1. Orawee Chinthakanan, MD, MPH
Medical abortion
Orawee Chinthakanan, MD, MPH

3. Overview Identify current medication abortion methods and present
Mechanisms of action
Regimens, efficacy, and safety
Eligibility requirements and contraindications
Side effects and complications
WHO guideline
Current study in Thailand

4. Medication Abortion Advantages 95-99% effective
Avoids surgical and anesthetic risk
Greater patient autonomy & privacy
Less invasive
More “natural”

5. Medication Abortion Regimens: Three Choices
Mifepristone + Misoprostol
Methotrexate + Misoprostol
Medical Abortion Regimens:
Mifepristone + misoprostol is the main regimen used currently in the US.
Mifepristone’s high cost limits its use in many countries – and for uninsured/underinsured women in the US.
This presentation focuses mainly on mifepristone/misoprostol abortion.
We will review the 2 other options briefly at the end.
Misoprostol alone

6. Medication abortion Methods of action of the medications
Mifepristone (RU-486)
Anti-progestin that blocks the action of progesterone
Alters the uteral lining
Methotrexate
Anti-metabolite
Interferes with DNA synthesis and cell growth
Misoprostol
Prostaglandin E1 analog
Stimulates uterine contractions and induces cervical softening

8. Medabon
Medabon® consists of two medicines: mifepristone and misoprostol.
The Medabon® regimen is in line with current (as of June 2009) WHO recommendations for medical abortion1: one 200-mg tablet of mifepristone given orally, followed 24–48 hours later by four 200-μg tablets of misoprostol. The four misoprostol tablets can be administered vaginally or sublingually.
Medabon® is registered for use in pregnancies through nine weeks (63 days) since a woman’s LMP.

9. Use of Mifepristone Worldwide
Millions of women have used mifepristone for medical abortion.
Year that mifepristone was licensed
France-1988
China-1988
UK-1991
Sweden-1992
Austria-1999
Belgium-1999
Denmark-1999
Finland-1999
Germany-1999
Greece-1999
Israel-1999
Luxembourg-1999
Netherlands-1999
Spain-1999
Switzerland-1999
Norway-2000
Russia-2000
Taiwan-2000
Tunisia-2000
Ukraine-2000
US-2000
New Zealand-2001
South Africa-2001
Azerbaijan—2002
Belarus—2002
Georgia--2002
India--2002
Latvia Uzbekistan--2002
Vietnam—2002
Estonia—2003
Guyana—2004
Moldova--2004
France, where the drug was developed, was the first country to license the use of mifepristone for medical abortion (in 1988). China was the second country to make mifepristone available to women interested in having a medical abortion (1988).
The United Kingdom (1991) and Sweden (1992) followed suit during the early 1990s. More recently, a number of other countries throughout Europe, Asia and elsewhere have made mifepristone available for medical abortion.1-4
Ref:
1 Creinin MD. Medical abortion regimens: historical context and overview. Am J Obstet Gynecol 2000;183(suppl):S3-S9.
2 Beverly Winikoff, Gynuity Health Projects, personal communication, March 7, 2005.
3 Kerli Hannus, The Family Planning Association of Estonia, personal communication, March 15, 2005.
4 Ivar Brod, Panam Pharmaceuticals, Inc., personal communication, March 18, 2005.
Overview of Medical Abortion (Early Options 2005)

10. Mechanism of Action: Mifepristone + Misoprostol
Necrosis of trophoblast

11. Route การใช้ยา misoprostol ( Cytotec)
กิน (oral)
เหน็บช่องคลอด (vaginal)
เหน็บทวารหนัก (rectal)
อมใต้ลิ้น (sublingual)
อมกระพุ้งแก้ม (buccal)

12. การใช้ยา misoprostol ในทางสูติกรรม
1. Cervical priming
2. Termination of pregnancy
3. Incomplete abortion
4. Induction of labour
5. Postpartum hemorrhage

13. WHO regimen + 24-48 h Up to 9 weeks since LMP 200 mg mifepristone
800 mcg misoprostol (vag, sublingual)
Success rate = 92-98%

14. Gestational Age
Mifepristone Dose
Misoprostol Dose, Route and Timing
Up to 9 weeks
200 mg orally
After hours, 800 mcg buccally, sublingually or vaginally for one dose
Between 9-12 weeks
After hours, 800 mcg vaginally followed by 400 mcg vaginally or sublingually every 3 hours for a maximum of 5 doses of misoprostol
Above 12 weeks
After hours, 400 mcg orally or 800 mcg vaginally followed by 400 mcg vaginally or sublingually every 3 hours for a maximum of 5 doses of misoprostol, administered in a healthcare facility

