misoprostol-only regimens for medical abortion department of reproductive health and research world...

MISOPROSTOL-ONLY REGIMENSFOR MEDICAL ABORTIONDepartment of Reproductive Health and ResearchWorld Health OrganizationGeneva

HELENA VON HERTZEN

HvH FIAPAC MOSCOW OC.2005 *

HvH FIAPAC MOSCOW OC.2005 *MISOPROSTOLSynthetic analogue of naturally occurring prostaglandin E1Approved in >80 countries (prevention and treatment of gastric and duodenal ulcers; Brazil, Egypt, France also other indications)Safe and well toleratedTablets can be kept at room temperature when packed in aluminium blisters


HvH FIAPAC MOSCOW OC.2005 *Mean plasma concentrations of misoprostol acid over time with oral and vaginal administration


PVL_PCC-02_EC/*

vaginal administration

-

=

Oral administration

(Zieman, 1997)



Diagr1

024.53.333333333340

58.333333333384.274.833333333393.5

183.1666666667135.2124.3333333333124.6666666667

133.288.6132234.6666666667

184.5105.3178.5355.3333333333

27389255374.8

245.2122.3333333333278.8333333333342.6

364135.2222222222348.3333333333210

453.6666666667165.5555555556240240

vaginal

oral

sulingual 0.2mg

sulingual 0.4mg

Min

Montevideo Units

Blad1

MONTEVIDEO

min0306090120150180210240

CYTOTECMONTEVIDEOVAGINALTSE means

mean058.3183.2133.2184.5273.0245.2364.0453.7

SD0106.6181.175.084.6101.2145.0205.7230.9

n555555555

SE047.781.033.637.845.364.892.0103.263.2

CYTOTECMONTEVIDEOORALT

mean24.584.2135.288.6105.389.0122.3135.2165.6

SD31.575.296.985.7129.562.9108.8112.4168.3

n10.010.010.010.010.010.010.010.010.0

SE10.023.830.627.141.019.934.435.553.233.2

CYTOTECMONTEVIDEOSUBLINGUALT0.2 MG

mean3.374.8124.3132.0178.5255.0278.8348.3

SD2.6110.8118.6105.8186.0245.1198.6243.4

n6.06.06.06.06.06.06.06.0

SE1.145.248.443.276.0100.081.199.470.5

CYTOTECMONTEVIDEOSUBLINGUALT0.4 MG

mean40.093.5124.7234.7355.3374.8342.6321.8

SD56.180.482.4187.7279.8344.4333.5241.3

n66666666

SE22.932.833.676.6114.2140.6136.198.590.4

minmeansmeansmeansmeans

VAGINALORALSUBL 0.2SUBL 0.4

024.53.340.0

3058.384.274.893.5

60183.2135.2124.3124.7

90133.288.6132.0234.7

120184.5105.3178.5355.3

150273.089.0255.0374.8

180245.2122.3278.8342.6

210364.0135.2348.3321.8

240453.7165.6

TONUS

min0306090120150180210240

CYTOTECTONUSVAGINALTSE means

mean13.620.140.340.436.638.740.945.046.3

SD3.76.114.711.29.18.610.08.89.7

n999999999

SE1.22.04.93.73.02.93.32.93.23.3

CYTOTECTONUSORALT

mean12.041.350.435.730.431.036.340.234.8

SD8.012.18.912.410.210.611.813.315.1

n101010101010101010

SE2.53.82.83.93.23.43.74.24.83.7

CYTOTECTONUSSUBLINGUALT0.2 MG

mean17.533.753.041.537.737.541.542.5

SD9.513.89.97.99.811.810.19.9

n66666666

SE3.95.64.03.24.04.84.14.04.3

CYTOTECTONUSSUBLINGUALT0.4 MG

mean13.430.855.858.450.651.853.655.0

