Transcript Rodica Comendant - International Consortium for Medical Abortion

Medical abortion with
mifepristone and misoprostol:
overview
Dr. Rodica Comendant,
ICMA Operations Coordinator
Bangkok, Thailand, March 2012
Outlines
• Definition of MA, what is known, the use in
the world
• The actual trends in MA
• The regimens for 10-12 weeks, 2nd
trimester
• Misoprostol alone regimen
• Alternative ways for follow up
What is medical abortion?
• A way of inducing termination of
pregnancy with medicines (pills)
• A “non-surgical” abortion
• The regimen for first trimester medical
abortion, consists of two drugs, included in
2005 on the WHO Essential Medicines list:
mifepristone followed 1–3 days later by
misoprostol
Why medical abortion is important?
Medical abortion can make abortion:
 earlier,
 more accessible,
 safer,
 less traumatic,
 less medicalised and less expensive.
 There is no medical reason for adolescents do
not have medical abortion.
 It has increased access to safe abortion and
reduced maternal mortality, including in legally
restricted settings.
What we know today about MA?
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Registered in 50 countries (2011)
Use by 2.5 - 3 million women outside of China
Use by more than 22 million women in China
Good efficacy : 92-97%
Extremely good safety record, lower risk of
infection and trauma than surgery
• Women like the method very much (it’s private,
natural and similar to menstruation)
What is mifepristone? How does it work?
• Antiprogestin compound
•
Discovered in 1980 in Russel Uklaaf laboratory
• First clinical trial in 1982, Geneva
• Binds to progesterone receptor to block action of
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progesterone
Increases endogenous prostaglandins
Increases uterine contractility and sensitivity to
prostaglandins
Decidua and trophoblast separate
Cervix softens and dilates, facilitating abortion
What is misoprostol? How does
misoprostol work?
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Prostaglandin E1 analogue, approved for prevention
and treatment of gastric ulcers
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Drug causes contractions of smooth muscles of the
uterus -> empties the uterus
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Drug can soften the cervix -> increases dilation for
interuterine procedures, facilitates expulsions
Mechanism of Action in MA:
Mifepristone + Misoprostol
Progesterone Blockade
Decidual
Necrosis
Rhythmic
Uterine
Contractions
Detachment
Cervical
Ripening
Expulsion
© Lisa Penalver
Abortion
Misoprostol: routes of
administration
Oral
Rapid absorption (peak 30 mins)
Levels fall sharply in 1-2 hours
Vaginal
Peak later (80 mins) but lower
Higher levels longer in plasma
Buccal
Later, lower peak, sustained
levels (similar to vaginal)
Sublingual Rapid absorption, high peak
levels, sustained levels
Rectal
Lower peak but higher levels
longer than oral
Vaginal, oral and sublingual
pharmacokinetics
Tang, et al, 2002
Contraindications to method
• Suspected ectopic pregnancy (rule out)
• IUD in place (take out)
• Chronic adrenal failure
• Current long term corticosteroids
• Known allergy to the medications
• Clotting disorder/anticoagulant therapy
• Inherited porphyria
Expected side effects:
go away within several hours and don’t
need serious medical treatment
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Pain, cramping
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Bleeding
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Gastrointestinal side effects
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Fever, chills
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Dizziness, headache
Safety of MA
• Uterine blood loss in surgical or medical
abortion is the same
• With medical bleeding lasts more days
• 95.000 MA, complication (heavy bleeding)
- 2.2 per 1000 women (PPF, USA, 20012005). Mortality 1,1 per 100.000(one
death)
• France ~1000.000 abortion, no one death
Safety of Medical Abortion
Medical Abortion
Early Surgical abortion
Transfusion:
0,2%
0,1%
Aspiration to stop bleeding (0,4-2%)
Infection
0,09-0,5%
0.2-5.4%
French regimen (early 90es), for 49
days LMP
Visit 1:
Patient eligibility, counseling (!)
