cytotec misoprostol

Misoprostol is a synthetic prostaglandin medication used to prevent and treat stomach and duodenal ulcers, induce labor, cause an abortion, and treat postpartum bleeding due to poor contraction of the uterus. Misoprostol is taken by mouth when used to prevent gastric ulcers in persons taking NSAIDs. For abortions it is used by itself and with mifepristone or methotrexate. By itself, effectiveness for abortion is between 66% and 90%. For labor induction or abortion, it is taken by mouth, dissolved in the mouth, or placed in the vagina. For postpartum bleeding it may also be used rectally.

Labor induction

Misoprostol is commonly used for labor induction. It causes uterine contractions and the ripening (effacement or thinning) of the cervix. It can be less expensive than the other commonly used ripening agent, dinoprostone. Oxytocin has long been used as the standard agent for labor induction, but does not work well when the cervix is not yet ripe. Misoprostol also may be used in conjunction with oxytocin. Between 2002 and 2012, a misoprostol vaginal insert was studied, and was approved in the EU. It was not approved for use in the United States, and the US FDA still considers cervical ripening and labor induction to be outside of the approved uses for misoprostol, because no company has sent the FDA scientific proof that misoprostol is safe and effective for these uses.

Abortion

Misoprostol is used either alone or in conjunction with another medication (mifepristone or methotrexate) for medical abortions as an alternative to surgical abortion. Medical abortion has the advantage of being less invasive, and more autonomous, self-directed, and discreet. It is preferred by some women because it feels more "natural," as the drugs induce a miscarriage. It is also more easily accessible in places where abortion is illegal. The World Health Organization provides clear guidelines on the use, benefits and risks of misoprostol for abortions. Misoprostol is most effective when it is used in combination with methotrexate or mifepristone (RU-486). Mifepristone inhibits the signals of pregnancy hormones, eventually causing the uterine lining to degrade, similar to a period, which cause the embryo to detach from the uterus walls.[citation needed] Misoprostol then dilates the cervix and induces muscle contractions which clear the uterus.[citation needed] Misoprostol alone is less effective (typically 88% up to eight-weeks gestation). It is not inherently unsafe if medically supervised, but 1% of women will have heavy bleeding requiring medical attention, some women may have ectopic pregnancy, and the 12% of pregnancies that continue after misoprostol failure are more likely to have birth defects and are usually followed up with a more effective method of abortion. Most large studies recommend a protocol for the use of misoprostol in combination with mifepristone. Together they are effective in around 95% for early pregnancies. Misoprostol alone may be more effective in earlier gestation. WHO guidelines recommend for pregnancies up to 12 weeks to use 12 tablets of 200 mcg (micrograms). The woman should put 4 tablets of misoprostol under the tongue or far up the vagina and let them dissolve for 30 minutes. The woman should wait 3 hours and repeat with 4 pills under the tongue or in the vagina for 30 minutes. She should wait 3 hours and repeat once more. It works in 90% after first attempt and, in case of failure, the attempt may be repeated after a minimum of 3 days.[citation needed] Misoprostol can also be used to dilate the cervix in preparation for a surgical abortion, particularly in the second trimester (either alone or in combination with laminaria stents). Vaginal misoprostol can also be used to facilitate intrauterine device insertion after previous insertion failure. Misoprostol by mouth is the least effective treatment for producing complete abortion in a period of 24 hours due to the liver's first-pass effect which reduces the bioavailability of the misoprostol. Vaginal and sublingual routes result in greater efficacy and extended duration of action because these routes of administration allow the drug to be directly absorbed into circulation by bypassing the liver first-pass effect. Hematocrit or Hb tests and Rh testing are recommended before use for abortion confirmation of pregnancy. Following use, it is recommended that people attend a follow-up visit 2 weeks after treatment. If used for treatment of complete abortion, a pregnancy test, physical examination of the uterus, and ultrasound should be performed to ensure success of treatment. Surgical management is possible in the case of failed treatment.

Early pregnancy loss

Misoprostol may be used to complete a miscarriage or missed abortion when the body does not expel the embryo or fetus on its own. Compared to no medication or placebo, it could decrease the time to complete expulsion. Use of a single dose of misoprostol vaginally or buccally is preferred, with additional doses as needed. It also can be used in combination with mifepristone, with a similar regimen to medical abortion. Misoprostol is regularly used in some Canadian hospitals for labour induction for fetal deaths early in pregnancy, and for termination of pregnancy for fetal anomalies. A low dose is used initially, then doubled for the remaining doses until delivery. In the case of a previous Caesarian section, however, lower doses are used.

