A Kare online USA
A-Kare online USA Each kit of A Kare contains the tablet of mifepristone 200mg to be given orally and four tablets of misoprostol 200mg to be given vaginally for the medical termination of pregnancy up to nine weeks, this kit has been developed per guidelines issued by the Royal College of Obstetricians and gynecologists, online USA,
The anti-progestational activity of mifepristone results from competitive interaction with progesterone progesterone-receptor sites Based on studies with various doses in several species (mouse, rat, and monkey), the compound inhibits the activity of endogenous or exogenous progesterone resulting in the termination of pregnancy
Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrium and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins.
Prostaglandin El causes myometrial contractions by interacting with specific receptors on myometrial cells. This interaction results in a change in calcium concentration, thereby initiating made contraction. By Interacting with prostaglandin receptors, misoprostol causes the cervix to soften and the uterus to contract, resulting in the expulsion of the internal contents.
Absorption Mifepristone Action Following oral administration of a single dose of 600mg mifepristone is rapidly absorbed with a peak plasma concentration of 1.98 mg/l occurring approximately 90 minutes after ingestion. The absolute bioavailability of a 20mg oral dose is 69%
Distribution Mifepristone SE bound to plasma protein, albumin, and alpha 1-acid glycoprotein Binding to the later protein is steerable and the drug displays nonlinear kinetics with respect to plasma concentration and clearance Following a distribution phase, elimination of mifepristone is slow at first (50% eliminated between 12 and 72 hours) and then becomes more rapid with a terminal elimination half-life of 18 hours
Metabolism of mifepristone is primarily via pathways involving N- Demethylation and terminal hydroxylation of the 17-propynyl Chan. The vitro studies have shown that CYP450 344 is primarily responsible for metabolism. The three major metabolites identified in humans are (1) RU 42 633 most widely found in plasma, is the N rionodemethyd metabolic (2) RU 42 848, which results from the loss of two methyl groups from the 4-diacetyl aminophenyl in position 11B, and RU 42 68 which results from terminal hydroxylation of the 17-propynyl chain
Excretion By 11 days, after a 600 mg dose of a titrated compound, 83% of the drug has been accounted for by the faeces and 9% by the un Serum levels are undetectable by 11 days
Misoprostol is extensively absorbed and undergoes rapid de-esterification to its free acid, which is responsible for its clinical activity and unlike the parent compound, is detectable in plasma The alpha side chain undergoes beta oxidation and the beta side chain undergoes omega oxidation followed by reduction of the ketone to give prostaglandin F analogues. The compound is a lipophilic methyl ester prodrug and is readily metabolized to the free acid which is the biologically active form. Following oral administration, the plasmo misoprostol levels increased rapidly, with a peak at 30 minutes declined rapidly by 120 minutes and remained low thereafter
In contrast, after vaginal administration, the plasma concentration gradually increased reaching maximum levels after 70-80 minutes and slowly declined with detectable levels present after 6 hours. Vaginal misoprostol l was present in the circulation longer than oral misoprostol(A kare online USA)
and hence, its duration of stimulation of the uterus exceeds that of oral misoprostol.
Vaginal application of misoprostol result in increase and lower peak plasma concentrations of
misoprostol acid than oral administration, but overall exposure to the drug is increased.
A-Kare online USA is indicated for early medical abortion for up to 8 weeks (53 days) of gestation
DOSAGE AND ADMINISTRATION
A-Kare 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 day cycle with ovulation occuring 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 contraceptive device (IUD) should be removed before treatment with mifepristone and misoprostol begins. Pregnancy termination by surgery is recommended in cases when A-Kare fails to cause termination of intrauterine pregnancy
Mifepristone may be administered by or under the supervision of a gynaecologist, who is able to assess the gestational age of an embryo and to diagnose ectopic pregnancies. The gynaecologist 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 equipped to provide blood transfusions and resuscitation, if necessary
The dosage is mifepristone 200 mg orally followed 24-48 hours later by misoprostol 800 mcg (4 tablets of 200 mcg) vaginally.
