The Approval of the Oral Abortion Pill Mefeego Pack and Remaining Issues

Japan's abortion situations-- Past, Present, and Future

Linepharma's Mefeego Pack, containing one Mifepristone and four Misoprostol tablets, has been called "Japan's first oral abortion pill. "Japan's first abortion pill" was Preglandin (ingredient name: gemeprostol), a transvaginal mid-term abortion pill approved in 1984. Since then, for a long time in Japan, early-term abortions were mainly performed by curettage, while this archaic vaginal suppository was for later abortions.

Until recently, Japanese people were not much interested in oral abortion pills: in a 2014 survey of Japanese women in general, a majority said they had never heard of abortion pills, and more than one-third said that they could not distinguish them from emergency contraceptives, whereas less than 10% of respondents correctly recognized that abortion pills were not on sale in Japan and put on sale in foreign websites. The U.S. medical consulting firm that conducted the survey was also involved in the 2017 approval of the manual aspirator Women's MVA System. Japan's Galapagosized abortion care was slowly beginning to change due to these external pressures.

Japan is one of the few countries where abortion came before contraception. Although abortion was legalized soon after the Second World War and later was simplified so that it could be performed virtually at the discretion of a single doctor. In contrast, oral contraceptives did not come until 1999 and are not still very popular.

The conventional lack of interest in oral abortion pills in Japan is due in part to a lack of education, which has led to a lack of awareness on the part of women to control their pregnancies, as well as a social problem in which the barriers to accessing contraceptive information and methods are too high. For example, both contraceptives and emergency contraceptives require a "doctor's prescription" in Japan and are extremely expensive. For young women who have never been pregnant, going to an obstetrician/gynecologist can be very uncomfortable, and even the cheapest monthly birth control pills cost 2,000 to 3,000 yen, while an emergency contraceptive pill costs 10,000 to 20,000 yen.

Nevertheless, abortion pills gathered attention in April 2021 when news broke that Linepharma would apply for approval of "Japan's first oral abortion pill. Female journalists indeed showed a high level of interest personally, and I believe women's movements like ASAJ wielded influence by providing information and lobbying lawmakers on abortion pills around 2020.

In December 2021, Linepharma K.K. applied for approval of a combination pack for oral abortion consisting of two drugs, Mifepristone and Misoprostol. The following year, the Pharmaceuticals and Medical Devices Agency (PMDA) conducted a review and issued a report in November stating that the approval was appropriate.

Linepharma's oral abortion drug, named "Mefeego Pack," was finally approved on April 28, 2023, after deliberations by the First Division of the Pharmaceutical Affairs and Food Sanitation Council of the MHLW at the end of January 2023, a month of public comment, and deliberations by a higher-level Pharmaceutical Affairs Subcommittee. In addition to being strictly controlled as a "deleterious" drug, the conditions of approval stated that the drug "must be administered under the confirmation of a designated doctor under the Maternal Body Protection Law" and "must be used for the time being in a hospitalized facility (hospital or clinic) where hospitalization is possible, and after Misoprostol administration, the patient must remain in a hospital or on standby until the patient expels the pregnancy.

Only the designated doctors under the Maternal Body Protection Law can perform abortions in Japan. There is no coverage by health insurance, and individual medical institutions can determine the method and fee of abortion. In addition, women have to get spousal consent before taking abortion pills. Furthermore, even if they ease regulations in the future, there is still a risk of violating the crime of self-abortion under criminal law if the person performing the abortion takes the abortion pill by themselves.

Mefeego Pack became available on May 16, 2023, and medical institutions wishing to handle it can take Linepharma's e-learning course to register. However, it is not yet ready for accessible use. I pointed out six problems below:

First, there is a lack of providers: as of June 15, 2023, only 14 medical institutions appear on Linepharma's website, "Find Hospitals and Clinics Where You Can Ask About Abortion Pills." Since this is a free medical service, they may be waiting to see how other hospitals will operate, but some parts of Japan have no medical institutions offering the service. It seems unlikely that the system will spread rapidly.

Second, the fees are likely to be high. Only two of the 14 locations listed above clearly indicate their prices on the websites. One sets the flat fee of 128,000 yen for surgical or medical abortions, while the other charges 89,000 yen, including the cost of a preliminary medical examination. Although Linepharma has not disclosed the wholesale price of the abortion pill, the Japanese Association of Obstetricians and Gynecologists assumes the cost of the medicine is about 50,000 yen to justify the price at medical institutions as about 100,000 yen, including the pill, consultation, examination, and treatment in case of failure. It is said to be slightly cheaper than surgery, but the price is left to the judgment of individual medical institutions and cannot be predictable.

Third, hospitalization or waiting in the hospital "until the pregnancy expels" is mandatory, although only for a while. Since the conventional abortion procedure for early pregnancy in Japan has been a one-day operation, if "hospitalization" is required for those who wish to take the medicine, there will be people who give up. It is also unclear whether they can stay in a private room or whether the patient can be with a chaperone. If it takes longer to complete the abortion, the cost of hospitalization may increase.
There are also concerns about whether the patient will experience emotional distress from encountering other expectant mothers and newborns because of the long time spent in the medical facility. Another problem is that, unlike surgery, you are awake, but they don't offer mental health care.

Furthermore, in the case of in-hospital waiting, there is no indication of rules for what to do "if the pregnancy has not been expelled" by the end of clinic hours. The advantage of the abortion pill is that it "de-medicalizes" abortion. There should be an option to take the Misoprostol alone, which expels the pregnancy product, at home.

Fourth, there is no option to complete the abortion with the medication alone as much as possible by giving additional doses of Misoprostol; the WHO's 2022 "Guidelines for Abortion Care" states that you can consider "repeated doses of Misoprostol application if necessary to complete the abortion..." However, giving additional Misoprostol is not an option for Japanese doctors who only perform the surgery if it fails. Giving additional Misoprostol should be an option, as this would increase the number of people who could complete the abortion with the drug alone.

Fifth, ultrasound (echocardiography) is a requirement for taking the medication in Japan. After the Corona disaster, "self-administered abortion," where the patients have the medicine at home very early in the pregnancy without requiring an echo, has become widespread in other countries. The International Federation of Gynecology and Obstetrics (FIGO) encouraged "online prescription of abortion pills and self-administered abortion in early pregnancy" as a temporary measure in March 2020, when WHO declared the COVID-19 pandemic, and after confirming that this method was used safely and effectively, in March 2021 it "made this method permanent The statement "this method should be made permanent" was issued in March 2021.

Although ultrasound can confirm pregnancy around the 6th week, the latest pregnancy test reacts at 4 to 5 weeks. Recently, medical abortion (VEMA), performed at a very early stage when ultrasound cannot confirm the pregnancy, has shown promise as a beneficial method that hastens the completion reduces risks, and serves as a screening test for ectopic pregnancies.

Sixth, abortion pills are also effective in treating patients with comorbid abortions, but this is not an option in Japan. Only to offer the highly invasive "surgery" is nonsense when you can use the pill for comorbid miscarriages.

Since there are no uniform guidelines for the handling of abortion pills in Japan, there should be a wide range of discretion for individual doctors. They should put the patient first, demonstrate "professional autonomy," and improve access to abortion pills.

Evidence that Mifepristone is a "deleterious drug"？

I received a response from the MHLW, but......

The abortion drug Mefeego Pack, approved in Japan, has been designated a "deleterious drug" by the Japanese Ministry of Health, Labor, and Welfare. According to them, Mifepristone and Misoprostol are both "deleterious" drugs. When I asked for scientific evidence to support this, I received a response.

However, there is a part of their response that I did not understand, so I will translate it into English below.