SD1.912.78.88.416.720.022.322.3

n66666666

SE0.85.23.63.46.88.29.19.16.5

minmeansmeansmeansmeans

VAGINALORALSUBL 0.2SUBL 0.4

013.612.017.513.4

3020.141.333.730.8

6040.350.453.055.8

9040.435.741.558.4

12036.630.437.750.6

15038.731.037.551.8

18040.936.341.553.6

21045.040.242.555.0

24046.334.8

Blad2

0306090120150180210240

vaginal13.620.140.340.436.638.740.94546.3

oral24.584.2135.288.6105.389122.3135.2165.6

sulingual 0.2mg3.374.8124.3132178.5255278.8348.3

sulingual 0.4mg4093.5124.7234.7355.3374.8342.6321.8

Blad2

0000

0000

0000

0000

0000

0000

0000

0000

0000

vaginal

oral

sulingual 0.2mg

sulingual 0.4mg

MIN

TONUS

Blad3

0306090120150180210240

vaginal058.3183.2133.2184.5273.0245.2364.0453.7

oral24.584.2135.288.6105.389.0122.3135.2165.6

sulingual 0.2mg3.374.8124.3132.0178.5255.0278.8348.3

sulingual 0.4mg40.093.5124.7234.7355.3374.8342.6

Blad3

0000

0000

0000

0000

0000

0000

0000

0000

0000

vaginal

oral

sulingual 0.2mg

sulingual 0.4mg

MIN

MONTEVIDEO UNITS

HvH FIAPAC MOSCOW OC.2005 *INDUCING EARLY ABORTIONOral misoprostolStudyRegimen N Gestational Success age (wks) Rabe et al.(1987) 0.4mg x 2 100 9 -1211% 0.2mg x 2 100 9 -12 9% Norman et al.(1991) 0.2mg 0.6mg 40

HvH FIAPAC MOSCOW OC.2005 *INDUCING EARLY ABORTIONVaginal misoprostolStudyRegimenN Gestational age (wks) Continuing pregnancy Carbonell et al. (1997)0.8mgx3+(48h) 175

HvH FIAPAC MOSCOW OC.2005 *COMPARISON OF TWO ROUTES AND TWO INTERVALS OF MISOPROSTOLFOR TERMINATION OF EARLY PREGNANCY: RANDOMIZED, CONTROLLED MULTICENTRE TRIAL11 centres: Armenia, Cuba, Georgia, India, Mongolia and Viet Nam2066 women up to 63 days LMPThree doses of 0.8mg misoprostol

Group ISublingual, 3-hour intervalGroup IISublingual, 12-hour intervalGroup IIIVaginal, 3-hour intervalGroup IVVaginal, 12-hour interval


HvH FIAPAC MOSCOW OC.2005 *Baseline characteristicsCharacteristicSublingual 3hSublingual 12hVaginal 3h Vaginal 12h (n=517) (n=516) (n=516) (n=517) Age (years)26.7 5.8 26.7 5.8 26.5 5.726.6 5.4Nulliparity22142.720139.021241.120639.8Previous induced abortion18435.618535.918836.419637.9Length of pregnancy (days)*, events(%) 29-4924547.424647.724948.323946.2 50-5614427.914628.313726.615129.2 57-6312824.812424.013025.212624.4 * Length of pregnancy assessed by ultrasound


HvH FIAPAC MOSCOW OC.2005 *Outcomes of treatment by groupGroupOutcomeNo. ofPercentages excludingcasesundetermined cases (95% CI)

Sublingual 3-hour, (n=517)Complete abortion 43185.9 (82.5 to 88.8)Continuing pregnancy 29 5.8 ( 3.9 to 8.2)Sublingual 12-hour, (n=516)Complete abortion 39979.3 (75.5 to 82.8)Continuing pregnancy 47 9.3 ( 6.9 to 12.2)


HvH FIAPAC MOSCOW OC.2005 *Outcomes of treatment by groupGroupOutcomeNo. ofPercentages excludingcasesundetermined1 cases (95% CI)

