Mifepristone (RU 486)

1. Mifepristone (RU 486) How it works and what it does Assoc Professor Anne Tonkin, Clinical Pharmacologist,University of Adelaide and Royal Adelaide Hospital Former member, Australian Drug Evaluation Committee and Pharmaceutical Benefits Advisory Committee

2. How it works (1) • In exactly the same way as dozens of other drugs • Prevents the action of a body “messenger” (in this case, a hormone) • Similar approach for drugs used for heart disease, high blood pressure, etc etc • NOT a toxin or poison; causes no direct harm

3. How it works (2) • Control of many body functions uses “lock and key” approach • Hormones (“keys”) act only in parts of the body where the right shaped receptors (“locks”) are present Hormone This key does not fit this lock Key fits this lock and opens it

4. How it works (3) • Many drugs are “false keys” – fit the lock but will not turn it • true key can’t reach lock • “receptor antagonists / blockers” “True key” cannot reach lock Hormone Drug “False key” fits but lock does not open

5. How it works (3) • Many drugs are “false keys” – fit the lock but will not turn it • true key can’t reach lock • “receptor antagonists / blockers” Hormone can’t reach receptor Hormone Drug Drug (“false key”) fits but receptor is not activated No hormone effect

6. How it works (4) • Mifepristone blocks progesterone receptors • prevents normal effects of progesterone on uterus (needed to maintain early pregnancy) • effect is similar to insufficient production of progesterone (causing natural miscarriage) • also reduces stimulatory effect of progesterone on endometriosis, tumour growth, etc

7. What it does (1) • Prevents progesterone from having its usual effects in early pregnancy • pregnancy can no longer be maintained and is miscarried (very similar to natural miscarriage) • side effects are very similar to complications of natural miscarriage • about 95% can avoid anaesthesia/operation • side effects of the drug itself are minimal (absence of progesterone effect causes few if any symptoms) • fatigue, loss of appetite, nausea in a few

8. What it does (2) • Other uses demonstrated in clinical trials: • Contraception • Endometriosis • Breast cancer • Meningiomas (benign brain tumours) • Uterine tumours (benign and malignant) • Alzheimer’s disease • Stigmatization as an “abortion drug” has inhibited research on some of these uses • May have been a different debate if treatment of fibroids had been developed first?

9. Drug regulation: Benefits vs risks • Drug regulatory system is specifically designed to assess benefit:risk balance • Other drugs involved in the process of medical termination • have other well-established uses such as gastric ulcer prevention (misoprostol) or arthritis (methotrexate) • these are regulated in the usual TGA system • Mifepristone has several potential uses in addition to termination of pregnancy, all of which should be assessed by the TGA system

10. Benefits vs risks • Methods of non-surgical abortion • most effective is combination of mifepristone and a prostaglandin drug • less effective alternative is methotrexate and a prostaglandin (both available in Australia) • Mifepristone combination method is used widely around the world • UK since 1991, Sweden since 1992, USA • studies on women’s preferences consistently favour medical over surgical abortion

11. Main messages • Mifepristone is a drug like any other • Blocks progesterone receptors • Has a variety of established and potential uses apart from non-surgical abortion • Other drugs used for non-surgical abortion are regulated in the usual TGA system and available in Australia • There is no scientific or medical reason for continuing the special arrangements for mifepristone