A part of their answer I couldn't comprehend:

(i) Mifepristone

(1) The results of embryo-fetal development studies indicate that the non-toxic dose of mifepristone is 0.5 mg/kg/day for mice, 0.5 mg/kg/day for rats, and 0.25 mg/kg/day for rabbits, and that these human equivalent doses are lower than the clinical dose (4 mg/kg/day when the human body weight is 50 kg) These human equivalent doses are lower than the clinical dose (4 mg/kg/day for a 50 kg human body weight).

(See the Mefeego Pack Drug Interview Form "IX. Toxicity Studies (5) Reproductive and Developmental Toxicity Studies," p. 85)

On the interview form referred, I bolded the numbers where they matched.

(1) Female rat fertility and early embryogenesis to implantation study

Mifepristone was administered to female SD rats at a dose of 0.5 mg/animal/day (approximately 2.5 mg/kg/day) for 24 days starting 8 days before mating, and pregnancy status was evaluated the day after the last dose84) . Compared to the control group, there was no effect on the number of mated animals or pregnancy rate, but the number of implantations per pregnant rat was significantly reduced.
　Tamura et al. conducted a female fertility study in which female SD rats were treated with mifepristone at doses of 0, 0.8, 4, or 20 mg/kg/day from 2 weeks prior to mating until 7 days of gestation85). The 20 mg/kg/day group showed persistent keratinization of the vaginal mucosa and arrested sexual cycle. 20 mg/kg/day for the entire period The 20 mg/kg/day group mated 10/10, all were infertile; the 20 mg/kg/day pre-mating only group mated 10/10, with 6/10 pregnant animals and increased preimplantation embryo loss rate.
　The number of pregnant animals in the 20 mg/kg/day post-mating group was 0/10. 4 mg/kg/day pre-mating group showed no effect on the number of mated animals, pregnant animals, or absorbed embryos, while the post-implantation embryo loss rate increased during the entire period and in the post-mating group. Since the cessation of the sexual cycle, the decrease in the number of pregnant animals and the number of implants, and the increase in the number of absorbed embryos were due to the pharmacological effects of mifepristone, 20 mg/kg/day was considered a non-toxic dose.

(2) Embryo-fetal development studies in mice, rats, and rabbits

A study on embryo-fetal development of pregnant CD1 mice, SD rats, and HY rabbits was conducted using repeated oral administration of mifepristone during organogenesis.86),87),88) In all three species, an increase in the number of absorbed embryos (≥ 0.5 mg/kg/day in mice, ≥ 1 mg/kg/day in rats, ≥ 2 mg/kg/day in rabbits) was observed. 2 mg/kg/day or more in rabbits) were observed in all three animal species. However, no teratogenicity was observed in mice or rats. Some morphological abnormalities were observed in fetal rabbits, but the frequency of occurrence of these fetal abnormalities varied, and they were also seen in the control group, so the relationship to dosing was not clear. The non-toxic dose for the mother was considered to be 0.5 mg/kg/day for mice, 0.5 mg/kg/day for rats, 0.25 mg/kg/day for rabbits, and for embryos and fetuses, 2 mg/kg/day for mice and rats and 1 mg/kg/day for rabbits.

The first thing I couldn't understand was that at the end of (1), it says the non-toxic dose is 20 mg/kg/day, so isn't 4 mg/kg/day (i.e., the value for a 50 kg person given 200 mg of Mifepristone). This is smaller than the non-toxic dose, so Mifepristone should be non-toxic at least for this?

　Also, (2) is a "repeated dose" experiment, but in humans, Mifepristone is only given once. There is no way it can be administered repeatedly. Wouldn't it be better to compare the results with those in which all animals were given only one dose in accordance with the human dosage?

　Furthermore, (2) is an experiment looking at the effects on the embryo/fetus, and suddenly there is talk of a "non-toxic dose to the mother animal".

It is strange. I'll inquire again next week.

A big but awkward step forward

My report

In Japan, the Mefeego Pack, a combi-product of one Mifepristone and four Misoprostol tablets, was launched on May 16, 2023, and the Japan Women's Foundation's Dr. Miho Uchida's clinic began offering "oral abortion pills" for the first time in Japan on Thursday, May 25, 2023.

As far as we could confirm on May 27, 11 hospitals or clinics joined the providers listed on the website of the manufacturer Linepharma K.K. as institutions that can handle this drug, however on Monday morning, all the other clinics that followed the lead of Dr. Uchida's Fides Ladies Clinic disappeared from the list.

As of the time of our review over the weekend, there was no detailed information on the abortion pill offerings on the websites of these ten medical institutions, so we assume that either Linepharma has decided to withhold the listings until they provide more detailed information, or that each of the clinics, aware of their lack of preparation, has voluntarily suspended their listings.

Anyway, because abortion pills are provided outside the insurance system and not covered by any public funds, women must pay the equivalent of the most expensive legal surgical abortion in the world. At Dr. Uchida’s clinic, the total fee for medical abortion is the same for the surgery is set at 99,000 yen.

In Japan, written consent of the spouse is still legally necessary as a pre-condition for any method of abortion. In addition, the patients cannot take abortion pills very early in the pregnancy, as the doctor prescribes the medications only after they could confirm the pregnancy in the uterine by transvaginal ultrasound which means usually after 6th week. However, according to Dr. Christian Fiala of Austria, who spoke at the #Action for Safe Abortion Japan online event on May 28, taking abortion pills very early is effective when an echo test is unavailable. If nothing happens, he says, then one should suspect an ectopic pregnancy and go to a higher-level medical facility. Very early MA also serves as a screening for ectopic pregnancy.

Japanese abortion patients should take both medications in front of a physician, and after taking the misoprostol, they are forced to stay in the medical institution until the pregnancy expels. Many obstetrics and gynecology facilities in Japan are not dedicated to abortion services and often house expectant mothers, new mothers with babies, infertility treatment, and gynecology patients in the same waiting room, which is an uncomfortable place for abortion patients to be. Now, however, abortion patients are required to remain in the hospital for up to eight hours (doctors say 90 % of the cases finish in 8 hours, but what about the remaining 10%!?) after taking the misoprostol. The Ministry of Health, Labor, and Welfare and the Japanese Association of Obstetricians and Gynecologists state that this in-hospital waiting rule is "temporary" and will be lifted once safety is sufficiently confirmed, but the criteria for lifting are unclear.

The JAOG also states that patients who come to the hospital to take Mifepristone on the first day at any time, and Misoprostol two days later at 9:00 a.m. should remain in the hospital until the pregnancy expells and that if the expulsion is not completed by 5:00 p.m., surgery will be performed next day or later. However, whether the patient will be hospitalized for a fee or sent home at their own risk is not explained clearly.

Because the Japanese health insurance system or any public funds do not cover abortion costs, women must pay the equivalent of the most expensive legal surgical abortion in the world. Some people may have to pay for hospitalization, backup surgeries, and multiple hospital visits out of their pocket.

"The approval of the abortion pills in Japan means that women now have more options," says Dr. Uchida. ”From now on, Japanese women no longer have to risk their lives to use foreign abortion pills by self-determination. Now a qualified doctor can fully explain the options and risks of abortion and make the best choice for her is a step forward for Japan from the perspective of 'reproductive rights'."

But it will likely take a little longer for Japan to achieve reproductive rights that guarantee women themselves to make the best choices for themselves.

