Mifebax Kit

Uses

Mifepristone & Misoprostol tablets is used 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.

Mifebax Kit is also used to associated treatment for these conditions: Hyperglycemia, Pregnancy TerminationGastric Ulcer, Incomplete Abortion, Missed Abortion, Postpartum Haemorrhage (PPH), Induction of cervix ripening therapy, Medically induced abortion

How Mifebax Kit works

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 (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results.

In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.

Misoprostol is a synthetic prostaglandin E1 analog that stimulates prostaglandin E1 receptors on parietal cells in the stomach to reduce gastric acid secretion. Mucus and bicarbonate secretion are also increased along with thickening of the mucosal bilayer so the mucosa can generate new cells.

Misoprostol binds to smooth muscle cells in the uterine lining to increase the strength and frequency of contractions as well as degrade collagen and reduce cervical tone.

Dosage

Mifebax Kit dosage

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 embryoand 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 µg tablets (800 µg) 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.

There are no precautions for timing in relation to food.

Side Effects

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).

Toxicity

Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy menstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea.

The oral LD₅₀ in rats is 81mg/kg and in mice is 27mg/kg. The intraperitoneal LD₅₀ in rats is 40mg/kg and in mice is 70mg/kg.

Patients experiencing an overdose may present with sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhea, fever, palpitations, hypotension, and bradycardia. Hemodialysis is not expected to be useful in the treatment of misoprostol overdose but oral activated charcoal may help reduce absorption. In the event of an overdose, treat symptoms with supportive therapy. This may include removal of undissolved tablets from the vagina or buccal cavity, intravenous fluid replacement, acetaminophen, diazepam, haloperidol, or intramuscular diclofenac depending on the symptoms that present.

Precaution

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.

Interaction

Mifepristone: Although specifc drug or food interactions with Mifepristone have not been studied, on the basis of the drug’s 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.

Volume of Distribution

Data regarding the volume of distribution of misoprostol is scarce.

The apparent volume of distribution of the active metabolite of misoprostol was in subjects with normal renal function was 13.6±8.0L/kg, with mild renal impairment was 17.3±23.0L/kg, with moderate renal impairment was 14.3±6.8L/kg, and with end stage renal disease was 11.0±9.6L/kg.

Elimination Route

The absolute bioavailability of a 20 mg oral dose is 69%

For an 800µg oral dose of misoprostol, the AUC was 2.0192±0.8032h*ng/mL, the C_max was 2.6830±1.2161ng/mL, and a t_max of 0.345±0.186h. For a 800µg sublingual dose of misoprostol, the AUC was 3.2094±1.0417h*ng/mL, the C_max was 2.4391±1.1567ng/mL, and a t_max of 0.712±0.415h. For a 800µg buccal dose of misoprostol, the AUC was 2.0726±0.3578h*ng/mL, the C_max was 1.3611±0.3436ng/mL, and a t_max of 1.308±0.624h.

Half Life

18 hours

The half life of an 800µg oral dose is 1.0401±0.5090h, for a sublingual dose is 0.8542±0.1170h, and for a buccal dose is 0.8365±0.1346h.

Clearance

Because of the rapid de-esterification of misoprostol before or during absorption, it is usually undetectable in plasma. Misoprostol's active metabolite, misoprostol acid, has a total body clearance of 0.286L/kg/min. Subjects with mild renal impairment had a total body clearance of 0.226±0.073L/kg/min, subjects with moderate renal impairment had a total body clearance of 0.270±0.103L/kg/min, and subjects with end stage renal disease had a total body clearance of 0.105±0.052L/kg/min.

Elimination Route

Fecal: 83%; Renal: 9%.

As much as 73.2±4.6% of a radiolabelled oral dose of misoprostol is recovered in the urine.

Pregnancy & Breastfeeding use

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

Contraindication

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

Special Warning

Geriatrics: This is not indicated in post-menopausal women.

Pediatrics (less than 18 years of age): There are insufficient data in patients less than 15 years old to establish efficacy and safety.

Acute Overdose

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.

Storage Condition

Store in a cool (below 30° C) and dry place, protected from light and moisture. Keep out of the reach of the children.

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