Postpartum bleeding

Misoprostol is also used to prevent and treat post-partum bleeding. Orally administered misoprostol was marginally less effective than oxytocin. The use of rectally administered misoprostol is optimal in cases of bleeding; it was shown to be associated with lower rates of side effects compared to other routes. Rectally administered misoprostol was reported in a variety of case reports and randomised controlled trials. However, it is inexpensive and thermostable (thus does not require refrigeration like oxytocin), making it a cost-effective and valuable drug to use in the developing world. A randomised control trial of misoprostol use found a 38% reduction in maternal deaths due to post partum haemorrhage in resource-poor communities. Misoprostol is recommended due to its cost, effectiveness, stability, and low rate of side effects. Oxytocin must also be given by injection, while misprostol can be given orally or rectally for this use, making it much more useful in areas where nurses and physicians are less available.

Adverse effects

The most commonly reported adverse effect of taking misoprostol by mouth for the prevention of stomach ulcers and abortion is diarrhea. In clinical trials, an average 13% of people reported diarrhea, which was dose-related and usually developed early in the course of therapy (after 13 days) and was usually self-limiting (often resolving within 8 days), but sometimes (in 2% of people) required discontinuation of misoprostol. The next most commonly reported adverse effects of taking misoprostol by mouth for the prevention of gastric ulcers are: abdominal pain, nausea, flatulence, headache, dyspepsia, vomiting, and constipation, but none of these adverse effects occurred more often than when taking placebos. In practice, fever is almost universal when multiple doses are given every 4 to 6 hours.[citation needed] There are increased side effects with sublingual or oral misoprostol, compared to a low dose (400 ug) vaginal misoprostol. However, low dose vaginal misoprostol was linked with low complete abortion rate. The study concluded that sublingually administered misoprostol dosed at 600 ug or 400 ug had greater instances of fever and diarrhea due to its quicker onset of action, higher peak concentration and bioavailability in comparison to vaginal or oral misoprostol. For the indication of medical abortion, bleeding and cramping is commonly experienced after administration of misoprostol. Bleeding and cramping is likely to be greater than that experienced with menses, however, emergency care is advised if bleeding is excessive. Misoprostol should not be taken by pregnant women with wanted pregnancies to reduce the risk of NSAID-induced gastric ulcers because it increases uterine tone and contractions in pregnancy, which may cause partial or complete abortions, and because its use in pregnancy has been associated with birth defects. All cervical ripening and induction agents can cause uterine hyperstimulation, which can negatively affect the blood supply to the fetus and increases the risk of complications such as uterine rupture. Concern has been raised that uterine hyperstimulation that occurs during a misoprostol-induced labor is more difficult to treat than hyperstimulation during labors induced by other drugs. Because the complications are rare, it is difficult to determine if misoprostol causes a higher risk than do other cervical ripening agents. One estimate is that it would require around 61,000 people enrolled in randomized controlled trials to detect a difference in serious fetal complications and about 155,000 people to detect a difference in serious maternal complications.

Mifepristone

Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of pregnancy. It is also effective in the second trimester of pregnancy. Effectiveness should be verified two weeks after use. It is taken by mouth. Common side effects include abdominal pain, feeling tired, and vaginal bleeding. Serious side effects may include heavy vaginal bleeding, bacterial infection, and birth defects if the pregnancy does not end. If used, appropriate follow up care needs to be available. Mifepristone is an antiprogestogen. It works by blocking the effects of progesterone, making both the cervix and uterine vessels dilate and causing uterine contraction. Mifepristone was developed in 1980 and came into use in France in 1987. It became available in the United States in 2000. It is on the World Health Organization's List of Essential Medicines. Mifepristone was approved by Health Canada in 2015 and became available in Canada in January 2017. Cost and availability limits access in many parts of the developing world.

Abortion

Mifepristone followed by a prostaglandin analog (misoprostol or gemeprost) is used for medical abortion. Medical organizations have found this combination to be safe and effective. Guidelines from the Royal College of Obstetricians and Gynaecologists describe medication abortion using mifepristone and misoprostol as effective and appropriate at any gestational age. The World Health Organization and the American Congress of Obstetricians and Gynecologists recommend mifepristone followed by misoprostol for first- and second-trimester medical abortion. Mifepristone alone is less effective, resulting in abortion within 1–2 weeks in anywhere from 54% to 92% of pregnancies, according to review of 13 studiesMifepristone alone results in abortion within 1–2 weeks in 54% to 92% of pregnancies. The effectiveness increases to greater than 90% if misoprostol is given after the mifepristone. There is no evidence that the effects of mifepristone can be reversed, although some anti-abortion groups claim that it can be reversed by giving progesterone. Researchers in the United States initiated a trial of the so-called "reversal" regimen in 2019, but stopped prematurely due to serious safety concerns about using mifepristone without follow-up misoprostol. Giving progesterone has not been shown to halt medication abortion, and not completing the combination regimen of mifepristone and misoprostol may cause serious bleeding. In those who continue pregnancy after use of mifepristone together with misoprostol for termination, birth defects may occur. Exposure to a single large dose of mifepristone in newborn rats was not associated with any reproductive problems, although chronic low-dose exposure of newborn rats to mifepristone was associated with structural and functional reproductive abnormalities. Studies in mice, rats, and rabbits revealed developmental abnormalities for rabbits, but not rats or mice.

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