Product information for MEFEEGO Pack, a combi-pack product of Mifepristone and Misoprostol for Japanese market

One of the misteries that occationally happens in MHLW sites

The site I could find easily yesterday suddenly disappeared! It was a product information of MEFEEGO Pack with the sign of "Deleterious product." I searched the site of the Ministry of Health, Labour and Welfare and found a new URL for the product information with the "deleterious" sign:
https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/841049_249910AX1028_1_02

Along the process, I also found a new "Report of Deliberations" issued on April 26, 2023 by the Drug Evaluation and Administration Division of the Pharmaceuticals and Consumer Health Bureau of MHLW. The two-page report was added on top of the "Report of Examination" provided at the time of gathering pubic comments during last February.
https://www.pmda.go.jp/drugs/2023/P20230501001/841049000_30500AMX00126_A100_1.pdf

The translated content of this added document includes as follows:(original in Japanese)

Report of Deliberations
April 26, 2023
Drug Evaluation and Control Division, Pharmaceuticals and Consumer Health Bureau
［Marketing Name］ Mefeego Pack
［Generic Name] Mifepristone, Misoprostol
[Applicant's Name] Linepharma K.K.
［Date of Application] December 22, 2021
［Results of deliberation］
The First Subcommittee of the Pharmaceutical Affairs and Food Sanitation Council held on January 27, 2023 approved this item and decided to submit it to the Pharmaceutical Affairs Subcommittee of the Pharmaceutical Affairs and Food Sanitation Council.
At the Pharmaceutical Affairs Subcommittee meeting held on April 21, 2023, it was decided that approval is acceptable on the assumption that the following handling will take place.

• For the time being, the patients should be admitted to a facility with beds that can accommodate them or be treated on an outpatient basis (in-hospital standby is mandatory) until an appropriate system for emergency use has been established. Regarding the "period of time until the appropriate system for use is established," a notice will be issued stating that sufficient post-marketing surveillance and research will be conducted to evaluate the appropriate medical coordination system, and the results will be used as the basis for consideration and decision making.

• Regarding distribution and use management, a procedure manual should be established to require the manufacturer/distributor and each medical institution to report monthly to prefectural medical associations the volume of sales and the volume of use (number of abortions), respectively, and the manufacturer/distributor should be required to stipulate this as a "necessary measure" in the conditions of approval. Prefectural medical associations will be required to supervise the reporting by checking the consistency of the content of both reports.

• In order to enhance the provision of correct information, the applicant should prepare materials for designated doctors under the Maternal Body Protection Law (proper use guide), and the MHLW should provide appropriate information for the public(e.g., by creating a website).

This item is not classified as either a biological product or a specified biological product, the reexamination period is eight years, and both the active ingredient and formulation of Mifepristone and the formulation of Misoprostol are classified as deleterious drugs.

［Conditions for approval]
1. A drug risk management plan should be established and properly implemented.
2. Take necessary measures to ensure that the drug is used only by designated doctors under the Maternal Body Protection Law, including the implementation of distribution and other controls in cooperation with related organizations.

The phrase "classified as a deleterious drug" was suddenly added without any explanation, which was not included in the "Review Report" issued by the Pharmaceuticals and Medical Devices Agency on November 9, 2022.

It is quite absurd that the word "deleterious drug" disappeared while public comments were being gathered, yet after two rounds of secret deliberations, when it was finally approved, it turned out to be a "deleterious drug" again.

On Approval of Mefeego Pack to Japan

Original Note by Kumi Tsukahara

On Approval of Mefeego Pack to Japan - What We Can Learn from the Experience of Preglandin Suppository, the Only Approved 2nd-trimester Abortion Drug in This Nation

Transvaginal Abortion Suppository Seen as Promising in the 1970s-1980s

In December 2021, Linepharma K.K., with a British parent company, filed for approval of the oral abortion drug Mefeego Pack, the first oral abortion pill in Japan, but it is not the first abortion drug. Preglandin Vaginal Suppository (chemical name: gemeprost) was the first modern abortion medication in Japan and abroad. Ono Pharmaceutical Co., Ltd. developed and got approval for manufacturing and marketing from the Japanese government in 1984. Since then, this drug has been the primary treatment for second-trimester abortion in Japan.

However, it has been kept as a secret that gemeprost had a high success rate in clinical trials for first-trimester abortion in Japan between 1977 and 1980.

This report reveals the past of vigorous control over Preglandin (gemeprost) for the benefit of a few doctors to call attention to the fate of the newly approved oral pills - Mefeego Pack - will be.

Gemeprost was developed under the name of ONO-802, which has several trade names in other countries, including Cervagem in Sweden and Singapore. When I searched for "ONO-802" up to 1980 in PubMed, I found 11 research articles from 1977 to 1980. Nine of these studies were conducted by Japanese, with two English reports and seven Japanese. Two other studies were conducted abroad and reported in English. Ten out of the eleven studies were related to first-trimester abortions.

For example, Karim et al. of the National University of Singapore, who reported the first clinical trial in 1977, found that 50 women 5 to 14 days over their expected menstrual period received one 1 mg tablet vaginally and were sent home with instructions to insert four suppositories, one every 4 hours and that 46 (98%) successful abortions were confirmed by a pregnancy test two weeks later [1]. The same year, Tominaga Yoshiyuki et al. of Tottori University in Japan reported for the first time as a Japanese that a 0.5 mg or 1 mg vaginal suppository was administered 3 to 5 times every 3 hours to 32 patients within four months of pregnancy, and 30 patients (93.8%) had successful abortions [2].

The women reported various side effects in the 10 studies, but they were considered only transient and treatable. Even in cases where abortions were unsuccessful, the cervical dilating effect of gemeprost was favorably reported as facilitating backup surgical procedures. In addition, there have been several successful cases in which women have self-administered the drug vaginally.

In the late 1970s, no medicines were available anywhere in the world for first-trimester abortion. It was 1982 when the clinical trials of RU-486 (Mifepristone) began in Switzerland, while ONO-802 had reported high success rates in 10 early pregnancy trials by 1980, and all the researchers involved saw it as a promising abortion drug for early pregnancy.

International Attention

In July 1982, an international symposium on Cervagem (gemeprost) was held in Singapore, led by Karim, and scholars participated in the symposium from the United Kingdom, Singapore, Hong Kong, Norway, Sweden, and Japan. The next year, a book entitled "Cervagem" was published, containing a total of 10 presentations and 3 questions from the symposium. Chapter 7, jointly authored by K. Sato, K. Kinoshita, and S. Sakamoto of Japan, is entitled ‘Clinical Study of Cervagem (ONO-802) for Abortion in the First and Second Trimester in Japan.’ It reported the results of clinical trials conducted with ONO-802(gemeprost) at 12 Japanese universities from December 1977 to July 1978 in the first and second trimesters of pregnancy, respectively.

In “Cervagem”, researchers from May-Barker in the U.K. revealed the fact that in 1974 they began working with Japanese researchers at Ono Pharmaceutical Company “to find an effective drug for early miscarriage,” and believing that “this drug should also be a powerful cervical dilator.” ONO-802 is itself an ‘abortion drug’ that artificially causes miscarriage through uterine contractions, and at the same time, it has attracted attention as a ‘cervical dilator’ to ripen and open the cervix as a pre-treatment for surgical abortion.

On the other hand, the Japanese, who had been using laminaria tents mainly for cervical dilation since the 1950s, had no idea of using ONO-802 for cervical dilation, or rather, the method of opening the cervical canal with laminaria before intravaginal administration of this drug is still the current standard practice in Japan.

Lies told in Japan and Abroad

However, in April 1981, the year before the international symposium on Cervagem, Ono had already applied for approval of Preglandin to the Ministry of Health and Welfare of Japan as a dedicated second-trimester abortion drug for use only after the 12th week of pregnancy. The only data submitted with the application were the results of a clinical trial on the second-trimester pregnancy. The results were published in Japanese in the 1981 issue of Obstetrics and Gynecology (No. 10) as “Therapeutic Miscarriage and Cervical Dilation of ONO-802 Vaginal Suppository in the Second Trimester of Pregnancy,” co-authored by 31 doctors from 12 universities in Japan. They entirely omitted the data for the first-trimester abortion which had been already published in the English book.

