Femiclean Kit: Combipack Of Mifepristone & Misoprostol Tablets

Contents

Femiclean kit contains 1 tablet of mifepristone 200mg to be given orally and 4 tablets of 200mcg misoprostol to be given vaginally for the medical termination of pregnancy up to 9 weeks. This kit has been developed in accordance with guidelines issued by the Royal College of Obstetricians and Gynecologists UK.

Mifepristone has anti-progestational activity. As Mifepristone inhibits the activity of progesterone it results in termination of pregnancy. Mifepristone also exhibits antiglucocorticoid and weak anti-androgenic activity.

Misoprostol is a synthetic prostsglandin E1. Misoprostol causes the cervix to soften and the uterus to contract and also inhibits gastric acid secretion in humans.

Pharmacology

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

Doses of 1mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contradiction-inducing activity of prostaglandins.

Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. Doses of 4.5mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTC) and cortisol. Antiandrogenic activity was observed in rats following repeated administration of doses from 10 to 100 mg/kg

Misoprostol

Prostaglandin E1 causes myometrial contraction by interacting with specific receptor on myometrial cells, this interaction results in a change in calcium concentration thereby initiating contraction. By interacting with prostaglandin receptors, misoprostol causes the cervix to soften and the uterus to contract, resulting in the expulsion of the uterine contents.

Indications

Femiclean kit is indicated for early medical abortion up to 9 weeks (63 days) of gestation.

Dosage and administration

Femiclean Kit is indicated for the medical termination of intrauterine pregnancy up to 63 days of gestation. For purpose of this treatment pregnancy is dated from the first day of the last menstrual period in a presumed 28 days cycle with ovulation occurring at mid cycle.

The duration of pregnancy may be determined from menstrual history and by clinical examination. Ultrasonographic scan should be used if the duration of pregnancy is uncertain, or if ectopic pregnancy is suspected.

Any intrauterine device “IUD” should be removed before treatment with mifepristone and misoprostol begins. Pregnancy termination by surgery is recommended in cases when Femiclean Kit fails to cause termination of intrauterine pregnancy.

Mifepristone may be administered by or under supervision of a gynecologist able to asses the gestation age of an embryo and to diagnose ectopic pregnancies. The gynecologist 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 the patient access to medical facilities and resuscitation, if necessary.

The dosage is mifepristone 200mg orally followed 1-3 days later by misoprostol 800mcg (4 tablets of 200mcg each) vaginally. The misoprostol may be administered by a clinician or self-administered by the woman. For women at 49-63 days of gestation, if abortion has not occurred 4 hours after administration of misoprostol, a second dose of misoprostol 400mcg (2 tablets) may be administered vaginally or orally depending upon preference and amount of bleeding.

The patient should return for a follow-up visit approximately 14 days after the administration of mifepristone. This visit is very important to confirm by clinician examination of ultrasonographic scan that a complete termination of pregnancy has occurred. Patients who have an ongoing pregnancy at this visit have a risk of foetal malformation resulting from the treatment. Surgical termination is recommended to manage medical abortion treatment failures.

Contraindications

Administration of mifepristone and misoprostol for the termination of pregnancy is contraindicated to patients with any of the following conditions:

History of allergy of known hypersensitivity to mifepristone, misoprostol or other prostaglandin.
Confirmed of suspected ectopic pregnancy of undiagnosed adnexal mass (the treatment procedure will not be effective to terminate an ectopic pregnancy)
IUD in place
Chronic adrenal failure
Haemorrhagic disorders or concurrent anticoagulant therapy
Inherited porphyria
If a patient does not have adequate access to medical facilities equipped to provide emergency treatment of incomplete abortion, blood transfusions, and emergency resuscitation during the period from the first visit until discharged by the administering physician.

Warnings and precautions

The patient should not give Femiclean Kit to anyone else. The Femiclean Kit has been prescribed for the patient’s specific condition. It may not be the correct treatment for another person and may be dangerous to the other person if she is or were to become pregnant.

Any intrauterine device, “IUD” should be removed before treatment with mifepristone begins. Pregnancy termination by surgery is recommended in case when Femiclean Kit fails to cause termination of intrauterine pregnancy. Patients who have an ongoing pregnancy at last visit have a risk of foetal malformation resulting from the treatment. Surgical termination is recommended to manage medical abortion treatment failures.

Mifepristone

There are no data on safety and efficacy of mifepristone in women with chronic medical conditions such as cardiovascular, hypertensive, hepatic, respiratory or renal disease; insulin-dependent diabetes mellitus, severe anaemia or heavy smoking. Women who are more than 35 years of age and who also smoke 10 or more cigarettes per day should be treated with caution because such patients were generally excluded from clinical trials of mifepristone. Although there is no clinical evidence, the effectiveness of mifepristone may be lower if misoprostol is administered more than two days after mifepristone administration.

Bleeding

Vaginal bleeding occurs in almost all patients during the treatment procedure. In general the duration of bleeding and spotting increased as the duration of the pregnancy increased. Normally it lasts for an average of 9 to 16 days. In some cases excessive bleeding may require treatment by vasoconstrictor drugs, curettage, and administration of saline infusions and/or blood transfusions. Prolonged bleeding heavy bleeding may be a sign of incomplete abortion of other complications and require prompt and immediate medical attention.

