|RU486 : A DANGEROUS PRODUCT|
Dangerous for the children, of course, and also for the mothers.
The scientifique report of the International Inquiry Commission on RU486, dated April 1990, already established it, one year before the first known death due to RU486. This report precisely explains what is actually RU486:
REPORT OF THE INTERNATIONAL
INQUIRY COMMISSION ON RU 486
BP 167 - 92805 PUTEAUX - FRANCE April 1990
Scientific and Medical committee:
Pr André DELMAS, president of the National Academy of Medicine
Pr Bernard ANTOINE, head of the service of Nephrology (Necker Hospital, Paris)
Pierrette CHATEAU-RAYNAUD, research director in CNRS
Pr André CORNET, Academy of medicine
Bernard KERDELHUÉ, research director in CNRS, commission INSERM of Endocrinology
Pr Pierre MAGNIN, Pharmacology, Academy honorary rector, head of a service in the hospital CHU Besançon
Pr Michel PIERSON, head of the service of Medical Genetics (hospital CHU Nancy)
Pr J.P. RELIER, head of the service of Neonatal Medicine (hospital Cochin, Paris)
Serge RENAUD, research director in INSERM
Pr Pierre de VERNEJOUL, commission of Pharmacology and experimental Therapeutics of the CNRS
On December 28, 1988, the Health Minister, Mr ÉVIN, issued the A.M.M. (Autorisation de mise sur le marché = permission to be released on the market) for the molecule ROUSSEL-UCLAF # 486 (also called MIFEPRISTON) associated with prostaglandins, indicating that it is the "medicinal" alternative for a surgical termination of pregnancy (I.V.G.), calling for several major objections from us.
1) Was a commission normally constituted to express opinions prior to granting of the A.M.M. by the Minister, the only competent body for voicing an opinion on RU 486, that has nothing in common with a medicine, knowing its targeted function?
Wasn't it also necessary, taking into account the biomedical and scientific importance of the problem, to extend this commission? To that end, given the potentially dangerous absence of analogical references for this compound, it would have been prudent to consult the obstetrician-gynecologist corporation, and the competent authorities of the INSERM (National Institute for Health and Medical Research), as well as those of the CNRS (National Center for Scientific Research) National Committee?
Furthermore, the recommendations of the National Committee of Ethics and the Helsinki International Convention were not respected.
Besides, the studies on non-therapeutic abortion carried out in France were not all in strict accordance with the Veil law of 1975: certain abortions were performed outside the orthogenics centers provided for this purpose.
2) On the medical scientific level, it was first of all proven and largely confirmed that this molecule is a very strong anti-glucocorticoid. Only later the anti-progesteron activity was discovered.
It is none the less regrettable that the decision-makers of Roussel-Uclaf have not chosen to develop a molecule in which the anti-glucocorticoid activity would have been negligible with regard to the anti progesteron activity.
Even though no accident due to this effect have been reported to this day, (maybe due to the fact that RU 486 strongly stimulates and for a long time the production of ACTH and of cortisol through a discontinuance of the homeostasis of the corticotrop axis), an accident would always be possible for a woman with insufficient suprarenals, and could be made obvious through a large sample of patients treated with RU 486.
This is an unhappily classical fact in clinical toxicology: relatively minor incidents are discovered through middle series (from 1,000 to 10,000 cases), but a severe accident happens in more important series (from 20,000 to 50,000 cases).
Moreover, it seems necessary to inject a high quantity of the product (1,000 times the normal quantity used for steroids), the effect seems not proportional to the quantity administered, and the product seems to have a long plasmatic half-life.
3) Contrary to the allegation that the understanding of its action mechanism led to the selection of this product, it remains obvious that the action mechanism(s) of RU 486, which leads to the elimination of the fetus, are far from being clear. In brief, the molecule does not function except in the presence of a sufficient concentration of progesteron and, furthermore as in the case of the corticotrop axis, RU 486 disturbs the function of the gonadotrop axis, in animals as well as in man.
A publication issued by the Bygdeman Laboratory (Contraception, 29, 1984, pp. 399-409), concluded by saying that the efficiency of taking RU 486 needed to be improved to be able to compete with the suction method, because of the high frequency level of failure. The results obtained since that time on a large scale, have shown the failure percentage to be around 40 %.
For this reason, this same laboratory having done previously studies on the luteolytic effects of the sole use of prostaglandins for abortion, proposed a research putting RU 486 primarily in the forefront, followed by prostaglandins. This treatment resulted resulted in a success rate superior to 90 %, but on the other hand, with the prostaglandins known side effects:
- important digestive troubles, diarrhea, nausea and vomiting,
- violent uterine pain, painful like a birth,
- cardiovascular and respiratory risks.
Besides, the side effects of the association of RU 486 with prostaglandins are not known.
4) The major side effect observed up to date remains the uterine metrorrhagia which develops in more than 90 % of the cases, after administration of RU 486, and can last up to more than one week (from 1 to 35 days). In many cases an emergency "Révision Utérine" was necessary to contain the hemorrhaging. In certain cases, the only recourse was an emergency blood transfusion, with all the risks this involves.
