GLOBE PHARMACEUTICALS LTD.
MIFEPRISTONE + MISOPROSTOL
Mifepristone & Misoprostol tablets is indicated for medical termination of a developing intra-uterine pregnancy with a gestational age up to 49 days as measured from the first day of the Last Menstrual Period (LMP) in a presumed 28-day cycle.
Drugs acting on the Uterus, Prostaglandin analogues
Mifepristone: 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 the compound inhibits the activity of endogenous or exogenous progester-one, results the termination of pregnancy. Misoprostol: Misoprostol is a synthetic analogue of prostaglandin E1. It causes myometrial contractions by interacting with specifc receptors on myometrial cells. This interaction results in a change in calcium concentration, thereby initiating muscle contraction. By interacting with prostaglandin receptor, Misoprostol causes the cervix to soften and the uterus to contract, resulting in the expulsion of the uterine contents.
Treatment with Mifepristone & Misoprostol for the termination of pregnancy requires three times visits to the physician by the patient. Mifepristone may be administered only in a clinic, medical ofce, 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: One 200 mg tablet of Mifepristone is taken in a single oral dose. Day Two: The patient will take four 200 8g tablets (800 8g) of Misoprostol buccaly within 24-48 hours after ingesting Mifepristone at home. She should wait for 30 minutes. During the period immediately following the administration of Misoprostol, the patient may need medication for cramps or gastrointestinal symptoms. The patient should be given instructions on what to do if signifcant discomfort, excessive vaginal bleeding or other adverse reactions occur and should frequently communicate with physician. Day 14: Post-Treatment Examination Patients will return to a clinic or hospital under the supervision of the concerned physician for a follow-up visit approximately 14 days after the administration of Mifepristone. This visit is very important to confrm by clinical examination or ultrasonographic scan that a complete termination of pregnancy has occurred. 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 or as directed by the physician.
Mifepristone: Although specifc drug or food interactions with Mifepristone have not been studied, on the basis of the drug8s metabolism by CYP 3A4, it is possible that ketoconazole, itraconazole, erythromycin and grapefruit juice may inhibit its metabolism (increasing serum, levels of Mifepristone). Misoprostol: Misoprostol has not been shown to interfere with the benefcial efects of aspirin on signs & symptoms of rheumatoid arthritis. Misoprostol does not exert clinically signifcant efects on the absorption, blood levels and antiplatelet efects of therapeutic doses of aspirin.
Administration of Mifepristone & Misoprostol for the termination of pregnancy is contraindicated in patients with any one of the following conditions: Confrmed or suspected ectopic pregnancy or undiagnosed adnexal mass (the treatment procedure will not be efective to terminate an ectopic pregnancy) IUD in place Chronic adrenal failure History of allergy to Mifepristone, Misoprostol or other prostaglandin Hemorrhagic disorders or concurrent anticoagulant therapy
Mifepristone: The treatment is designed to induce the vaginal bleeding and uterine cramping necessary for menstrual Regulation (MR). Commonly reported side effects were nausea, vomiting and diarrhea, pelvic pain, fainting, headache, dizziness and asthenia occurred rarely. Misoprostol: Gastro-intestinal side effects like diarrhea, abdominal pain, nausea, flatulence, dyspepsia, headache, vomiting and constipation, shivering, hyperthermia, dizziness, pain due to uterine contractions, severe vaginal bleeding, shock, pelvic pain, uterine rupture (requiring surgical repair, hysterectomy and/or salpingo-oophorectomy).
Mifepristone & Misoprostol is indicated for use in the termination of pregnancy (through 63 days pregnancy) and has no other approved indication for use during pregnancy. 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 efects 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
Mifepristone: No serious adverse reactions were reported in tolerance studies in healthy nonpregnant female where Mifepristone is administered in single doses greater than threefold of 600 mg for menstrual regulation. If a patient ingests a massive overdose, she should be observed closely for signs of adrenal failure. Misoprostol: Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhoea, fever, palpitations, hypotension or bradycardia. Symptoms should be treated with supportive therapy. However, because Misoprostol is metabolized like a fatty acid, it is unlikely that dialysis should be appropriate treatment for overdosage.
Mifepristone & Misoprostol combination should not give to anyone else. Administration must be under the supervision of a qualified physician. The combination of Mifepristone & Misoprostol has been prescribed for the patients specific condition, it may not be the correct treatment for another patients, and may be dangerous to the other women if she is or were to become pregnant. Any intrauterine device (IUD) should be removed before treatment with Mifepristone begins. Menstrual Regulation (MR) by surgery is recommended in cases when combination of Mifepristone & Misoprostol fails to cause Menstrual Regulation. Patients who have an ongoing pregnancy at last visit have a risk of fetal malformation resulting from the treatment. Surgical termination/MVA (Manual vaccum Aspiration) is recommended to manage Menstrual Regulation (MR)/termination of pregnancy failures.
Store in a cool (below 30° C) and dry place, protected from light and moisture. Keep out of the reach of the children.