Mifeprin

Mifeprin (Mifeprin) is a cortisol receptor blocker indicated to control 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.

LIMITATIONS OF USE:

• Mifeprin should not be used in the treatment of patients with type 2 diabetes unless it is secondary to Cushing's syndrome.

Mifeprin blocks the actions of a hormone needed to maintain a pregnancy.

Mifeprin is used to end an early pregnancy (no further along than 7 weeks, or 49 days after the first day of your last menstrual period). Mifeprin is sometimes used together with another medicine called Mifeprin (Cytotec).

This medication guide provides information about the Mifeprin brand of Mifeprin. Mifeprin is another brand of Mifeprin that is not covered in this medication guide.

Mifeprin may also be used for purposes not listed in this medication guide.

Adult Dosage

The recommended starting dose is 300 mg orally once daily. Mifeprin must be given as a single daily dose. Mifeprin should always be taken with a meal. Patients should swallow the tablet whole. Do not split, crush, or chew tablets.

Dosing and titration

The daily dose of Mifeprin may be increased in 300 mg increments. The dose of Mifeprin may be increased to a maximum of 1200 mg once daily but should not exceed 20 mg/kg per day. Increases in dose should not occur more frequently than once every 2-4 weeks. Decisions about dose increases should be based on a clinical assessment of tolerability and degree of improvement in Cushing's syndrome manifestations. Changes in glucose control, antidiabetic 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 Mifeprin accompanied by monitoring for recognized adverse reactions. If treatment was interrupted because of adverse reactions, the titration should aim for a dose lower than the one that resulted in treatment interruption.

Dosing In Renal Impairment

No change in initial dose of Mifeprin is required in renal impairment. The maximum dose should be limited to 600 mg.

Dosing In Hepatic Impairment

No change in the initial dose of Mifeprin is required in mild to moderate hepatic impairment. The maximum dose should be limited to 600 mg. Mifeprin should not be used in severe hepatic impairment.

How supplied

Dosage Forms And Strengths

Mifeprin is supplied as a light yellow to yellow oval-shaped tablet debossed with “Corcept” on one side and “300” on the other. Each tablet contains 300 mg of Mifeprin. The tablets are not scored.

Storage And Handling

Mifeprin is supplied as a light yellow to yellow, film-coated, oval-shaped tablet debossed with “Corcept” on one side and “300” on the other. Each tablet contains 300 mg of Mifeprin. Mifeprin tablets are available in bottles of 28 tablets (NDC 76346-073-01) and bottles of 280 tablets (NDC 76346-073-02).

Store at controlled room temperature, 25 °C (77 °F); excursions permitted to 15 to 30 °C (59 – 86 °F).

Manufactured for: Corcept Therapeutics Incorporated, Menlo Park, CA 94025. Revised: June 2013

See also:
What is the most important information I should know about Mifeprin?

This medication guide provides information about the Mifeprin brand of Mifeprin. Mifeprin is another brand of Mifeprin that is not covered in this medication guide.

Mifeprin is used to end an early pregnancy that is not further along than 49 days (7 weeks) after the first day of your last menstrual period. Mifeprin MUST NOT BE USED IN AN ATTEMPT TO END PREGNANCY BEYOND 7 WEEKS.

Do not use Mifeprin if you do not intend to end your pregnancy. Mifeprin can cause birth defects in an unborn baby if the treatment procedure does not fully terminate the pregnancy. If you are still pregnant after 2 weeks, you may need surgery to end the pregnancy completely.

You should not take Mifeprin if you are allergic to prostaglandins or medicines that contain Mifeprin (Cytotec or Arthrotec). Do not take Mifeprin if you have a bleeding or blood clotting disorder, problems with your adrenal glands, an ectopic pregnancy, porphyria, if you take a blood thinner or certain steroid medications, or if you have an intrauterine device (IUD) in place.

Before receiving this medication, you must read a Mifeprin Medication Guide. Then you must sign a Patient Agreement form stating that you understand the risks and benefits of using this medication. Tell your doctor if you have heart disease, high blood pressure, liver or kidney disease, a breathing disorder, diabetes, anemia, or if you smoke.