Moreover, in many cases, apart from any success or failure in the abortion, a drop (from 1 to 6 g/dl) in the level of haemoglobin, associated with an average drop of 30 % in haematocrite was observed and led to a methylergometrin, iron or vitamin therapy treatment.
Could these drops in haematological constants explain the few coronarite cases recently observed after taking prostaglandins (cases implying an appropriate cardiologic follow-up)?
This cardiologic follow-up, only recently demanded, was imperatively claimed in the VIDAL, wherein is written, for the use of NALADOR, (Sulproston, one of the synthetic by-products of prostaglandin E2 ; used with the RU 486), it is necessary:
- to administer under constant medical supervision (in a gyneco-obstetrics service with reanimation and "monitoring" equipment to deal quickly with a possible accident),
- to imperatively frequently inspect the circulatory and respiratory functions.
Was a negligence to observe these imperative directions accountable for the 36 hours long coma, recently noticed during a "medicinal" pregnancy termination?
5) Presently the experts seem to be in agreement in recognizing that adding prostaglandins to RU 486 converts the try put by RU 486. Besides, the pre-treatment by RU 486 permits to diminish the abortive dose of prostaglandins. It is therefore incorrect to say that the abortive effect is provoked by RU 486 since, administered alone, it works in only 60 % of the cases. Moreover, this last figure varies a lot (+/-20 %), for unexplained reasons, from one experimental center to another. They speak of an "apprenticeship effect" from the experimenter...
6) Under these conditions, where is then the "authentic medicinal" alternative to a surgical termination? Beyond far heavier risks than by the surgical method (in which all is finished in 6 hours with little complications at 7 weeks amenorrhea) there is - with the medicinal method - an uncertainty about the result during 5 to 12 days.
This is the schedule for a termination with RU 486 + prostaglandins:
- consulting for the taking of the pills,
- ordering to a hospital during 12 hours the next day for the prostaglandins injection,
- expelling in 80 % of the cases this same day or the next night,
- new prostaglandins shot for the remaining 20 %,
- failure for 5 % of the women who will therefore undergo surgery,
- around 5 to 10 % persistent hemorrhages will need medicinal or surgical treatment,
- absolute necessity, some days after abortion, to practice an ultrasound examination and a HCG dosage, to be completely sure there is no traces of the fetus.
In any case, she has to undergo a surgical termination if the RU 486 does not function as an abortive.
As a matter of fact, we actually have no data at our disposal on the fetotoxity of the molecule in the human race. This urgent recommendation ensues from a work by A. JOST (C.R. Acad. Sc. Paris, Ser.III, 303, 1986, pp. 281-284) in which RU 486 was administered to pregnant rabbits and where severe teratological fetal anomalies were observed in full-term fetuses.
In addition, we know, since a long time, that prostaglandins have teratological effects as much on animals (Teratological testing, 2, 1979, pp. 161, 177) as on men (J. Pediatr., 102, 1983, pp. 620-621).
These points should be clearly explained to the women desiring to use this method.
7) What then must be the attitude of the prescriber if the pregnant woman having taken RU 486 does not come to take the prostaglandins, without which RU 486 is not sufficiently effective? What to do about those "disappeared out of sight" between two "treatments"?
8) We are also told that RU 486 could be a therapeutic agent in the treatment of breast cancer, neuro-psychiatric troubles, "stress" and... difficult birth. Where are the experimental proofs?
In fact, a work recently published in a well-known international scientific magazine, proved the contrary, i.e. a strong stimulating effect by RU 486 on the growth of a breast cancerous cellular line (line T 47D) (Endocrinology, 124, 1989, pp.2642-2644).
It must also be remembered that this symptoms need long-term treatment which is not reconcilable with the anti-glucocorticoid activity of the product, and, interestingly with its inhibitory properties on the immunitory system (J. Clin. Endocrinol. Metab., 69, 1989, pp. 1195-1199).
9) On the Social Security budget level, it is astonishing to see this new "treatment" justified as a desirable alternative to suction abortion, because it needs a far more constraining supervision:
- increasing the number of mandatory visits,
- more complex investigation tools (recently the electrocardiogram has been added to an already long and expensive list).
Will the price set in the "Journal Officiel" (FFR 1407.65) be sufficient to cover the costs of the imperatively prescribed extra examinations due to this technique?
Moreover, on an economic level, no "return on investment" can be waited for, because this "targeted" risk "market" cannot be dealt with, in any way, by the pharmaceutical industry professionals.
10) Is it therefore very reasonable an worthy of the French Medicine, which has been, and which still is, outstanding in numerous fields, to want to impose on France, and in particular to export to Third-World countries which, unlike us, do not have the medical high technology necessary to keep a watch on these abortions, a technique which is very painful and difficult to handle?
©TDD - reproduced with authorization