In August 1982, four months after the international symposium, the Central Pharmaceutical Affairs Council declared that approval was 'appropriate'. In response, the Nihon Keizai Shimbun (Nikkei Asia) reported in its morning edition on September 28 that “The government will soon grant manufacturing approval, and that the MHW intends to approve it as an indication drug that only designated doctors under the Eugenic Protection Law can prescribe limited to the case of a therapeutic abortion in the second-trimester pregnancy,” and added, “Ono has been conducting clinical trials in more than ten foreign countries with the cooperation of WHO. However, since Ono has NO clinical trial data on abortions in the first-trimester pregnancy and on its effects on artificially delivered third-trimester fetuses.” As I mentioned earlier, this is contrary to the fact: clinical trials have been conducted abroad mainly on abortion in the first trimester of pregnancy. For some reason, data on the first trimester of pregnancy was concealed.

Mechanism to Protect the Rights and Interests of the Designated Doctors

However, it took two more years after the news report until the government approved the drug due to lengthy procedures to impose even stricter restrictions. Besides the above requirements, the MHW also specified that the use of the drug must be limited to second-trimester therapeutic abortion to treat a maternal injury or illness, designated it as a deleterious drug, and established its management and handling guidelines, to supervise its quantity, lot numbers, and date of delivery in the aim to prevent illegal use or resale of the drug. After such exceptionally strict regulations, finally, Preglandin was approved as the first abortion drug in Japan on May 30, 1984.

The Nikkei Sangyo Shimbun (Nikkei Business Daily) explained the background of this “exceptional measure” as follows:

“The simplicity of inducing miscarriage without general anesthesia by just inserting a suppository of Preglandin into the vagina every three hours stirred up anxiety in various quarters. Religious groups were concerned that the number of easy abortions would increase, and the designated doctors feared that laypersons and other non-designated doctors could perform abortions."

The newspaper reporter exposed that such a strict and rigorous regulation was so “unusual” that MHW wanted to create a system that would protect the interests of a specific group of designated doctors, the Japan Mothers Protection Association（Current JAOG）.

What Separates Preglandin from Mefeego Pack

Preglandin was filed for approval in 1981, and 40 years later the oral abortion drug of Linepharma was filed for approval in December 2021. During these 40 years, a vast amount of research has accumulated on abortion pills. However, the Japanese designated doctors are once again trying to protect their interests by insisting that only they can prescribe the drug, hospitalization is required, spousal consent is needed, and the fee would be about 100,000 yen（more than US$700）.

However, there is a major difference between the two drugs: at the time of the application for Preglandin in the 1980s, only 125 people participated in the clinical trials, and the safety of this drug had not yet been established, as the problems of uterine rupture later arose. On the other hand, the combi pack that was approved in Japan has been used millions of times even in the U.S. alone. It has myriad evidence of safety and certainty so the WHO has selected abortion pills into the Essential Medicines List since 2005 and included them on its Core List in 2019.

In addition, the situation of women has changed dramatically over the past 40 years: in Japan in the 1980s, pseudo-religious aborted fetal offerings (mizuko kuyo) enjoyed extraordinary prosperity. The religious right made great use of the argument of mizuko kuyo, which considers abortion to be a “crime of women,” and denounced them verbally to impede abortion. For this reason, the view of abortion in public opinion at that time was far harsher than it is today.

The atmosphere of the era of abortion condemnation, in fact, even affected the psychology of some abortion pill developers. Yoshiyuki Tominaga of Tottori University, who is introduced as the “father” of Preglandin testified that he was horrified by the “frighteningly great" effects of this drug and anguished over whether such a medication was allowed to be introduced into the world. On the other hand, Tominaga also stated that “more women would be saved if it were allowed in the early stages of pregnancy as well”. Such views centered on women's health and well-being did not catch Japanese people's attention at the time and were forgotten.

Ten years later, ‘reproductive health and rights’ was proposed at the International Conference on Population and Development in Cairo, Egypt, in 1994, and at the World Conference on Women (Beijing Conference) the following year, “the freedom to decide whether or not to have children, when to have them, and how many to have,” was reaffirmed. In countries where abortion pills had been introduced earlier, the time to finish abortion is becoming shorter, and the stigma of “abortion” is diminishing as women who had used the pills began speaking out about their experiences. Then came the Covid-19 pandemic. The international specialists on reproductive healthcare reaffirmed abortion as essential medical care. Now the International Federation of Obstetrics and Gynecology has issued a statement calling for online prescription and home use of abortion pills to be made permanent. The United Nations has also made it clear that abortion restrictions are a violation of human rights.

In the 21st century, the world's view of abortion has changed dramatically. Knowing this, we should keep a close eye on how Mefeego Pack will be used in Japan.

[i] Karim et al., ‘Menstrual induction with vaginal administration of 16, 16 dimethyl trans-delta2-PGE1 methyl ester(ONO 802),’ Prostaglandins Vol.14 No.3,1977.
[ii] Tominaga et al., Abstract of ‘Basic and clinical study on medical abortion with vaginal administration of 16, 16 dimethyl trans-delta2-PGE1 methyl ester,’ in Japanese, Japan Society of Obstetrics and Gynecology, Vol.29 No.10, 1977.

Japan: Mefeego Pack approved as the first Medical Abortion drug

No one reported anywhere that it was approved as a deleterious drug

bnn.network

ASAJ's Request on "Notes on the Use of Mefeego Packs”

For more available, accessible and affordable abortion pills!

#Action for Safer Abortion (ASAJ) issued a request on May 8, 2023 to the following people and held a press conference on the same day at 11:00 am. This is a private, tentative translation of said request.

May 8, 2023

Mr. Katsunobu Kato, Minister of Health, Labour and Welfare
Mr. Masanobu Ogura, Minister of State for Special Missions, Cabinet Office
Ms. Yumiko Watanabe, Director-General of the Administration for Children and Families
Dr. Yoshiro Matsumoto, President, Japan Medical Association
Mr. Isamu Ishiwata, President, Japan Association of Obstetricians and Gynecologists

#Action for Safer Abortion (ASAJ)
https://www.asaj2020.org/
safeabortion2020@gmail.com

Request on "Notes on the Use of Mefeego Packs

We are a group working for the decriminalization of abortion and improved access to safe abortion. We are submitting a request (*) regarding the document on proper use, etc. published on the website of the Ministry of Health, Labor and Welfare (MHLW) in relation to the approval of the manufacture and sale of drugs for oral abortion.
(*)https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/iyakuhin/topics/infertility_treatment_00001.html, Viewed April 28, 2023

(1) "For the time being until the appropriate system for the use of this drug is established
"For the time being," the MHLW recommends that the period of time spent on evaluation be kept to the minimum necessary, and that subsequent hospital stays be made only when a woman wishes to do so.

(2) Cost Burden
Abortion is a medical treatment that affects the lives, livelihood and health of many people living in Japan.
The Ministry of Health, Labor and Welfare (MHLW) should make abortion either covered by insurance or subsidized by public funds.
Doctors should set accessible fees for abortions using oral abortion pills.

(3) Spousal Consent
Spousal consent should not be required for the use of abortion pills. Maternal Body Protection Laws that require spousal consent for abortion violate reproductive rights.

(4) Provision of Information
The Ministry of Health, Labor and Welfare (MHLW) should provide scientifically based information on oral abortion pills and supervise medical institutions to ensure that they do not disseminate incorrect information.

The end.

Q&A:What is the abortion procedure?

