A Kare

Mifepristone (A Kare) (Mifepristone (A Kare)) 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:

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

Misoprostol (A Kare) (Misoprostol (A Kare)) is indicated for reducing the risk of NSAID (nonsteroidal anti-inflammatory drugs, including aspirin)–induced gastric ulcers in patients at high risk of complications from gastric ulcer, e.g., the elderly and patients with concomitant debilitating disease, as well as patients at high risk of developing gastric ulceration, such as patients with a history of ulcer. Misoprostol (A Kare) has not been shown to reduce the risk of duodenal ulcers in patients taking NSAIDs. Misoprostol (A Kare) should be taken for the duration of NSAID therapy. Misoprostol (A Kare) has been shown to reduce the risk of gastric ulcers in controlled studies of 3 months' duration. It had no effect, compared to placebo, on gastrointestinal pain or discomfort associated with NSAID use.

Mifepristone (A Kare) blocks the actions of a hormone needed to maintain a pregnancy.

Mifepristone (A Kare) 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). Mifepristone (A Kare) is sometimes used together with another medicine called misoprostol (Cytotec).

This medication guide provides information about the Mifepristone (A Kare) brand of Mifepristone (A Kare). Mifepristone (A Kare) is another brand of Mifepristone (A Kare) that is not covered in this medication guide.

Mifepristone (A Kare) may also be used for purposes not listed in this medication guide.

Misoprostol (A Kare) is taken to prevent stomach ulcers in patients taking anti-inflammatory drugs, including aspirin. Misoprostol (A Kare) may also be used for other conditions as determined by your doctor.

Misoprostol (A Kare) helps the stomach protect itself against acid damage. It also decreases the amount of acid produced by the stomach.

Misoprostol (A Kare) is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Misoprostol (A Kare) may be used in certain patients with the following medical conditions:

• Abortion, first trimester
• Abortion, second trimester
• Cervical ripening
• Induction of labor
• Postpartum hemorrhage

Adult Dosage

The recommended starting dose is 300 mg orally once daily. Mifepristone (A Kare) must be given as a single daily dose. Mifepristone (A Kare) 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 Mifepristone (A Kare) may be increased in 300 mg increments. The dose of Mifepristone (A Kare) 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 Mifepristone (A Kare) 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 Mifepristone (A Kare) 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 Mifepristone (A Kare) is required in mild to moderate hepatic impairment. The maximum dose should be limited to 600 mg. Mifepristone (A Kare) should not be used in severe hepatic impairment.

How supplied

Dosage Forms And Strengths

Mifepristone (A Kare) 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 Mifepristone (A Kare). The tablets are not scored.

Storage And Handling

Mifepristone (A Kare) 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 Mifepristone (A Kare). Mifepristone (A Kare) 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

Usual Adult Dose for Duodenal Ulcer

200 mcg orally 4 times a day after meals and at bedtime.

For duodenal ulcers: Alternatively, 400 mcg orally 2 times a day may be used.

Usual Adult Dose for Gastric Ulcer

200 mcg orally 4 times a day after meals and at bedtime.

For duodenal ulcers: Alternatively, 400 mcg orally 2 times a day may be used.

Usual Adult Dose for NSAID-Induced Ulcer Prophylaxis

200 mcg orally 4 times a day after meals and at bedtime.

For duodenal ulcers: Alternatively, 400 mcg orally 2 times a day may be used.

Usual Adult Dose for Labor Induction

25 mcg vaginally every 4 to 6 hours.

Usual Adult Dose for Postpartum Bleeding

Prophylaxis: 400 to 600 mcg orally or rectally after delivery of the baby, but before delivery of the placenta.

Usual Adult Dose for Cervical Ripening

Before surgical abortion: 400 mcg vaginally, 3 to 4 hours before suction curettage.