15. Mifepristone/misoprostol regimens Comparison of protocols
French Regimen
US: FDA Regimen
Evidence-Based Regimen
Mifepristone Dosage
600 mg (Day 1)
200 mg (Day 1)
Misoprostol Dosage
400 µg, PO
Or 1mg gemeprost, PV
400 µg, PO or 800 µg, PV
Gestational Limit
≤ 49 days
≤ 63 days
Location of misoprostol administration
At medical office/clinic
At medical office/clinic or at home
Timing of misoprostol administration
Day 2 or 3
Day 3
Day 2, 3, or 4
Timing of initial follow-up examination
Day 10 to 14
Day 14
Day 4 to 14
Number of clinic visits required
Three or more
Two or more
France: Labeled regimen
The mifepristone/misoprostol regimen is approved up to 49 days’ gestation. Women are required to orally take 600 mg of mifepristone (Mifegyne™). Thirty-six to forty eight hours later, women are required to either orally take 400µg (micrograms) of misoprostol or 1 mg of vaginally administer gemeprost (also a prostaglandin analog). Ten to fourteen days after taking mifepristone, the patient is required to return for a follow-up visit to determine whether the pregnancy has been terminated.
US: FDA approved regimen
The research that the FDA reviewed for approval was based on the original French regimen, developed more than a decade ago. The mifepristone/misoprostol regimen is approved up to 49 days’ gestation. The FDA approved regimen specifies that a woman orally take 600mg of Mifeprex™ and 400µg (micrograms) of misoprostol two days later (orally). Approximately fourteen days after taking mifepristone, the patient is required to return for a follow-up visit to determine whether the pregnancy has been terminated.
Evidence-based regimen
A number of studies have shown that alternative regimens to the FDA approved protocol are effective and safe. The most common modification involves decreasing the dose of mifepristone to 200 mg. Studies have also shown that misoprostol can be vaginally administered either one, two, or three days after mifepristone use, with no loss in efficacy, compared to the FDA-mandated two-day protocol. Other studies have shown that the mifepristone/misoprostol regimen can be extended up to 63 days’ gestation. Vast experience also supports the safety, efficacy, and acceptability of home-administration of misoprostol. Several professional organization guidelines incorporate these modifications.
Recent studies have called into question the need for a routine, in-person post-abortion visit, especially for terminations occurring ≤ 49 days’ gestation. Results from a mifepristone/misoprostol clinical trial conducted in China, Cuba, and India suggest that women who experience an incomplete abortion are able to identify their condition correctly. Investigation into possible alternatives to universal in-person follow-up, such as telephone follow-up with home pregnancy testing and in-person follow-up for selected patients, is ongoing.
Mifegyne website: Von Hertzen H. Research on regimens for early medical abortion. JAMWA ; 35(3): S ; Schaff E,  Fielding SL,  Westhoff C,  Ellertson C,  Eisinger Stadalius LS,  Fuller L.  Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: A randomized trial  JAMA. 2000;  284(15): ; Newhall E, Winikoff B. Abortion with Mifepristone and Misoprostol: Regimens, Efficacy, Acceptability and Future Directions. Am J Obstet Gyncol ; 183(2): S44-53; Grossman D, Ellertson C, Grimes D, Strickler J, Walker D, Harper C. Mandatory follow-up examinations after first-trimester induced abortion: A review. (Need to have full citation at some point); Harper C, Ellertson C, Winikoff B. Could American women use mifepristone-misoprostol pills safely with less medical supervision? Contraception ; 65: ; Ellertson C, Elul B, Winikoff B. Can women use medical abortion without medical supervision? Reproductive Health Matters ; 9:

16. Home regimen pregnancy < 9 week
Medabon Regimen
Home regimen pregnancy < 9 week
Day mifepristone 1 tab oral
Day misoprostol 4 tab vaginal or sublingual
Day follow up and contraception
Efficacy %
Abortion within 2-3 h( sublingual miso) or 3-6 h (vaginal miso) bleeding = 5-14 days

17. Mifepristone/misoprostol regimen Contraindications to use
Confirmed or suspected ectopic (extra-uterine) pregnancy
Allergy to either mifepristone or misoprostol
Presence of an intrauterine device (IUD)
Chronic systemic use of corticosteroids
Chronic adrenal failure
Coagulopathy or current therapy with anticoagulants
Inherited porphyria

18. Mifepristone/misoprostol regimen Side effects
Effects of abortion process
Cramping
Often described as similar to menstrual cramps
Vaginal bleeding
Median bleeding time days
Often described as similar to a heavy period or spontaneous miscarriage
Common side effects
Nausea
Vomiting
Diarrhea
Headache
Dizziness
Fever, chills, hot flashes, warmth
Some side effects, such as abdominal cramping and bleeding, are hallmarks of the abortion process itself. Many women and clinicians report cramps and abdominal pain similar to those associated with a heavy menstrual period. Vaginal bleeding can vary significantly in both duration and severity, and many report that the bleeding resembles a heavy period or a spontaneous miscarriage. One study of mifepristone used with a vaginal prostaglandin to treat women through 63 days’ gestation found that median blood loss was about 75 ml, compared with 50 ml typically lost during menses. The range of bleeding is correlated to the length of gestation and can extend up to several hundred milliliters. Light bleeding and spotting can last for 1-3 weeks. Reported median bleeding times range from 9-13 days. The heaviest period of bleeding typically occurs when the abortion is occurring and persists for 1 to 4 hours.
Side effects of the medications include nausea, vomiting, diarrhea, fever, and chills. In most cases, side effects can be managed with appropriate counseling and symptomatic treatments, such as oral analgesics for pain. Temperature elevation (defined as more than 100.4○ F or 38○ C) that is sustained (more than four hours) or begins later than 6 to 8 hours after misoprostol administration warrants clinical assessment.
Rodger MW, Baird DT. Blood loss following induction of early abortion using mifepristone (RU 486) and a prostaglandin analog (gemeprost). Contraception. 1997; 56(3): ; Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med. 1998; 338(18): ; ACOG Practice Bulletin. 2001; no. 26.

19. Medical abortion ข้อดี ข้อด้อย Failed cases need surgical methods
ปลอดภัย
สะดวก
Multi-steps(ต้องมาโรงพยาบาลหลายครั้ง
No anesthesia
Women’s greater control

20. "Women who die of unsafe abortion ; they are not dying because of diseases that we cannot treat they are dying because societies (and I might add including some of our medical fraternity in Thailand and in the world for that matter), have yet to make the decision that their lives are worth saving."
ศาสตราจารย์กำแหง จาตุรจินดาประธานมูลนิธิเพื่อสิทธิอนามัยการเจริญพันธุ์ของสตรีไทย IWAC 2012

21. Thank you!