Confirmation of pregnancy termination

Patients should be scheduled for and return for a follow-up visit at approximately 14 daysafter administration of mifepristone to confirm that the pregnancy is completely terminated and to assess the degree of bleeding. Vaginal bleeding is not evidence of termination of pregnanacy. Termination can be confirmed by clinical examination of ultrasonographic scan. Lack of bleeding following treatment, however, usually indicates failure, medical abortion failures should be managed with surgical termination.

Infections and sepsis

Cases of serious bacterial infections including very rare cases of fatal septic shock have been reported. no casual relationship between these events and use of mifepristone and misoprostol has been established. A sustained fever of 100.4 degree or higher, severe abdominal pain, pr pelvic tenderness in the days after medical abortion may indicate infection and sepsis without these symptoms but with significant leucocytosis, tachycardia or haemo concentration can occur.

Ectopic pregnancy

Mifepristone is contraindicated in confirmed or suspected ectopic pregnancy since it is not effective for terminating these pregnancies. There could be a possibility that a patient who is undergoing a medical abortion could have an undiagnosed ectopic pregnancy since some of the expected symptoms of a medical abortion may be similar to those of a ruptured ectopic pregnancy. The presence of an ectopic pregnancy may have been missed even if the patient underwent ultrasonography prior to being prescribed Femiclean Kit.

Drug interactions

Mifepristone

Although specific drug or blood interactions with mifepristone have not been studied, on the basis of this drug’s metabolism by CYP 3A4, it is possible that ketoconazole, itraconazole, erythromycin and grape fruit juice may inhibit its metabolism (increasing serum levels of Mifepristone). Furthermore, rifampin, dexamethasone, St. john’s Wort, and certain anticonvulsants (phenytoin, phenobarbital, carbamazepine) may induce mifepristone metabolism (lowering serum levels of mifepristone)

Based on in vitro inhibition information, administration of mifepristone may lead to an increase in serum levels of drugs that are CYP 3A4 substrate. Due to the slow elimination of mifepristone from the body, such interaction may be observed for a prolonged period after its administration. Therefore caution should be exercised when mifepristone is administered with drugs that are CYP3A4 substrates and have narrow therapeutic range, including some agents used during general anesthesia.

Misoprostol

Misoprostol has not been shown to interfere with the beneficial effects of aspirin on signs and symptoms of rheumatoid arthritis.

Misoprostol does not exert clinically significant effect on the absorption, blood levels and antiplatelet effects of therapeutic dose of aspirin.

Misoprostol has no clinically significant effect on the kinetics of diclofenac or ibuprofen.

The most common side effects of misoprostol are diarrhea and abdominal pain , these side effects may be increased if misoprostol is taken concurrently with antacids.

Renal impairment

Misoprostol: Pharmacokinetic studies in patients with varying degrees of renal impairment showed and approximate doubling of T _½ C_max and AUC compared to normal, but no clear correlation between the degree of impairment and AUC.

In subjects over 64 years of age, the AUC for misoprostol acid is increased. No routine dosage adjustment is recommended in other patients or patients with renal impairment, but dosage may need to be reduced if the usual dose is not tolerated.

Hepatic impairment

Misoprostol: Patients with hepatic disease should receive a decreased dose.

Pregnancy:

Mifepristone is indicated for use in the termination of pregnancy (through 63 days pregnancy) and has no other approved indication for use during pregnancy. Patients who have an ongoing pregnancy at the last visit have a risk of foetal malformation resulting from the treatment. Surgical termination is recommended to manage medical abortion treatment failures.

Undesirable effects

Mifepristone

The treatment procedure is designed to induce the vaginal bleeding and uterine cramping necessary to produce an abortion. Nearly all the women who receive mifepristone and misoprostol 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 treatment procedure. Women typically experienced abdominal pain, including uterine cramping. Other commonly reported side effects were nausea, vomiting and diarrhea, pelvic pain, fainting, headache, dizziness and asthenia occurred rarely.

Misoprostol

Gastrointestinal side effects like diarrhea, abdominal pain, nausea, flatulence, dyspepsia, headache, vomiting and constipation
Shivering
Hyperthermia
Dizziness
Pain due to uterine contractions
Severe genital bleeding
Shock
Pelvic pain
Uterine rupture (requiring surgical repair, hysterectomy and/or salpingo-oophorectomy)

Overdosage

Mifepristone

No serious adverse reactions were reported in tolerance studies in healthy non-pregnant female and healthy male subjects were mifepristone was administered in single doses greater than threefold of 600mg for termination of pregnancy. If a patient ingests a massive overdose she should be observed closely for signs of adrenal failure.

The oral acute lethal dose of mifepristone in the mouse, rat, and dog is greater than 1000mg/kg

Misoprostol

Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhea, fever, palpitations, hypotension or bradycardia. Symptoms should be treated with supportive therapy it is not known if misoprostol acid is dialyzable.

However because misoprostol is metabolized like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage.

Femiclean Kit: Combipack of Mifepristone & Misoprostol Tablets