Explanation of the abortion methods by Japan Association of Obstetricians and Gynaecologists

What if the abortion procedure? - JAOG

This is my personal translation from original Japanese version.

Question: What is the abortion procedure?

Answer: There is a big difference between early pregnancy (less than 12 weeks) and pregnancy from 12 to 22 weeks. There is a big difference in the abortion procedures and the subsequent proceedings.

An abortion is performed when the Maternal Body Protection Law applies, and when the pregnancy must be terminated. The procedures differ between early termination (less than 12 weeks) and later termination.

In early termination (less than 12 weeks), the uterine contents are removed by curettage (scraping out the contents) or aspiration (sucking them out with an instrument). In most cases, the contents of the uterus are removed instrumentally under intravenous anesthesia after dilating the uterine opening beforehand. The procedure usually takes only 10 to 15 minutes, with minimal pain and bleeding, and if there are no physical problems, the patient can go home on the same day.

For pregnancies of 12 to 22 weeks, the cervix is dilated in advance, and uterine constrictors *1 are used to artificially induce contractions that cause a miscarriage. Although it varies from person to person, the procedure is physically demanding and usually requires several days of hospitalization. If the abortion is performed after 12 weeks of pregnancy, it is necessary to report the stillbirth to the local government office and obtain a permit for the burial of the aborted fetus.

Most abortions are not covered by health insurance. For abortions performed after 12 weeks of gestation, the financial burden is greater due to the cost of hospitalization as well as the surgical fee. Therefore, if you must choose to have an abortion, it is better to make the decision as early as possible to minimize the various burdens.

Since only "designated doctors" designated by the Maternal Body Protection Law are allowed to perform abortion surgeries, you should undergo the procedure at a medical institution that has a doctor who is designated by the Maternal Body Protection Law. While some foreign countries have marketed early pregnancy abortion pills, they are currently not approved in Japan. There have been reports of heavy bleeding, and the Ministry of Health, Labor and Welfare has issued a warning.

• Adapted from "Adolescent Gynecological Consultation Manual for School Doctors and School Teachers.

"

*1:gemeprost vaginal pessaries

Message from an expert: On approval of Mefeego Pack

Here is an excerpt from the monthly message on May 7 from Tomoko Saotome MD., PhD., the president of the Professional Women's Coalition for Sexuality and Health in Japan.

On April 28, the Japanese government finally approved the oral abortion drug Mefeego Pack for production and marketing in Japan. The drug is a combination pack of the anti-progesterone mifepristone, which interrupts pregnancy, and misoprostol, which causes the uterus to contract after 36 to 48 hours.

Although the Japanese Ministry of Health, Labor, and Welfare only emphasize concerns about side effects, the drug has a long history of use in France and China since 1988 and soon became available in other countries. In Japan, as per clinical trials, the drug is prescribed only during hospitalization and can only be prescribed by doctors designated under the Maternal Body Protection Law who have completed training by the pharmaceutical company Linepharma.

The Maternal Body Protection Law continues to be a barrier for women to access medical abortion, requiring hospitalization and the partner's consent to take the medication. Clinics that do not have inpatient beds will continue to perform surgical procedures because they cannot prescribe for the time being. Even if users find a medical facility where they can obtain oral medications and reach a doctor who can use the drug, it is shocking to face the fact that they have no choice but to be hospitalized.

Confusion will be inevitable for the foreseeable future. Training in the attitude of medical professionals toward medical abortion is also needed. There is a movement to develop a program in our colision based on programs in other countries.

Original in Japanese, translated by Kumi Tsukahara

MHLW of Japan: Oral abortion pills imported by individuals (so-called oral abortion pills) in 2004

Press Release Material still published and referred by media and clinics

Here is my translation of the MHLW's press release material in 2004. The original material is in Japanese.
https://www.mhlw.go.jp/houdou/2004/10/h1025-5.html

October 2004 ＜Press release material
Topics
October 25, 2004
Ministry of Health, Labour and Welfare
Surveillance Guidance and Narcotics Control Division
　Mitsuoka (Ext. 2763)
　Morita (ext. 2762)

Oral abortion pills imported by individuals (so-called oral abortion pills)

　Oral abortion pills, which are not approved in Japan, are known to cause bleeding that sometimes requires surgery, and even in Europe and the U.S., they are drugs that require a doctor's prescription and follow-up care.
Therefore, the Ministry of Health, Labor and Welfare has decided to call attention to the dangers of personal use of these drugs without consulting a medical facility on its website and through the media. At the same time, we have decided to take the following measures to ensure that the drug is not imported and used easily by individuals:
1 Alert through the Ministry of Health, Labor and Welfare's website
(1) The Ministry of Health, Labor and Welfare (MHLW) has decided to post a Q&A on its website to widely urge people to avoid taking oral abortion pills without consulting a medical facility, as it is dangerous to do so.
(2) We have requested cooperation from the Japan Medical Association and other related organizations in order to understand the current state of health hazards and to promote alert measures. (Reference)

2 Strengthening of Monitoring and Guidance for Personal Import Agents
　Even if a company claims to be a personal import agent, there is a risk that it may be in violation of the Pharmaceutical Affairs Law, depending on the form of the advertisement, for example, by soliciting the wishes of an unspecified large number of people.

(1) Request each prefectural government to thoroughly monitor and provide guidance on the Internet advertising of personal import agents.
(2) Send warning e-mails to personal import agents and providers that advertise on the Internet.

3 Restrictions on Personal Importation
　The handling of oral abortion pills, which previously could be imported by individuals in small quantities without procedures at the Ministry of Health, Labor and Welfare, has been changed. From now on, the MHLW has decided to restrict personal importation so that, in principle, importation will be possible only when the local health and welfare bureau has confirmed that it is based on a doctor's prescription.

(Reference) Product names and other information on oral abortion pills for which personal importation is restricted and for which attention should be paid
　　Generic name: Mifepristone
　　Trade name:
(EU) Mifedine (Mifegyne)
(US) Mifeprex (Mifeprex)
(China) See-In
(Taiwan) Apano (added in May 2008)
Also known as "RU486" at the time of development.

Q&A regarding the oral abortion pill "RU486" or "Mifepristone Tablets

Q1. What kind of drug is "RU486" or "Mifepristone (mifepri- stone)", which is considered an oral abortion drug? Are they approved in Japan?
A1. RU486 or Mifepristone is an abortion pill that stops the action of the hormone progesterone, which is necessary for a pregnancy to continue.
　It is an unapproved drug in Japan, and its transfer and sale are prohibited by the Pharmaceutical Affairs Law.
　The active ingredient "Mifepristone" is approved in Europe and the United States as a drug that can terminate a pregnancy within 49 days of conception (from the start of the last menstrual period) when used with other drugs that cause uterine contractions, and a physician is required to use it and monitor its progress.

Q2. How is "Mifepristone" regulated in the U.S. and Europe? Can I import it by myself?
A2. In Europe and the United States, Mifepristone is a drug that can only be prescribed by a physician. The possibility of vaginal bleeding, serious infections, etc. is known, and it is necessary for a physician to monitor the patient after administration and to be able to visit a medical institution in case of an emergency. Even in Europe and the United States, the drug cannot be purchased at pharmacies without a doctor's prescription. It is also not allowed to be sold through the Internet.
　In addition, because the drug is ineffective against tubal pregnancies (ectopic pregnancies) and there is a risk of tubal rupture if it is not noticed and appropriate measures are not taken, a warning has been issued to medical institutions in the United States.
For these reasons, it is dangerous to obtain this drug through a private import agent on the Internet and use it for personal use, so please do not do so.