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 administering misoprostol, a second dose of misoprostol 400 mcg (2 tablets of 200 mcg) may be administered, vaginally or orally depending upon preference and amount of bleeding
Confirmation of termination of pregnancy Patient should be scheduled for a follow-up and return for a follow up visit at approximately 14 days after administration of mifepristone to confirm that the pregnancy is completely terminated and to assess the degree of bleeding Vaginal bleeding is not evidence of the termination of pregnancy. Termination can be confirmed by clinical examination or ultrasonographic
Administration of mifepristone and misoprostol for the termination of pregnancy is contraindicated in patients with any one of the following conditions :
● History of allergy or known hypersensitivity to mifepristone misoprostol or another prostaglandin
● Confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass (the treatment procedure will not be effective to terminate an ectopic pregnancy)
● Chronic adrenal failure
● Hemorrhagic 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 discharge by the administering physician)
WARNINGS AND PRECAUTIONS
The patient should not give Kare to anyone else, A kare online USA has been prescribed for the patient’s specific conditions, 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 contraceptive device (IUD) should be removed before treatment with mifepristone begins Pregnancy termination by surgery is recommended in cases when A-Kare tails to cause termination of intravuterine pregnancy Surgical semination is recommended to manage medal aborion bautent tales
There is no data on the safety and efficacy of mifepristone in women
with chronic medical conditions such as cardiovascular, hypertensive,Hepatic respiratory or renal disease, insulin dependent diabetes mellitus serve anemia heavy smoking. Women who are more than or 35 years of age and who also smoke 10 or more cigarettes per day should be bend with caution because such patenis were generally excluded from clinical trials of mileprisione
Although there is no clinical evidence, the effectiveness of mifepristone may be lower if misoprostol is administered more than two days after mifepristone administration
Vaginal bleeding occurs in almost at patients during the treatment procedure in general, the duration of bleeding and sporting ind as the duration of pregnancy increased Normally it lasts for an average of 9 to 16 days
In some case excessive bleeding may require treatment by vasoconstrictor drugs, curettage, administration of saline infusions and/i or blood transfusions
Prolonged heavy bleeding may be a sign of incomplete abortion or other complications and requires prompt and requires prompt and immediate attention
Infections and sepsis
Cases of serious bacterial infection including very rare cases of fatal septic shock have been reported No causal relationship between these events and use of mifepristone and misoprostol has been established . a sustained fever of 100.4 degree or higher, abdominal pain or pelvic tenderness in the days after medical abortion may indicate infections. A typical presentation of serious infection and sepsis without these but with significant leukocytosis who tachycardia or hemoconcentration can occur
Mipratine is contradicaled in confimed or suspected pregnancy ance e no effective for seminating these pregniz There could be a possibility that a patent who is undergoing a ne abortion could have an undagoed ectopic pregnancy since son Dhe expected sympions of a medical abortion may be similar to to of a ruptured actopic pregnancy The presence of an pregnancy may have been missed even if the patient unde atrasonography prior to being prescribed A-Kare
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 grapefruit 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
Based on in vitro inhibition information, coadministration of mifepristone may lead to an Increase in serum levels of drugs that are CYP 3A4 substrates. 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 CYP 3A4 substrates and have a narrow therapeutic range, including some agents used during general anesthesia
A kare online USA(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 effects on the absorption, blood levels, and antiplatelet effects of therapeutic doses of aspirin. A kare online USA has no clinically significant effect on the kinetics of diclofenac or Ibuprofen. The most common side effects of misoprostol are diarrhea and abdominal pain The side effects may be increased if misoprostol is taken concurrently with antacid Effects of misoprostol are diarrhea and abdominal pain These sides may be increased if misoprostol is taken
Pharmacokinetic studies in patients with varying degrees of renal impairment
showed an approximate doubling of TC and AUC and to normal but no clear correlation between the degrees of impairment and AUC cover 64 years of age, the AUC for misoprostol acid is recommended in older patients with renal impairment, but the dosage may b reduced if the usual dose is not to tolerated
Patients with hepatic disease should receive a decreased dose
Mifepristone is indicated for use in the termination of pregnancy (to 63 days of pregnancy) and has no other approved indication for use during pregnancy Patients who have a risk of fetal malformation resulting from the treatment Surgical termination is recommended to manage medical abortion treatment failure
Several reports in the literature indicate that prostaglandins including misoprostol may have teratogenic effects in human beings skull defects cranial nerve passes, delayed growth, and psychomotor development, facial automation, and defects have all been reported after exposure during the first trimester
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 effects of mifepristone on n infants are unknown breast-feeding women should consult with their doctor to decide if they should discard their breast milk for a few days following administration of the medications
Although it is known whether misoprostol or misoprostol acid is excreted in human milk misoprostol should not be administered to nursing mothers because the potential excretion of misoprostol could cause acid could cause diarrhea in nursing infants
The safety and effectiveness of mifepristone and misoprostol in pediatric patients have not been established
excreted in human milk, misoprostol should not be administered to nursing mothers because the potential excretion of misoprostol acid could cause diarrhea in nursing infants.