Usual Adult Dose for Abortion

First Trimester of Pregnancy: 400 mcg orally once as a single dose 48 hours after Misoprostol (A Kare) administration. Alternatively, 800 mcg vaginally 48 hours after Misoprostol (A Kare) administration. When used with methotrexate, 5 to 7 days later give 800 mcg vaginally (Misoprostol (A Kare) dose may be repeated 24 hours later if needed).

In Failed Pregnancy or Fetal Death: 800 mcg vaginally once or twice (doses given 24 hours apart).

Second Trimester of Pregnancy: 600 mcg vaginally, 36 to 48 hours after Misoprostol (A Kare) administration, followed by 400 mcg orally or vaginally every 3 hours to a maximum of 5 doses in the first 24 hours.

Third Trimester of Pregnancy - Fetal Death: 100 mcg vaginally every 12 hours.

Usual Adult Dose for Gynecologic Surgery

Study (n=204) - Operative hysteroscopy: 400 mcg orally 12 to 24 hours before surgery.

Usual Pediatric Dose for NSAID-Induced Ulcer Prophylaxis

Study (n=25)

>7 years: 9.8 mcg/kg/day, given in two equally divided doses daily, to a maximum of 800 mcg/day.

Renal Dose Adjustments

No dose adjustment is routinely needed, but dosage can be reduced if the 200 mcg dose is not tolerated.

Liver Dose Adjustments

Data not available

Dose Adjustments

The dose may be reduced to 100 mcg orally 4 times a day or 200 mcg orally 2 times a day if the patient is unable to tolerate the recommended regimen or if the patient is maintained on chronic hemodialysis.

50 mcg every 6 hours may be appropriate for cervical ripening or labor induction in the third trimester in some situations, although higher doses appear to be associated with uterine tachysystole and possibly with uterine hyperstimulation and meconium staining of amniotic fluid.

Misoprostol (A Kare) should not be administered more frequently than every 3 to 6 hours.

Precautions

Consult WARNINGS section for dosing related precautions.

Dialysis

In patients maintained on prolonged hemodialysis, start patient at the lower dose.

It is not known if Misoprostol (A Kare) is dialyzable. However, because Misoprostol (A Kare) is metabolized like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage.

Other Comments

Misoprostol (A Kare) is not considered a first-line agent for the treatment of duodenal ulcers, or gastric ulcers. There is no evidence that Misoprostol (A Kare) is more efficacious than H2-antagonists in these settings.

Misoprostol (A Kare) can cause miscarriage, often associated with potentially dangerous bleeding. This may result in hospitalization, surgery, infertility or death. Do not take Misoprostol (A Kare) if pregnant and do not become pregnant while on this medication. If pregnancy occurs during Misoprostol (A Kare) therapy, discontinue the drug and contact physician immediately.

ADDITIONAL CONSIDERATIONS: Patients should not give medication to anyone else. Patient should read the leaflet included with medication each time the prescription is renewed.

See also:
What is the most important information I should know about Mifepristone (A Kare)?

This medication guide provides information about the Mifepristone (A Kare) brand of Mifepristone (A Kare). Mifepristone (A Kare) is another brand of Mifepristone (A Kare) that is not covered in this medication guide.

Mifepristone (A Kare) 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. Mifepristone (A Kare) MUST NOT BE USED IN AN ATTEMPT TO END PREGNANCY BEYOND 7 WEEKS.

Do not use Mifepristone (A Kare) if you do not intend to end your pregnancy. Mifepristone (A Kare) 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 Mifepristone (A Kare) if you are allergic to prostaglandins or medicines that contain misoprostol (Cytotec or Arthrotec). Do not take Mifepristone (A Kare) 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 Mifepristone (A Kare) 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 Mifepristone (A Kare) requires 3 visits to your doctor. Do not use this medication if you cannot attend all required follow-up visits.

Mifepristone (A Kare) 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 Mifepristone (A Kare): 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 Mifepristone (A Kare). You may begin using birth control after your doctor has confirmed that treatment with Mifepristone (A Kare) has effectively ended your pregnancy.