Q3. In what cases is Mifepristone prohibited in foreign countries?
A3. Mifepristone is not indicated for use in cases where it has been taken for more than 49 days since the beginning of the last menstrual period. In addition, the following patients should not take the drug

　- Tubal pregnancy (ectopic pregnancy)
　- Intrauterine device (IUD) users
　- Patients with adrenal gland disorders
　- Patients receiving steroid medication
　- Patients with abnormal bleeding or on anticoagulants
　- Allergic reactions to Mifepristone, Misoprostol, or similar medications.

Q4: What are the possible side effects or health hazards associated with Mifepristone?
A4. According to the foreign package insert, Mifepristone can cause vaginal bleeding. Occasionally, vaginal bleeding can be very heavy and in some cases requires surgical intervention to stop the bleeding.
　In addition, in November 2004, the United States added to the warning section of the package insert the possibility of serious bacterial infections such as sepsis and rupture of the fallopian tubes when administered to patients with ectopic pregnancies.
　Other known side effects include diarrhea, nausea, headache, dizziness, and lumbar back pain.

(Reference) Brand name and other information on oral abortion pills for which personal importation is restricted and for which attention should be paid
　　Generic name: Mifepristone
　　Trade name: Mifepristone (EU) Mifepristone (EU) Mifedine (EU)
(EU) Mifedine (Mifegyne)
(US) Mifeprex (Mifeprex)
(China) See-In
(Taiwan) Apano (added in May 2008)
Also known as "RU486" at the time of development.

MHLW of Japan: Important Points to Keep in Mind When Using Mifepristone and Misoprostol Products (Request)

The notice issued by the Ministry of Health, Labour and Welfare on April 28, 2023 on the newly approved oral abortion drug, Mefeego Pack

Important Points to Keep in Mind When Using Mifepristone and Misoprostol Products (Request)

To the Director-General of the Health Management Department (Bureau) of each prefecture, city with public health centers, and special ward

From the Director, Drug Evaluation and Control Division, Pharmaceuticals and Consumer Health Bureau, Ministry of Health, Labour and Welfare and the Director, Maternal and Child Health Division, Child Health and Welfare Bureau, Child and Family Affairs Agency

　We would like to thank you for your understanding and cooperation in the Ministry of the Health, Labour and Welfare and the Administration for Children and Families.
　We would like to inform you of the following matters concerning the use of Mifepristone and Misoprostol (trade name: Mefeego Pack) (hereinafter referred to as "the Drugs"). Mifepristone and Misoprostol (trade name: MephigoPac) were approved today for the indication of “abortion for confirmed intrauterine pregnancy of 63 days (9 weeks and 0 days) or less of gestation”. In Japan, only designated doctors under the Maternal Body Protection Law (Act No. 156 of 1948) are allowed to perform abortions, and the use of this product is treated in the same way. We would therefore like to ask you to take the following points into consideration when using the drug. We would like to add that we have separately requested the same information to the President of the Japan Medical Association.

　The details of the request are as follows:

1. The administration of the drug (oral administration of Mifepristone and buccal administration of Misoprostol) must be performed under the confirmation of a designated doctor under the Maternal Body Protection Law.

2. The package insert states that the designated doctor under the Maternal Body Protection Law should administer the drug under a system that can take appropriate actions in an emergency (a system for receiving constant contact from the person who received the drug in case of any abnormality and an emergency system that includes cooperation with other medical institutions).
However, until an appropriate system for the drug use is established, the drug should be used in a hospital or clinic where patients can be admitted for the time being. After the administration of Misoprostol, patients must be hospitalized or remain in the medical institution until the fetal sac is discharged. In this case, "for the time being, until an appropriate system for use is established" will be reviewed and judged based on the results of a sufficient amount of research to be conducted after approval, in which an appropriate medical coordination system will be evaluated.

3. The approval of this product is subject to the condition that "necessary measures shall be taken to ensure that this product is used only by designated doctors under the Maternal Body Protection Law, including the implementation of distribution management in cooperation with related organizations, etc." In the Distribution Management Procedures, etc., each prefectural medical association is required to receive monthly reports from drug manufacturers, distributors, and medical institutions on sales volume, usage volume, and other necessary matters, respectively. Each prefectural medical association shall provide necessary supervision and guidance to designated doctors under the Maternal Body Protection Law by checking the consistency of these reports as appropriate. In doing so, it is acceptable to tailor the operation to the actual conditions of each region.

4. Although dead fetuses under 4 months of pregnancy are not subject to the Graveyards and Burials Act (1948 Law No. 48), we request that they be handled appropriately at each medical institution, while giving consideration to the feelings of women who have experienced an abortion.

5. If a designated doctor under the Maternal Body Protection Law uses this drug in a medically appropriate manner, a series of abortions with this drug falls under the definition of "abortion" in Article 2.2 of the Maternal Body Protection Law, and if the discharge of the gestational sac is observed before the administration of Misoprostol and the designated doctor under the Maternal Body Protection Law determines not to administer the Misoprostol, it can be interpreted that an abortion is being performed under the Maternal Body Protection Law.

MHLW of Japan：Proper Use of the So-Called Oral Abortion Drug “Mefeego Pack”

The announcement made by the Ministry of Health, Labour and Welfare of Japan on April 28, 2023 for the newly approved abortion drug, Mefeego Pack

Proper Use of the So-Called Oral Abortion Drug “Mefeego Pack”

　Since only designated doctors under the Maternal Body Protection Law are allowed to use the so-called oral abortion drug "Mefeego Pack" and strict administration of the drug is required, we will provide some points to keep in mind so that the drug is used properly.

Outline of Mefeego Pack
Trade name: Mefeego Pack
Generic name: Mifepristone/Misoprostol
Approved to: Linepharma K.K.
Abortion for patients with a confirmed intrauterine pregnancy of 63 days (9 weeks and 0 day of gestation) or less
Dosage and Administration One Mifepristone tablet (200 mg as Mifepristone) is administered orally, and 36 to 48 hours later, depending on the condition of the patient, 4 Misoprostol buccal tablets (total 800 μg as Misoprostol) are placed between the gums and cheeks of the right and left molars, 2 tablets each for 30 minutes. 30 minutes after placement If any Misoprostol tablets remain in the oral cavity, swallow them. Abortion can only be performed at a medical institution with a designated Maternal Body Protection Law doctor.
　It cannot be purchased at pharmacies or over the Internet.
Efficacy and Safety
1 Efficacy
　In a domestic Phase III study, the percentage of subjects who had a successful abortion by 24 hours after receiving Misoprostol, which was considered the primary endpoint, was 93.3% (112/120 subjects).

2 Safety
　The incidence of adverse events in the domestic Phase III study was 57.5% (69/120 subjects), with the most common adverse events being lower abdominal pain (30.0%) and vomiting (20.8%). Serious adverse events reported included severe uterine bleeding (0.8%) and infection (frequency unknown).

Important Points to Consider in the Use of Mefeego Pack
　In the "Precautions in the Use of Mifepristone and Misoprostol Products[attached at the bottom of this document] (Ministry of Health, Labour and Welfare, Pharmaceutical and Welfare Bureau, Drug Evaluation and Administration Division Director and Child and Family Health Division Director jointly issued a notice on April 28, 2023, No. 0428-5 and No. 54)”, the following precautions are indicated for the use of Mefeego Pack. The main contents of the notice are as follows:

1. The drug should be administered under the confirmation of a designated doctor under the Maternal Body Protection Law.

2. For the time being, the drug should be used in a hospital or clinic where patients can be hospitalized until an appropriate system for its use is established.
　Misoprostol should be used only in a hospital or clinic where patients can be admitted for the time being until the appropriate system for its use is established. After the administration of Misoprostol, patients must be hospitalized or must remain in the hospital until the fetal sac has been expelled.
　The "appropriate system of use" should be defined as follows. The "for the time being, until an appropriate system for use is established" is subject to the implementation of sufficient research and studies after approval and the development of appropriate medical care coordination within that system.
　The "appropriate medical coordination system for the time being until the appropriate system for use is established" shall be fully investigated and studied after approval, and the appropriate medical coordination system shall be evaluated in the course of the investigation and study.