Treatment with Mifeprin requires 3 visits to your doctor. Do not use this medication if you cannot attend all required follow-up visits.

Mifeprin causes cramping and bleeding, which are signs that medication is working properly. But sometimes you can have cramping and bleeding and still be pregnant. Only your doctor can confirm whether your pregnancy has been completely terminated. Do not miss any follow-up visits.

Call your doctor or seek emergency medical help if you still have any of the following symptoms more than 24 hours after taking Mifeprin: ongoing fever, severe stomach pain, heavy vaginal bleeding, nausea, vomiting, diarrhea, or if you feel like you might pass out.

It is possible to get pregnant again right after terminating a pregnancy with Mifeprin. You may begin using birth control after your doctor has confirmed that treatment with Mifeprin has effectively ended your pregnancy.

Use Mifeprin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Mifeprin comes with an extra patient information sheet called a Medication Guide and a Patient Agreement. Read them carefully. Read them again each time you get Mifeprin refilled.
• Mifeprin is supplied by your health care provider and is not available at a pharmacy.
• Mifeprin requires 3 visits to your health care provider.
• On day 1 at your health care provider's office, you will read the Medication Guide and discuss the benefits and risks of using Mifeprin to end your pregnancy. If you decide Mifeprin is right for you, sign the Patient Agreement. After your physical exam, you will take 3 tablets of Mifeprin.
• On day 3 at your health care provider's office, if you are still pregnant, you will take 2 Mifeprin tablets. Mifeprin may cause cramps, nausea, diarrhea, and other symptoms. Your health care provider may give you other medicines for these symptoms.
• Around day 14 at your health care provider's office, you will return for an important follow-up visit. You must return about 14 days after you have taken Mifeprin to be sure the pregnancy has ended. If the pregnancy has not ended, there is a chance of birth defects. Your health care provider will discuss with you your choices, including surgical abortion.
• Grapefruit and grapefruit juice may increase the risk of side effects from Mifeprin. Talk to your doctor before including grapefruit or grapefruit juice in your diet while taking Mifeprin.
• You must follow the dosing schedule as directed by your doctor. If you miss an appointment, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Mifeprin.

Use: Labeled Indications

Mifeprin: To control hyperglycemia occurring secondary to hypercortisolism in adult patients with endogenous Cushing syndrome who have type 2 diabetes mellitus or glucose intolerance and who failed surgery or who are not surgical candidates.

Limitations of use: Should not be used in the treatment of patients with type 2 diabetes unless it is secondary to Cushing syndrome.

Mifeprin: Medical termination of intrauterine pregnancy through 70 days gestation, in combination with Mifeprin.

Off Label Uses

Early pregnancy loss

Data from a randomized study support the use of Mifeprin in conjunction with Mifeprin for the management of early pregnancy loss (<13 weeks gestation).

See also:
What other drugs will affect Mifeprin?

Based on the long terminal half-life of Mifeprin after reaching steady state, at least 2 weeks should elapse after cessation of Mifeprin before initiating or increasing the dose of any interacting concomitant medication.

Drugs Metabolized By CYP3A

Because Mifeprin is an inhibitor of CYP3A, concurrent use of Mifeprin with a drug whose metabolism is largely or solely mediated by CYP3A is likely to result in increased plasma concentrations of the drug. Discontinuation or dose reduction of such medications may be necessary with Mifeprin co-administration.

Mifeprin increased the exposure to simvastatin and simvastatin acid significantly in healthy subjects. Concomitant use of simvastatin or lovastatin is contraindicated because of the increased risk of myopathy and rhabdomyolysis. The exposure of other substrates of CYP3A with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus, may be increased by concomitant administration with Mifeprin. Therefore, the concomitant use of such CYP3A substrates with Mifeprin is contraindicated.