See also:
What is the most important information I should know about Misoprostol (A Kare)?

Hypersensitivity to Misoprostol (A Kare) or to any components of Misoprostol (A Kare) or to other prostaglandins.

Use in pregnancy: Misoprostol (A Kare) is contraindicated in pregnant women or in whom pregnancy has not been excluded, or who are planning a pregnancy as Misoprostol (A Kare) increases uterine tone and contractions in pregnancy which may cause partial or complete expulsion of the products of conception. Use in pregnancy has been associated with birth defects.

Misoprostol (A Kare) is contraindicated in women who are pregnant because it induces uterine contractions and is associated with abortion, premature birth, foetal death and birth defects. First trimester exposure to Misoprostol (A Kare) is associated with a significantly increased risk of 2 birth defects: Mobius sequence (ie, palsies of cranial nerves VI and VII), and terminal transverse limb defects. Other defects including arthrogryposis have been observed.

The risk of uterine rupture increases with advancing gestational age and with prior uterine surgery, including Caesarean delivery. Grand multiparity also appears to be a risk factor for uterine rupture.

Women of childbearing potential should not be started on Misoprostol (A Kare) until pregnancy is excluded and should be fully counseled on the importance of adequate contraception while undergoing treatment. If pregnancy is suspected, use of the product should be discontinued.

In such patients, it is advised that Misoprostol (A Kare) should only be used if the patient takes effective contraceptive measures or has been advised of the risks of taking Misoprostol (A Kare) if pregnant.

Use in lactation: Misoprostol (A Kare) is rapidly metabolised in the mother to Misoprostol (A Kare) acid, which is biologically active and is excreted in breast milk. Misoprostol (A Kare) should not be administered to nursing mothers because the excretion of Misoprostol (A Kare) acid could cause adverse reactions eg, diarrhoea in nursing infants.

Use Mifepristone (A Kare) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Mifepristone (A Kare) 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 Mifepristone (A Kare) refilled.
• Mifepristone (A Kare) is supplied by your health care provider and is not available at a pharmacy.
• Mifepristone (A Kare) 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 Mifepristone (A Kare) to end your pregnancy. If you decide Mifepristone (A Kare) is right for you, sign the Patient Agreement. After your physical exam, you will take 3 tablets of Mifepristone (A Kare).
• On day 3 at your health care provider's office, if you are still pregnant, you will take 2 misoprostol tablets. Misoprostol 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 Mifepristone (A Kare) 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 Mifepristone (A Kare). Talk to your doctor before including grapefruit or grapefruit juice in your diet while taking Mifepristone (A Kare).
• 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 Mifepristone (A Kare).

Use Misoprostol (A Kare) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Misoprostol (A Kare). Talk to your pharmacist if you have questions about this information.
• Take Misoprostol (A Kare) by mouth with food unless your doctor tells you otherwise.
• The last dose of the day should be taken at bedtime. Taking Misoprostol (A Kare) after meals and at bedtime may decrease the risk of diarrhea.
• Do not take an antacid that has magnesium in it within 1 hour before or 2 hours after you take Misoprostol (A Kare).
• If you miss a dose of Misoprostol (A Kare), take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Misoprostol (A Kare).

Use: Labeled Indications

Mifepristone (A Kare): 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.

Mifepristone (A Kare): Medical termination of intrauterine pregnancy through 70 days gestation, in combination with misoprostol.

Off Label Uses

Early pregnancy loss

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

Use: Labeled Indications

NSAID-induced gastric ulcers, prevention: To reduce the risk of NSAID-induced gastric ulcers in patients at high risk of complications

Termination of intrauterine pregnancy: Medical termination of intrauterine pregnancy through 70 days' gestation in combination with Misoprostol (A Kare) (Misoprostol (A Kare) prescribing information March 2016)

Off Label Uses

Cervical ripening and labor induction

Based on the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin: Induction of Labor, Misoprostol (A Kare) tablets administered intravaginally for cervical ripening and labor induction is effective and recommended in the management of this condition.