3. Each Prefectural Medical Association shall provide necessary supervision and guidance to designated doctors under the Maternal Body Protection Law by receiving monthly reports from drug manufacturers, distributors, and medical institutions, respectively, and checking the consistency of such reports as appropriate.

To those who wish to receive Mefeego Pack
　The administration of Mefeego Pack is possible only after the physician has provided sufficient explanation of the risks and efficacy of the drug, as well as necessary measures, in accordance with the package insert and other relevant documents, and when consent has been obtained.

　The main points to be noted are as follows:

Mefeego Pack is not prescribed through online medical services. It is necessary to visit a medical institution.
The drug may cause lower abdominal pain. If abnormal pain persists, the patient should promptly receive a prescription for The drug at a medical institution, as there is a possibility of simultaneous intrauterine and extrauterine pregnancies.
　If the pain persists, contact the prescribing healthcare facility immediately.
In rare cases, severe uterine bleeding may occur after the drug administration. Basically, bleeding that requires changing a nighttime sanitary napkin more than twice an hour should be reported.
If bleeding continues for more than 2 hours, which requires changing a nighttime sanitary napkin more than twice an hour, contact the prescribing health care provider as soon as possible.
Since uterine bleeding with syncope may occur, extreme caution is required when operating potentially hazardous machinery such as driving a car.
Even after a certain period has passed after the administration of this drug, infections such as endometritis may occur, and fatal episodes of infection such as sepsis have been reported.
　If symptoms of infection such as fever, chills, fatigue, abnormal vaginal discharge, etc. are observed, contact the medical institution that prescribed the drug as soon as possible.
If an abortion using Mefeego Pack is not completed, surgical treatment may be considered.
In the case of an abortion with Mefeego Pack, uterine contents may remain even after the gestational sac has been expelled. In such cases, however, surgery to remove the uterine contents is not always necessary.
If you have an IUD or IUS, the IUD or IUS should be removed prior to administration of this product due to the risk of ineffectiveness or uterine damage.

Contact for Consultation
In addition to the prescribing medical institution, the following counseling services are also available.
■PMDA (Pharmaceuticals and Medical Devices Agency) Pharmaceuticals Consultation Service
The PMDA provides consultation services on the efficacy and effectiveness of drugs, drug combinations, how to take and use drugs, and other concerns related to drugs.

Telephone number: 03-3506-9457

Office hours: Weekdays from 9:00 a.m. to 5:00 p.m.
(Closed on Saturdays, Sundays, national holidays, and year-end and New Year holidays.

Consultation Service for Patients and the Public | Pharmaceuticals and Medical Devices Agency (pmda.go.jp)
https://www.pmda.go.jp/safety/consultation-for-patients/0001.html

■System for Relief from Adverse Reactions to Drugs
This is a public system that provides benefits such as medical expenses and pensions if a patient is hospitalized or becomes disabled after suffering serious side effects from the correct use of medicines provided at a hospital or clinic or purchased at a pharmacy. For details of the system, please contact PMDA.

Phone number: 0120-149-931

Reception hours: Weekdays from 9:00 a.m. to 5:00 p.m.
(Closed on Saturdays, Sundays, national holidays, and year-end and New Year holidays.

Adverse Drug Reactions Relief System (pmda.go.jp)
https://www.pmda.go.jp/kenkouhigai_camp/

■Smart Health Consultation Office
This is a health consultation support site for young people regarding sex, pregnancy, etc.

Smart Health Consultation Room - Health Consultation Support Site for Young People's Sexuality and Pregnancy (mhlw.go.jp)
https://youth.mhlw.go.jp/

Mefeego Pack approved as 1st abortion pill in Japan

The Mainichi April 28, 2023 (Mainichi Japan)

Mefeego Pack approved as 1st abortion pill in Japan - The Mainichi

TOKYO (Kyodo) -- Japan's health ministry approved Friday for the first time the sale of an oral abortion pill, giving women in early pregnancy an alternative to the surgical procedure.

The pill, called Mefeego Pack developed by British pharmaceutical company Linepharma International Ltd., can terminate a pregnancy of up to 9 weeks of gestation, and is considered safer than the surgical abortions that have been used hereto.

Mefeego is a two-drug combination of mifepristone, which blocks a pregnancy hormone, and misoprostol, taken 36 to 48 hours later to stimulate uterine contractions.

Until now, only surgery was approved for early-term abortions, but the method of removing tissues with medical instruments was criticized as risking harming the uterus.

Because Mefeego's possible side effects include abdominal pain and bleeding, women who take the pill must stay in hospital until the abortion is confirmed by doctors.

To ensure the drug's thorough management, pharmaceutical companies and medical institutions are also asked to give monthly reports to their local medical associations on the number of pills that have been sold and used.

The World Health Organization includes the medication on the list of essential drugs for abortion, and has promoted the abortion pill as a safe alternative. Oral abortion pills are used world-wide, with France having approved them more than 30 years ago.

Mefeego Pack is available in 80 countries, according to Linepharma International.

The Ministry of Health, Labor and Welfare approved it under the country's maternal health law, whose purpose is to protect the lives and health of pregnant people related to induced abortions and sterilizations.

The nation's first abortion pill has elicited considerable interest, over greater choice for women, its possible side effects and price.

Mefeego's manufacturing and marketing was approved by a health ministry panel last week after the ministry received around 12,000 public comments.

There were 126,174 abortions in Japan in fiscal 2021, according to the health ministry.

Japan panel approves nation's first abortion pill

Japan Times BY KATHLEEN BENOZA, Apr 21, 2023

www.japantimes.co.jp

My comments are scattered in the article:

……
Kumi Tsukahara, director of the Reproductive Health Rights Literacy Institute, said the decision was positive in terms of putting a spotlight on these issues, but she cautioned that the drug could be inaccessible to some.

On Friday, the Pharmaceutical Affairs Council discussed whether to approve manufacturing and sales of the drug. The pill pack, to be administered at medical institutions, includes two types of drugs, mifepristone and misoprostol, and is intended to be taken orally within the first nine weeks of pregnancy.

The government will also work to create guidelines for physicians and offer the public information on the drug.
Tsukahara says the government should establish a separate system to train medical practitioners on ways to communicate about abortion without stigma as well as to assess the risks.

“It’s important that they help patients understand what is safe and what is not, enabling them to make their own decision,” Tsukahara said.

Friday’s decision comes after an initial advisory panel at the health ministry approved the production and sale of the drug in January. In early April, the health ministry said it was considering plans to make it mandatory for patients to wait for up to a day at hospitals until the abortion is confirmed, after the administration of the second pill.

This also applies to outpatients, with the decision expected to be in effect for an indefinite period after approval for the pill pack.

In clinical trials, 60% of medical abortions using the Mefeego pill pack were confirmed at four hours after the second dose, with the figure reaching 90% after eight hours. In less than 10% of cases, abortion was
unsuccessful even after 24 hours.

Currently, surgical procedures, allowed at the early stages of pregnancy, are the only options available for an abortion in Japan, despite the World Health Organization having endorsed the pill as one of the safest methods.

The approval of the pill in Japan would mark progress for women’s reproductive rights, but debates over pricing and consent have cast a shadow over the decision.

