Ivar Brod, Pan Am Pharmaceuticals, Inc., New York, USA
Christian Fiala MD, Gynmed Ambulatorium, Vienna, Austria
Misoprostol has been widely used in Ob/Gyn practice since the early days of its appearance on the market. However, Pfizer, the current manufacturer, so far has rejected continuous requests to add these indications. Moreover, in countries like Estonia and Latvia where registration expired, manufacturer refused to prolong it. We believe that the company’s reasons were financial only, since the price of Misoprostol is more than 10 times lower than the price of other prostaglandins, injectable or jelly, produced by this company. This reason overweighs the fact that other prostaglandins (E2 and F2a analogs) can cause heavy adverse effects, like myocardial infarction and bronchospasm, which is not the case for Misoprostol (E1 analog).
The use of Misoprostol in Ob/Gin in USA is based on FDA’s general recognition that off-label use of approved medicine is acceptable, if it’s based on published scientific evidence. Similar recommendations have been accepted by the European Community Pharmaceutical Directive as well as by British National Formulary. There are no such policies in countries of Eastern Europe - Russia and other post-communist countries. Data that is being analyzed is mainly from Russia, which is typical for all of these countries. Existing legislation there does not provide any positive information about the off-label use of medicine. Moreover, in case of Misoprostol, medical authorities periodically issue directions prohibiting the access to it, due to the lack of indication by the manufacturer. The first of such Directive Letters was issued in April 1999 by Russian Ministry of Health forbidding the use of prostaglandins for off-label indications. The last Directive Letter as of July 2003 forbids directly the Ob/Gyn use of Misoprostol. The breach of these directives can be assumed as a criminal case.
One of the biggest problems for countries like Russia, where 60% of pregnant women prefer abortion and 15% of women in reproductive age are sterile, is to conduct a gentle abortion procedure in order to avoid any harm to female’s reproductive system. Many experts acknowledge that medical termination of pregnancy, using mifepristone followed by Misoprostol, is the most merciful abortion method. Mifegyne (mifepristone), known as the most excellent medicine for medical termination of pregnancy, has been registered in Russia in 1999. Ban of Misoprostol use significantly deprived Russian women the right to choose this method of medical abortion.
There is one more serious aspect resulted from Misoprostol ban in obstetrics in Russia. Help to pregnant women during childbirth is particularly important in this country where more than 10% of deliveries present with high risk of complications for mother and a baby. More than 1/3 of those caused by failure to progress in labor. Russian Ob/Gyn specialists found direct correlation between using Mifegyne and Misoprostol and raising the Bishop range from 0-3 to 4-7. As a result, this method was patented and these indications were formulated in the instruction. Misoprostol ban in obstetrics makes it impossible to use this remarkable mode.
The literature supporting Misoprostol Ob/Gyn use is rather vast – more then 400 publications in leading medical journals. Among them there are publications of experts in Russia, Ukraine, Latvia, Lithuania, and others. Moreover, in Russia in 2004 is published a spacious monograph devoted to Ob/Gyn use of Misoprostol. However, most of all reported brilliant results were based on the use of Misoprostol in research institutions, not in general practice.
We have to stress, that the situation with Misoprostol is special because it is officially recommended to be used in Ob/Gyn by World Health Organization issuing in May 2003 the guidance “Safe Abortion: Technical and Policy Guidance for Health Systems”. We believe that these recommendations allow us to call upon medical authorities in countries of Eastern Europe to acknowledge that Misoprostol was proven to be a prominent drug in Ob/Gyn and to define the way of its appropriate use. Women should not be held hostage by the economic considerations of a private pharmaceutical company in the United States.