PEDIATRIC USE Safety and effectiveness of mifepristone and misoprostol in pediatric
patients have not been established.
The treatment procedure is designed to induce the vaginal bleeding and uterine cramping necessary to produce an abortion. Nearly all of 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 the treatment procedure. Women typically experience abdominal pain, including uterine cramping. Other commonly reported side effects were nausea, vomiting, and diarrhea. Pelvic pain, fainting, headache, dizziness, and asthenia occurred rapidly. The adverse reactions reported during the four hours following administration of misoprostol were judged by women as being more severe than others. The percentage who considered any particular adverse event as severe ranged from two to 35%. After the third day of the treatment procedure, the number of reports of adverse reactions declined progressively, so that by day 14, reports were rare except for reports of bleeding and spotting.
Serious bacterial infection, bleeding, ectopic pregnancies that have
Ruptured and death were reported.
● Gastrointestinal side effects like Alameda, abdominal pain, nausea, flatulence, dyspepsia, headache, vomiting and constipation
● Pain due to uterine contraction
● Severe genital bleeding
● Pelvic pain
● Uterine rupture (requires surgical repair, hysterectomy, and/or salpingo-oophorectomy)
INCIDENCE GREATER THAN 1%
In clinical trials, the following adverse reactions were reported by more than 1% of the subjects receiving misoprostol 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 and placebo.
Causal relationship unknown
The following adverse events were infrequently reported. Causal relationships between misoprostol and these events have not been established but cannot be excluded:
● Body: aches/pains, asthenia, fatigue, fever, rigors, and weight changes
● Skin rash, dermatitis, alopecia, pallor, and breast pain special senses: abnormal taste, abnormal vision, conjunctivitis, deafness, tinnitus, and ear-ache
● Respiratory: upper respiratory tract infection, bronchitis, bronchospasm, dyspnea, pneumonia, and epistaxis
● Cardiovascular chest pain, edema, diaphoresis, hypotension. hypertension, arrhythmia, phlebitis, increased cardiac enzymes, and syncope
● Gastrointestinal: gl bleeding, Gl inflammation /infection rectal disorders, abnormal Hepatobiliary function, gingivitis, reflux, and amylase increase
No serious adverse reactions were reported in intolerance studies in healthy, non-pregnant, female, and healthy male subjects where mifepristone was administered in single doses greater than threefold that recommended for termination of pregnancy. If a patient ingests a massive overdose, she should be observed closely for signs of adrenal failure. The toxic dose of misoprostol in humans has not been determined. Commutative total daily doses of 1600 mcg have been tolerated.
With only symptoms of gastrointestinal discomfort being reported, clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhea, fever, palpitations, hypotension, or bradycardia. It is not known whether dialysis would be an appropriate treatment for overdose. Supportive and symptomatic treatment is advised