Mefeego will not be covered by Japan’s national health insurance, andwith women being required to take the drugs under medical supervision, costs may be greater than if one were to get a surgical abortion, even if the average wholesale price of abortion pills globally is estimated to be around ¥780 to ¥1,400.

Surgical procedures for abortion in Japan cost ¥100,000 to ¥200,000 (around $730 to $1,500).
The cost of the drug could make it inaccessible for some, but its approval can be seen as a first step, Tsukuhara said.

Another factor is Japan’s Maternal Health Act, which requires spousal consent for an abortion — a policy that prevents access in some cases.

The health ministry says the law will be applicable to abortion pills.
Exceptions to the consent policy are granted for situations where the spouse is unknown or is unable to express intention.
While a partner’s consent is not legally needed for unmarried women, many doctors require a man’s consent due to a lack of understanding and fear of legal consequences.
The law includes no provision for unmarried mothers. However, the health ministry has said a partner’s consent is not required for unmarried women or those impregnated through rape.

Such cases have led to tragic incidents, such as when a 21-year-old former nursing school student was handed a suspended prison sentence for abandoning her newborn in a public restroom at a park.

In court, the woman said the hospital required male consent, which she was unable to acquire, highlighting the limitations to reproductive rights in Japan.

“Being able to control one’s own pregnancy is already the minimum requirement for gender equality,” said Tsukahara. “Although this discussion is on medicine, we must not lose sight of how this is a human rights issue.”

NHK NEWS WEB reported on approval of Japan’s first oral abortion pills

NHK NEWS WEB reported on approval of Japan’s first oral abortion pills

“Oral Abortion Pill" Health Ministry Subcommittee Approves Japan's First Approval.
April 21, 2023 9:45 pm

A subcommittee of experts from the Ministry of Health, Labor, and Welfare (MHLW) has approved the first approval in Japan for "oral abortion pills," which are used to perform artificial abortions with medication.
The MHLW is expected to officially approve the drug in the near future.

The drug is named Mefeego Pack, developed by the British pharmaceutical company Linepharma.
The drug is intended to stop the continuation of pregnancy by taking two types of medication in sequence, enable to perform an abortion without surgery or other surgical procedures.
Pregnant women up to 9 weeks gestation are eligible for this procedure.

In January of this year, a panel of experts from the Ministry of Health, Labor and Welfare agreed to approve the procedure, but decided to discuss it again at an upper-level subcommittee meeting, citing the need for careful discussion.
At the panel meeting on January 21, it was agreed to approve the use of the drug on the premise that it should be handled with caution.

Specifically, only doctors designated by prefectural medical associations as "Maternal Body Protection Law designated doctors" will be allowed to administer the drug, and its use will be permitted only in hospitals and clinics that have beds in case a person who has taken the drug lies down.

In addition, while both inpatient and outpatient use is allowed, for the time being, until a system for use is established, patients must remain in the hospital until the abortion is confirmed.

Furthermore, strict standards will be set for the management of the drug, with manufacturers and medical institutions required to report monthly to prefectural medical associations on the number sold and the number used.

In a domestic clinical trial using the drug, 93% of pregnant women seeking an abortion completed the procedure within 24 hours, and although approximately 60% complained of abdominal pain and other symptoms, most of the symptoms were mild or moderate.

The Ministry of Health, Labor, and Welfare is expected to formally approve the procedure, which will make it possible to perform abortions with the drug.

Doctors who have sought approval "expect the operation to be based on international recommendations"
Dr. Sakiko Enmi, an obstetrician and gynecologist and representative of a citizens' group that has been seeking approval for oral abortion pills, said, "The approval comes after more than 30 years of delay, but if there are factors that hinder access, such as high costs and uniform hospitalization management, it will eventually be difficult for patients to access the pills and make it difficult for them to use them. There is also concern that this may end up making it difficult for people to reach and use the drugs. We hope that the system will be operated based on international recommendations and scientific evidence," he said.

She continued, "In Japan, there are many issues, not only abortion methods, but also the high cost, laws requiring spousal consent, and discrimination and prejudice that arise from a false understanding of the issue. I hope that many people will think about safe abortion.

Dr. Ishiwata, President of the Japan Association of Obstetricians and Gynecologists: "It is important to provide accurate explanations”
Isamu Ishiwata, President of the Japan Association of Obstetricians and Gynecologists, said, "I welcome the increase in the use of abortion pills as an alternative to surgery. Looking at the situation overseas, the ratio of abortion pills to surgery is expected to eventually reach about 50-50 in the future. While the availability of medication is considered useful in the case of those who are at risk for anesthesia or surgery, approximately 10% of the patients do not expel spontaneously and require additional surgery or other procedures. It is important to accurately explain the advantages and disadvantages of both abortion pills and surgery," he said.

He added, "We would like to promote correct knowledge of the drugs before they are actually used in the future. To prevent inappropriate use, the government is trying to establish a strict management system, and the medical association is also considering rules for punishing doctors who use the drug inappropriately.

What are oral abortion pills?
Oral abortion pills are two types of pills that are taken to perform artificial abortions. After conducting clinical trials in Japan, the British pharmaceutical company Linepharma applied to the Ministry of Health, Labor and Welfare for approval.

Pregnant women up to 9 weeks' gestation are eligible for the procedure, which involves taking a drug called "Mifepristone," which suppresses hormones to stop the progress of pregnancy, followed 36 to 48 hours later by a drug called "Misoprostol," which causes the uterus to contract.
Together, the two drugs are marketed as "Mefeego Pack.

Unlike surgery, which has been the only option, oral abortion pills do not require anesthesia and have a low risk of damaging the uterus.

Efficacy
In a clinical trial conducted in Japan, of 120 pregnant women who requested an abortion, 112, or approximately 93%, completed the procedure within 24 hours, but five were unable to expel the pregnancy and three had to be removed because parts remained inside their bodies.

Safety and side effects
In the clinical trial, 69 patients (approximately 58%) complained of symptoms such as abdominal pain and vomiting after taking the drug. Four of these patients had severe symptoms such as abnormal uterine bleeding and endometritis, but most had mild or moderate symptoms.

Cost
As abortion is, in principle, a free medical procedure not covered by public insurance, the cost of medical abortion is determined by each medical institution.
According to the Japan Association of Obstetricians and Gynecologists, "The price of the medication is estimated to be about 50,000 yen, and when combined with the consultation fee, the cost is expected to be about 100,000 yen.

The situation of its widespread use in other countries is unknown
The World Health Organization (WHO) has designated this oral abortion pill as an "essential drug" because it is safe and effective.
According to the Pharmaceuticals and Medical Devices Agency (PMDA), which is in charge of drug screening, Mifepristone, a drug that suppresses the function of hormones to stop the progression of pregnancy, was first approved in France in 1988 and was approved in more than 65 countries and regions as of September last year,
Misoprostol, which causes the uterus to contract, is approved in more than 93 countries and regions.
In France, the UK, and other countries, they are also being prescribed for online medical treatment.

Abortion methods in Japan
In Japan, the only abortion methods have been surgical procedures, either the sobriety method, in which a metal instrument is inserted into the uterus and scraped out, or the suction method, in which a soft plastic tube is attached and sucked out manually, or a combination of the two is used.

According to a nationwide survey conducted by the Japan Association of Obstetricians and Gynecologists, as of 2019, the number of abortions performed using both the "soha-ho*1" and "suction" methods was the largest, at about 40% of all abortions, with the "suction" method accounting for about 36% and the "soha-ho" method for about 24%.

The WHO recommends the use of drugs and aspiration methods.<<<<<<<<<<<<<<<<<<<<<<<<<<<<<

Translated from the original in Japanese by Kumi Tsukahara.

*1:D&C after using forceps