Other drugs with similar high first pass metabolism in which CYP3A is the primary route of metabolism should be used with extreme caution if co-administered with Mifeprin. The lowest possible dose and/or a decreased frequency of dosing must be used with therapeutic drug monitoring when possible. Use of alternative drugs without these metabolic characteristics is advised when possible with concomitant Mifeprin.

If drugs that undergo low first pass metabolism by CYP3A or drugs in which CYP3A is not the major metabolic route are co-administered with Mifeprin, use the lowest dose of concomitant medication necessary, with appropriate monitoring and follow-up.

CYP3A Inhibitors

Medications that inhibit CYP3A could increase plasma Mifeprin concentrations and dose reduction of Mifeprin may be required.

Ketoconazole and other strong inhibitors of CYP3A, such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir and fosamprenavir, boceprevir, clarithromycin, conivaptan, lopinavir, mibefradil, posaconazole, saquinavir, telaprevir, telithromycin, or voriconazole may increase exposure to Mifeprin significantly. The clinical impact of this interaction has not been studied. Therefore, extreme caution should be used when these drugs are prescribed in combination with Mifeprin.

The benefit of concomitant use of these agents should be carefully weighed against the potential risks. The dose of Mifeprin should be limited to 300 mg and used only when necessary.

Moderate inhibitors of CYP3A, such as amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, or verapamil, should be used with caution when administered in combination with Mifeprin.

CYP3A Inducers

No medications that induce CYP3A have been studied when co-administered with Mifeprin. Avoid co-administration of Mifeprin and CYP3A inducers such as rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John's wort.

Drugs Metabolized By CYP2C8/2C9

Because Mifeprin is an inhibitor of CYP2C8/2C9, concurrent use of Mifeprin with a drug whose metabolism is largely or solely mediated by CYP2C8/2C9 is likely to result in increased plasma concentrations of the drug.

Mifeprin significantly increased exposure of fluvastatin, a typical CYP2C8/2C9 substrate, in healthy subjects. When given concomitantly with Mifeprin, drugs that are substrates of CYP2C8/2C9 (including non-steroidal anti-inflammatory drugs, warfarin, and repaglinide) should be used at the smallest recommended doses, and patients should be closely monitored for adverse effects.

Drugs Metabolized By CYP2B6

Mifeprin is an inhibitor of CYP2B6 and may cause significant increases in exposure of drugs that are metabolized by CYP2B6 such as bupropion and efavirenz. Since no study has been conducted to evaluate the effect of Mifeprin on substrates of CYP2B6, the concomitant use of bupropion and efavirenz should be undertaken with caution.

Use Of Hormonal Contraceptives

Mifeprin is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used.

See also:
What are the possible side effects of Mifeprin?

Applies to Mifeprin: oral tablet

In addition to its needed effects, some unwanted effects may be caused by Mifeprin (the active ingredient contained in Mifeprin). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking Mifeprin:

Less common:

• Excessively heavy vaginal bleeding
• unusual tiredness or weakness

• Chest pain or discomfort
• confusion
• cough or hoarseness
• fast, weak pulse
• fever or chills
• lower back or side pain
• pain or discomfort in the arms, jaw, back, or neck
• painful or difficult urination
• pale, cold, or clammy skin
• shortness of breath
• sudden increase in stomach or shoulder pain
• sweating
• unusual or large amount of vaginal bleeding

Minor Side Effects

Some of the side effects that can occur with Mifeprin may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

• Abdominal or stomach pain or uterine cramping
• back pain
• diarrhea
• dizziness
• headache
• nausea or vomiting

• Acid or sour stomach
• anxiety
• belching
• cough
• fainting or lightheadedness 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 the eyes and cheekbones
• pale skin
• shaking chills
• shortness of breath or troubled breathing
• sleeplessness or trouble sleeping
• stomach discomfort, upset, or pain
• stuffy or runny nose
• tightness of the chest or wheezing
• troubled breathing, exertional
• unusual bleeding or bruising

A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome [PubChem]. The two marketed forms of Mifeprin are Mifeprin® (Mifeprin 200mg) and Mifeprin™ (Mifeprin 300mg). Currently under investigation for use in psychotic depression (phase 3 trials).