See also:
What other drugs will affect Mifepristone (A Kare)?

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

Drugs Metabolized By CYP3A

Because Mifepristone (A Kare) is an inhibitor of CYP3A, concurrent use of Mifepristone (A Kare) 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 Mifepristone (A Kare) co-administration.

Mifepristone (A Kare) 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 Mifepristone (A Kare). Therefore, the concomitant use of such CYP3A substrates with Mifepristone (A Kare) 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 Mifepristone (A Kare). 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 Mifepristone (A Kare).

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 Mifepristone (A Kare), use the lowest dose of concomitant medication necessary, with appropriate monitoring and follow-up.

CYP3A Inhibitors

Medications that inhibit CYP3A could increase plasma Mifepristone (A Kare) concentrations and dose reduction of Mifepristone (A Kare) 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 Mifepristone (A Kare) 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 Mifepristone (A Kare).

The benefit of concomitant use of these agents should be carefully weighed against the potential risks. The dose of Mifepristone (A Kare) 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 Mifepristone (A Kare).

CYP3A Inducers

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

Drugs Metabolized By CYP2C8/2C9

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

Mifepristone (A Kare) significantly increased exposure of fluvastatin, a typical CYP2C8/2C9 substrate, in healthy subjects. When given concomitantly with Mifepristone (A Kare), 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

Mifepristone (A Kare) 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 Mifepristone (A Kare) on substrates of CYP2B6, the concomitant use of bupropion and efavirenz should be undertaken with caution.

Use Of Hormonal Contraceptives

Mifepristone (A Kare) 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 other drugs will affect Misoprostol (A Kare)?

Antacids: May enhance the adverse/toxic effect of Misoprostol (A Kare). More specifically, concomitant use with magnesium-containing antacids may increase the risk of diarrhea. Management: Avoid concomitant use of Misoprostol (A Kare) and magnesium-containing antacids. In patients requiring antacid therapy, employ magnesium-free preparations. Monitor for increased adverse effects (e.g., diarrhea, dehydration). Exceptions: Aluminum Hydroxide; Calcium Carbonate; Potassium Bicarbonate; Sodium Bicarbonate. Avoid combination

Carbetocin: Misoprostol (A Kare) may enhance the adverse/toxic effect of Carbetocin. Specifically, Carbetocin oxytocic effects may be enhanced. Avoid combination

Oxytocin: Misoprostol (A Kare) may enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: The manufacturer of Misoprostol (A Kare) recommends avoiding concomitant use with oxytocin. Misoprostol (A Kare) may augment effects of oxytocin, particularly when given within 4 hours of oxytocin initiation. Consider therapy modification

Phenylbutazone: May enhance the neurotoxic effect of Misoprostol (A Kare). Specifically, the combination may result in headache, dizziness, and transient diplopia. Monitor therapy

See also:
What are the possible side effects of Mifepristone (A Kare)?

Applies to Mifepristone (A Kare): oral tablet

In addition to its needed effects, some unwanted effects may be caused by Mifepristone (A Kare) (the active ingredient contained in Mifepristone (A Kare)). 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 Mifepristone (A Kare):

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 Mifepristone (A Kare) 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

See also:
What are the possible side effects of Misoprostol (A Kare)?

The following have been reported as adverse events in subjects receiving Misoprostol (A Kare):

Gastrointestinal

In subjects receiving Misoprostol (A Kare) 400 or 800 mcg daily in clinical trials, the most frequent gastrointestinal adverse events were diarrhea and abdominal pain. The incidence of diarrhea at 800 mcg in controlled trials in patients on NSAIDs ranged from 14–40% and in all studies (over 5,000 patients) averaged 13%. Abdominal pain occurred in 13–20% of patients in NSAID trials and about 7% in all studies, but there was no consistent difference from placebo.