Vaginal 3-hour, (n=516)Complete abortion 43487.1 (83.9 to 90.0)Continuing pregnancy 20 4.0 ( 2.5 to 6.1)Vaginal 12-hour, (n=517)Complete abortion 42585.5 (82.1 to 88.5)Continuing pregnancy 25 5.0 ( 3.3 to 7.3)


HvH FIAPAC MOSCOW OC.2005 *Failure to achieve complete abortion*Treatment groupNo. ofPercentagesRR 95% CIDifference 95% CIfailures/no. (%) (%)of subjects

Sublingual 3-hour71/50214.11.1(0.8 to 1.5) 1.3(-2.9 to 5.5)

Sublingual 12-hour 104/50320.71.6(1.2 to 2.1)7.8(3.2 to 12.4)

Vaginal 3-hour64/49812.9 1(Reference)0.0(Reference)

Vaginal 12-hour 72/49714.51.1(0.8 to 1.5)1.6(-2.6 to 5.9)

* Excluding undetermined cases


HvH FIAPAC MOSCOW OC.2005 *Failure to achieve complete abortion*Length of pregnancyNo. ofPercentagesRR 95% CIDifference 95% CI (days)**failures/no. (%) (%)of subjects

29-49 132/93514.11(Reference) 0.0(Reference)

50-56 88/57115.41.1(0.9 to 1.4) 1.3(-2.4 to 5.0)

57-63 91/49318.51.3 (1.0 to 1.7)4.3 (0.2 to 8.4)

* Excluding undetermined cases** Length of pregnancy assessed by ultrasound


HvH FIAPAC MOSCOW OC.2005 *Failure to abort*Treatment groupNo. ofPercentagesRR 95% CIDifference 95% CIfailures/no. (%) (%)of subjects

Sublingual 3-hour29/502 5.81.4(0.8 to 2.5) 1.8(-0.9 to 4.4)

Sublingual 12-hour 47/503 9.32.3(1.4 to 3.9)5.3 (2.3 to 8.4)

Vaginal 3-hour20/4984.01.0(Reference)0.0(Reference)

Vaginal 12-hour25/4975.01.3 (0.7 to 2.2)1.0(-1.6 to 3.6)

* Excluding undetermined cases


HvH FIAPAC MOSCOW OC.2005 *Failure to abort*Length of pregnancyNo. ofPercentagesRR 95% CIDifference 95% CI (days)**failures/no. (%) (%)of subjects

29-49 44/9354.7 1(Reference) 0.0(Reference)

50-56 33/5715.81.2 (0.8 to 1.9) 1.1(-1.3 to 3.4)

57-63 44/4938.91.9 (1.3 to 2.8) 4.2 (1.4 to 7.1)

* Excluding undetermined cases** Length of pregnancy assessed by ultrasound


HvH FIAPAC MOSCOW OC.2005 *Side-effects after 0.8 mg misoprostol in two trials (with and without mifepristone pre-treatment) Side-effectOral/sublingual vaginal Nausea31.1 % / 27.0% 22.5% / 25.9%Vomiting17.8% / 10.0% 6.9% / 6.3%Fever 4.7% / 7.6% 4.3% / 5.6%Pain71.9% / 79.6% 73.3% / 79.7%

Figures in red = with mifepristone


HvH FIAPAC MOSCOW OC.2005 *Efficacy of medical abortion in two trials (with and without mifepristone pre-treatment) RegimenNo. Outcome percentages Mife+O/O 683/740 complete abortion 94.5 9/740 continuing pregnancy 1.2

Mife+V/O 702/741 complete abortion 96.6 1/741 continuing pregnancy 0.1

Mife+V 690/738 complete abortion 95.4 2/738 continuing pregnancy 0.3

Miso V, 3h 434/516 complete abortion 87.1 20/516 continuing pregnancy 4.0


misoprostol-only regimens for medical abortion department of reproductive health and research world...

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