Information AboutRu486 |
| CATEGORIES ABOUT MIFEPRISTONE | |
| sex hormones | |
| abortifacients | |
| antiandrogens | |
| antiglucocorticoids | |
| methods of abortion | |
Mifepristone is a synthetic Steroid with anti-progestagenic and anti-glucocorticoid effects. It is useful in humans as an Abortifacient in the first two months of pregnancy, as well as medical treatment for certain endocrine conditions. During early trials, it was known as '''RU-486''' after its designation at the Roussel Uclaf company, which designed the drug. The drug was initially made available in France , but other countries then followed suit, often amid controversy. In the United States it is made by Danco Laboratories under the tradename '''Mifeprex'''. Since its FDA approval in 2000 , six women in the US and one in Canada have died following medical abortions, causing some medical abortion providers to stop using the method of intra-vaginal placement of the second drug, misoprostol. Two Anti-abortion Senators have introduced legislation calling for an immediate ban on the sale of Mifeprex, pending FDA review. 12 CHEMICAL DESCRIPTION Mifepristone is a light yellow powder, highly soluble in Methanol and only poorly soluble in water. Its structural name is 11β- {Link without Title} -17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one. Its Empirical Formula is C29H35NO2 PHARMACOLOGY During early Pregnancy , the Endometrium is dependent upon progestagenic support from the Corpus Luteum . Mifepristone acts as a competitive inhibitor at the Progesterone receptor and thus removes this basis for support. In addition, it sensitises the Myometrium to the contraction-inducing activity of prostaglandins. It is also an inhibitor of glucocorticoid action and has weak effects at the Androgen receptor. USES RU-486 is sold by Danco Laboratories and is approved to terminate pregnancy up to 49 days after the beginning of the latest menstrual cycle. It blocks a hormone required to sustain a pregnancy. When followed two days later by another medicine, Misoprostol , to induce contractions, the pregnancy is terminated. Other uses include in cases of surgically intractable Cushing's Disease or Cushing's Syndrome , and other progestagen or glucocorticoid secreting tumours. It is Contraindicated in cases of Ectopic Pregnancy , adrenal failure, hemorrhagic disorders, anticoagulant or Corticosteroid therapy. Side effects include an expected amount of abdominal pain and vaginal bleeding, with the possibility of Nausea , Vomit ing and Fever . Incomplete termination of a pregnancy would require further intervention by a doctor (such as Vacuum Aspiration ). SAFETY The number of patient fatalities in mifepristone abortions is estimated at 1 in 200,000, about double the rate for Suction-aspiration Abortion s of comparable terms, and about equal to the combined early and late term fatality rates for vacuum aspiration abortion.3 By comparison, illegal abortions lead to 1 death in 3,000 abortions, and childbirth results in death in 1 out of every 14,300 pregnancies for western women. Deaths in childbirth are significantly more common in less developed parts of the world. In comparison, less controversial drugs such as Viagra and Claritin cause many more adverse reactions.4 Opponents of the drug have claimed that its approval was "fast tracked" under sub-section H in the FDA approval process. However sub-section H actually has two sub-parts. The first is to rush experimental drugs, such as aggressive HIV and cancer treatments to the market as the expediency of their approval is deemed to be vitally important due to the rapid decline of many of the potential patients. The relevant part of sub-section H applies to drugs that must meet more rigorous standards and are subjected to distribution restrictions. Mifepristone was approved under this second part of sub-section H. The result is that women now must receive the drug directly from their doctor; they may not pick it up at a pharmacy.56 Recently, the FDA has released information about five deaths of women who had previously taken mifepristone. These deaths all occurred after the administration of the second medication, Misoprostol , while completing the Off-label dosing regimen consisting of 200 mg of oral mifepristone followed by 800 mcg of intra-vaginally placed misoprostol. This off-label method of administration of mifepristone has been shown to be effective in Clinical Trial s and has been shown to have a lower risks of side effects. One of the reported deaths occurred due to the rupturing of an Ectopic Pregnancy . Termination of ectopic pregnancies using mifepristone is not recommended by its U.S manufacturer, Danco Laboratories, or the FDA. The FDA has concluded that there is no established Causal Link between the deaths and mifepristone.7 On March 17 , 2006 , the FDA reported two additional deaths following medical abortions.8 However, on April 10 , 2006, the FDA declared one of these deaths unrelated to mifepristone use. The other death has not yet been confirmed either way. 9 Pro-life activists