoke more than 10 cigarettes a day.
4. Is mifepristone distribution restricted?
Yes, mifepristone is supplied directly to doctors who meet certain qualifications. It is not and will not be available in pharmacies, and it is not legally available over the Internet.
5. Why are there restrictions for this drug?
Studies of mifepristone were conducted by doctors who had certain qualifications. Both the drug sponsor and the 1996 Reproductive Drug Products Advisory Committee also recommended that FDA restrict distribution of mifepristone to qualified doctors. FDA has concluded that these restrictions are necessary for the safe use of the drug.
6. What qualifications must doctors have to obtain mifepristone?
Doctors must have the ability to date pregnancies accurately and to diagnose tubal pregnancies. Doctors must also be qualified to provide any necessary surgery, or have made arrangements for any necessary surgery. Doctors must ensure that women have access to medical facilities for emergency care, and must agree to other responsibilities, such as dispensing the Medication Guide and reporting any adverse events to the sponsor.
7. What authority does FDA have to restrict distribution of a drug?
The law authorizes FDA to approve new drugs only if they have been demonstrated to be safe and effective for use under the conditions of use recommended in the label. FDA has broad authority to require restrictions on distribution to ensure safe and effective use. FDA's full legal authority to restrict distribution of a drug is described in more detail in the preamble to agency drug regulations. Federal Register Notice.
8. Can health care providers other than doctors dispense mifepristone?
Some states allow physicians to supervise other health care practitioners, such as certified registered nurse practitioners and nurse midwives, and these states may allow a supervised health care provider to dispense mifepristone. Health care providers should check their state law provisions.
9. Is there an age restriction for termination of pregnancy?
State law determines whether there are any restriction on minors obtaining surgical or medical abortions. FDA has not set any separate age restriction on the provision of Mifepristone states may set age restrictions on termination of pregnancy if they believe such restrictions are appropriate..
10. Are there studies with mifepristone in women under the age of 18?
Studies to evaluate mifepristone included women ages 18-45.
11. What are the possible side effects of using mifepristone?
Mifepristone treatment will cause vaginal bleeding. In some cases vaginal bleeding can be very heavy. In a few cases, this bleeding will need to be stopped by a surgical procedure.
Other possible side effects of the treatment include diarrhea, nausea, vomiting, headache, dizziness, back pain, and tiredness.
The possible side effects are described in the Medication Guide. Please read the Medication Guide.
12. What is a Medication Guide?
A Medication Guide is a leaflet that contains certain FDA-approved information, written especially for patients.
13. Why did FDA develop a Medication Guide for mifepristone?
FDA determined that a Medication Guide was necessary for women to be able to use mifepristone effectively and safely. It is important for women to be fully informed about how mifepristone works and about its risks, as well as the need for follow-up visits with their health care provider, especially on the 14th day after mifepristone is administered. The Medication Guide will help ensure that women follow the directions for use and that they return to their health care provider for follow-up visits.
Before you receive mifepristone, your doctor will provide you with the Medication Guide and ask you to sign a statement (Patient Agreement) that you have decided to end your pregnancy.
14. Can I become pregnant again if I take mifepristone?
You can become pregnant again right after your pregnancy ends. If you do not want to get become pregnant again, start using a birth control method of your choice as soon as your pregnancy ends.
15. Does FDA endorse the use of this drug?
FDA does not endorse or promote any drug product. The agency evaluates all drug applications submitted by sponsors to determine whether a drug is safe and effective for its proposed indication under the conditions of use in the labeling. This means that the benefits of the drug outweigh its risks. The same standards were applied to the new drug application for mifepristone as are applied to all applications.
16. How much will mifepristone cost?
Manufacturers establish prices for prescription drugs. FDA has no input into or jurisdiction over drug pricing. FDA does not know what mifepristone will cost when it becomes available.
17. Will insurance companies pay for mifepristone?
The FDA has no input into or legal control over whether an insurance company does or does not cover the cost of a drug. Insurance coverage is a decision made by your insurance provider. Please call your insurance company if you have questions, about whether your particular insurance provider will cover the cost of mifepristone.
An Effective Option
Mifeprex followed by misoprostol provides a highly effective (approximately 92-95% successful), non-invasive method of ending early pregnancy. In clinical trials conducted in the United States and France, 5-8% of women who took Mifeprex, followed by misoprostol, underwent a surgical procedure identical to the procedure for miscarriage.
The Pharmacology of Mifeprex
Mifeprex blocks progesterone, a hormone necessary to maintain pregnancy. Mifeprex is taken orally followed by misoprostol, an oral prostaglandin that causes uterine contractions that help end pregnancy.
Expanded Options
In clinical studies, many women reported a greater sense of privacy with Mifeprex. Because Mifeprex is taken orally, it is an appropriate choice for patients wishing to avoid any aspect of surgery or anesthesia.
Side Effects
Bleeding and cramping are a normal part of the process. Women may experience bleeding similar to or greater than a heavy period and can expect bleeding or spotting for an average of 9-16 days. Only one out of 100 women has required surgical intervention to stop heavy bleeding. If your patient experiences severe bleeding (seen in 1% of cases), she should contact your office or an emergency number right away. Side effects that may occur include nausea, headache, vomiting, diarrhea, dizziness, fatigue and back pain. A pain reliever can be taken to alleviate discomfort.
Providing Mifeprex
Provision of Mifeprex can be easily integrated into your standard office practice. A woman makes three visits to a doctor's office or clinic over a two-week period.
At the first visit, she receives a Medication Guide (which explains how the early option works), is counseled and signs a statement that she has decided to end her pregnancy. She then takes three tablets, each containing 200 milligrams of Mifeprex.
Two days later she returns and takes two tablets each containing 200 micrograms of the prostaglandin misoprostol. A follow up visit approximately 12 days later is very important to check that the pregnancy has ended because if it has not ended, there is a chance there may be birth defects. A few women who take Mifeprex will need a surgical procedure to end the pregnancy or to stop heavy bleeding. You should communicate to your patients how you have planned to handle this possibility.
Mifeprex offers women a more private option, with support and counseling readily available throughout the process. You should give your patients a telephone number to call if they have any questions and, if different, a name and number to call in an emergency. Patients tend to call during office hours with routine questions.
More than 2,000 women participated in clinical trials in the United States. The results were published in the New England Journal of Medicine and the American Medical Association's Archives of Family Medicine Journal. In the past decade more than 1 million women worldwide have used mifepristone for ending early pregnancy. In the 3 years since FDA approval of Mifeprex in the United States, over 200,000 American women have used Mifeprex.
The American College of Obstetricians and Gynecologists (ACOG) in April 2001 published Practice Bulletin Number 26, Medical Management of Abortion, which concluded:
"Medical abortion should be considered an appropriate alternative to surgical abortion in selected, carefully counseled, and informed patients up to 49 days of gestation."