Diarrhea was dose related and usually developed early in the course of therapy (after 13 days), usually was self-limiting (often resolving after 8 days), but sometimes required discontinuation of Misoprostol (A Kare) (2% of the patients). Rare instances of profound diarrhea leading to severe dehydration have been reported. Patients with an underlying condition such as inflammatory bowel disease, or those in whom dehydration, were it to occur, would be dangerous, should be monitored carefully if Misoprostol (A Kare) is prescribed. The incidence of diarrhea can be minimized by administering after meals and at bedtime, and by avoiding coadministration of Misoprostol (A Kare) with magnesium-containing antacids.

Gynecological

Women who received Misoprostol (A Kare) during clinical trials reported the following gynecological disorders: spotting (0.7%), cramps (0.6%), hypermenorrhea (0.5%), menstrual disorder (0.3%) and dysmenorrhea (0.1%). Postmenopausal vaginal bleeding may be related to Misoprostol (A Kare) administration. If it occurs, diagnostic workup should be undertaken to rule out gynecological pathology.

Elderly

There were no significant differences in the safety profile of Misoprostol (A Kare) in approximately 500 ulcer patients who were 65 years of age or older compared with younger patients.

Additional adverse events which were reported are categorized as follows:

Incidence greater than 1%

In clinical trials, the following adverse reactions were reported by more than 1% of the subjects receiving Misoprostol (A Kare) and may be causally related to the drug: nausea (3.2%), flatulence (2.9%), headache (2.4%), dyspepsia (2.0%), vomiting (1.3%), and constipation (1.1%). However, there were no significant differences between the incidences of these events for Misoprostol (A Kare) and placebo.

Causal relationship unknown

The following adverse events were infrequently reported. Causal relationships between Misoprostol (A Kare) and these events have not been established but cannot be excluded:

Body as a whole: aches/pains, asthenia, fatigue, fever, chills, rigors, weight changes.

Skin: rash, dermatitis, alopecia, pallor, breast pain.

Special senses: abnormal taste, abnormal vision, conjunctivitis, deafness, tinnitus, earache.

Respiratory: upper respiratory tract infection, bronchitis, bronchospasm, dyspnea, pneumonia, epistaxis.

Cardiovascular: chest pain, edema, diaphoresis, hypotension, hypertension, arrhythmia, phlebitis, increased cardiac enzymes, syncope, myocardial infarction (some fatal), thromboembolic events (e.g., pulmonary embolism, arterial thrombosis, and CVA).

Gastrointestinal: GI bleeding, GI inflammation/infection, rectal disorder, abnormal hepatobiliary function, gingivitis, reflux, dysphagia, amylase increase.

Hypersensitivity: anaphylactic reaction

Metabolic: glycosuria, gout, increased nitrogen, increased alkaline phosphatase.

Genitourinary: polyuria, dysuria, hematuria, urinary tract infection.

Nervous system/Psychiatric: anxiety, change in appetite, depression, drowsiness, dizziness, thirst, impotence, loss of libido, sweating increase, neuropathy, neurosis, confusion.

Musculoskeletal: arthralgia, myalgia, muscle cramps, stiffness, back pain.

Blood/Coagulation: anemia, abnormal differential, thrombocytopenia, purpura, ESR increased.

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 Mifepristone (A Kare) are Mifepristone (A Kare)® (Mifepristone (A Kare) 200mg) and Mifepristone (A Kare)™ (Mifepristone (A Kare) 300mg). Currently under investigation for use in psychotic depression (phase 3 trials).

Each tablet contains Misoprostol (A Kare) 200 mcg. Misoprostol (A Kare) also contains the following excipients: Microcrystalline cellulose, sodium starch glycolate (type A), hydogenated castor oil and hypromellose.