and physicians sometimes suggest that an abortion will increase the risk of Breast Cancer and Depression in women. These statements have been widely refuted by the National Breast Cancer Centre10, the National Cancer Institute11, and the American Psychological Association.12 POLITICS Many Pro-life / Anti-abortion groups in the US and elsewhere actively campaign for the withdrawal of mifepristone, citing either ethical issues of abortion or the above-mentioned safety concerns over the drug itself and possible associated deaths. In the US, the proposed Holly's Law is the princible result of this effort. Critics of this law claim that a drug with an identical record for any other purpose would not prompt such action. The issue has now taken on political complexity with both pro-life and Pro-choice campaigners involved. HISTORY The compound was discovered by researchers at Roussel Uclaf of France in 1980 while studying glucocorticoid receptor antagonists. Clinical testing began in 1982 . It was first licensed in France in 1988 , for use in combination with prostaglandin. Then on October 26 of that year, Roussel Uclaf stated that it would abandon distribution of the drug. It bowed to pressure from the government of France two days later to resume distribution. Mifepristone was approved in a number of other European countries as well, starting with the United Kingdom and Sweden in 1991 and followed by Germany in 1992 and most other European countries in 1999 . Early research was difficult, as Roussel Uclaf did not seek U.S. approval. It was further interrupted when the first Bush administration banned the importation of mifepristone in 1989 . This ban was not reversed until 1993 . In 1994 , Roussel Uclaf gifted the U.S. drug rights to the Population Council and the drug went on approvable status from 1996 . Production was intended to begin through the Danco Group in 1996 but they withdrew briefly in 1997 , delaying availability again. It was approved by the U.S. Food And Drug Administration (FDA) in September 2000 . USAGE IN AUSTRALIA AND NEW ZEALAND Mifepristone was effectively banned in Australia in 1996 in a compromise by the Howard Government with conservative Independent Senator for Tasmania Brian Harradine to amend the law to require ministerial approval of RU 486 in exchange for his support for the part sale of the then fully state-owned telecom company Telstra . In late 2005, a Private Member's Bill co-sponsored by Lyn Allison , Fiona Nash , Claire Moore and Judith Troeth was introduced to the Australian Senate to remove this statutory provision and transfer the power of approval to the Therapeutic Goods Administration . The move caused much debate in the Australian media and amongst politicians. The Bill attracted public support from the Democrats , Australian Greens and several individual members of the Labor , Liberal and National parties. Neither the Labor Opposition nor the Coalition Parties took a party stand in favour or in opposition of the Bill and allowed for a Conscience Vote . The Family First Party and Coalition Senators Barnaby Joyce , Bill Heffernan and Ron Boswell signalled their strong opposition. The Health Minister Tony Abbott , a pro-lifer, was targeted by supporters of the Bill. The Bill passed the Australian Senate13 on 10 February 2006 , causing Minister Abbott to label it a no confidence vote in him and the Government14. The Prime Minister disagreed, and indicated that the Senate vote was not a vote of no-confidence in Minister Abbott or government ministers.15 The Australian House Of Representatives has considered the bill, and two amendments proposed during the debate, rejecting the both of them, and passing the bill unamended16. The bill will award final-say on the drug's use to the TGA. If approved by the TGA, the availability of the drug may be assisted with listing on the Pharmaceutical Benefits Scheme . In New Zealand , pro-choice doctors established an import company, Istar, and submitted a request for approval to MedSafe, the New Zealand pharmaceutical regulatory agency. After a court case brought by Right to Life New Zealand failed, use of the abortion drug was permitted. NON-ABORTION USAGE Mifepristone has been investigated in the treatment of Cushing's Syndrome , Endometriosis , and a number of Cancer s. SIDE EFFECTS Usual: Nausea, vomiting, diarrhea, headache, dizziness, and fatigue may occur. Rare: Bleeding and cramping are expected during this treatment. Usually, the symptoms mean the drugs are working. However, sometimes a woman can have cramps and bleeding and still be pregnant. Bleeding and spotting may last up to 30 days, and may be greater than a normal, heavy period. In a very few cases, this bleeding will need to be stopped by performing a surgical procedure. Serious: fever, fainting, vaginal discomfort or itching, unusual vaginal discharge, fast heartbeat, stomach/abdominal pain or tenderness, any other sign of infection. A patient noticing other effects not listed above should contact their doctor or pharmacist. NOTES AND REFERENCES EXTERNAL LINKS
|
|
|