Swallow 3 tabs mifepristone
Visit 2:
+36-48 hr
Oral Misoprostol (400 µg)
3-4 hour monitoring in clinic
Visit 3:
+10-12 days
Follow-up visit
Recommended mifepristone plus
misoprostol regimens (WHO 2012)
Up to 9 completed weeks (63 days) LMP
• 200 mg mifepristone followed after 24-48
hours by
• 800 µg misoprostol, administered vaginally,
sublingually or buccally
Or, for up to 7 completed weeks (49 days)
• 400 µg oral misoprostol.
Home Use of Misoprostol
• Overwhelmingly preferred choice in U.S.
– 98-99% (n = 4345) Schaff, 1998, 1999,
2000
• Similar preference in developing countries:
– Vietnam 80% (n =112) Elul, et al., 2000
– Tunisia 87% (n =191) Elul, et al., 2000
• Home administration recently approved in
France, in many EU countries
Is misoprostol in clinic
needed for safety reasons?
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No serious adverse events in 4 hours postmisoprostol in clinic – 1059 patients in 4
developing countries
• Pop Council trial in 2121 U.S. women: 4
transfusions, none during clinic waiting
time
• Schaff study of 2295 women: no
interventions required within 4 hours of
misoprostol
Regimens in later first trimester:
10-12 weeks LMP
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Beginning to be more widely used
• 200mg mifepristone orally followed after 36–48 hours by
800 µg vaginal misoprostol, administered in a health
facility.
• A maximum of 4 further doses of misoprostol 400 µg
may be administered at 3-hourly intervals, vaginally or
orally.(WHO, 2012)
• A clinic-based procedure that takes several hours to a
day
• Many women prefer the faster surgical approach,
especially when that is offered as a rapid outpatient
procedure
Regimens for second trimester: 12-21 weeks
• 200 mg mifepristone followed after 36-48 hours
by
• 400 µg oral or 800 µg vaginal misoprostol
followed by 400 µg vaginal or sublingual
misoprostol every 3 hours up to a maximum of 5
doses, administered in a health facility.
• After 24 weeks gestation, the dose of
misoprostol should be reduced. (WHO, 2012)
Alternative follow-up: checklists
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Clark et al. Ob & Gyn 2010, N=>3000 :
simple checklist works
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Simple checklist identified all ongoing
pregnancies
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Checklist also identified all women needing
any other additional care for their medical
abortion
A semi-quantitative pregnancy test
+ the checklist
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The semi-quantitative pregnancy test
is an accurate alternative method of
follow-up
The semi-quantitative pregnancy test
correctly identified all ongoing
pregnancies
The acceptability and feasibility of
using simple semi-quantitative
pregnancy tests with a simple
checklist are now under the research
The routine use of ultrasound – not
needed!
• Total of 4484 women seeking MA in US
• Women provided their LMP + vaginal
exam
• The estimations were compared to
ultrasound data
• Conclusion: LMP and physical exam,
without use of ultrasound are highlely
efective for early MA
H. Bracken, W. Clark, etc. Alternative to routine ultrasound for eligibility assessment
prior to early termination of pregnancy with mifepristone-misoprostol, BJOG, 2011
MA safely provided by mead-level
providers
(the Lancet, 2011)
• A study in Nepal, 1295 women, randomly
assigned to receive the care to a doctor or
to a mead-level providers
• Similar safety and effectiveness
Misoprostol alone for abortion
• Induced abortion
(0-12 weeks): 800g
vaginally 12-hrly
• Missed abortion
(0-12 weeks)800g
vaginally 3-hrly
OR
• 600g sublingually 3-hrly
• Incomplete abortion (0-12 weeks)600g orally
stat.
• Induced abortion
(13-24 weeks)400g
vaginally 3-hrly x5
Weeks A & Faundes A. International Journal
of Gynecology and Obstetrics 2007;99:S156-9.
Misoprostol alone versus
mifepristone+misoprostol regimen
• A study in Vietnam, 400 women
• Randomized to two groups: two doses of 800
mcg buccal miso or 200 mife+800 mcg miso
• In miso group the efficacy 76,2%, in mife+miso –
96,5%
• Ongoing pregnancy in miso group -16,6%
• In mife+miso group – 1,5%
Published in Contraception, 2010
Thank you!
Questions?