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8/13/2019 Aborto y Misotrol

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Spontaneous abortion: ManagementAuthorsTogas Tulandi, MD, MHCMHaya M Al-Fozan, MDSection Editor

Robert L arbieri, MDDe!uty EditorSandy " Fal#, MDDisclosuresAll to!ics are u!dated as ne$ e%idence beco&es a%ailable and our!eer re%ie$ !rocessis co&!lete'Literature re%ie$ current through( Se! )*+' This to!ic last u!dated( abr )., )*+)'

/0TR1D2CT/10 3 S!ontaneous abortion, also #no$n as &iscarriage, re4ers to a!regnancy that ends s!ontaneously be4ore the 4etus has reached a %iable gestational age'The &anage&ent o4 di44erent ty!es o4 s!ontaneous abortion $ill be discussed here'

1ther as!ects o4 s!ontaneous abortion, including the clinical &ani4estations anddiagnosis o4 the di44erent ty!es o4 abortion, are re%ie$ed se!arately' 5See 6S!ontaneousabortion( Ris# 4actors, etiology, clinical &ani4estations, and diagnostic e%aluation6'7

THREATE0ED A1RT/10 3 8o&en $ith threatened abortion ha%e traditionallybeen &anaged e9!ectantly until their sy&!to&s resol%e, a de4initi%e diagnosis o4non%iable !regnancy can be &ade, or there is !rogression to an ine%itable, inco&!lete,or co&!lete abortion'

The use o4 !rogestins to reduce the ris# o4 &iscarriage a&ong $o&en $ith threatened

abortion is contro%ersial' A &eta-analysis that included 4our rando&ized trials $ith atotal o4 .)+ $o&en 4ound that the rate o4 s!ontaneous abortion $as statisticallysigni4icantly lo$er $ith !rogestin treat&ent co&!ared $ith !lacebo or no treat&ent 5+.%ersus ): !ercent; relati%e ris# *'


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SEBT/C A1RT/10 3 Sus!ected se!tic abortion $ith retained !roducts o4 conce!tionshould be &anaged by(

Stabilizing the !atient

1btaining blood and endo&etrial cultures

Bro&!tly ad&inistering !arenteral broad s!ectru& antibiotics 5eg, clinda&ycin=** &g e%ery eight hours and genta&icin< &g#g daily $ith or $ithouta&!icillin) g e%ery 4our hours; or a&!icillin and genta&icin and &etronidazole


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A co&!lete abortion theoretically should not reuire thera!y, but co&!lete abortionsgenerally cannot be reliably distinguished 4ro& inco&!lete abortions either clinically orultrasonogra!hically' As a result, so&e !ro%iders !er4or& suction curettage in all o4these !atients @=' Due to a !ossible ris# o4 intrauterine adhesions, $e do not ad%ocatethis a!!roach' /n addition, treat&ent o4 intrauterine adhesions is not al$ays 4ollo$ed by

a !regnancy' 5See GSurgical &anage&entGbelo$ and 6/ntrauterine adhesions6'7

The surgical &anage&ent o4 co&!lete abortion is not based u!on data 4ro& co&!arati%etrials' /t see&s clear that surgery is necessary 4or $o&en $ith e9cessi%e bleeding,unstable %ital signs, or ob%ious signs o4 in4ection' 8hether the uterus should bee%acuated in unco&!licated cases needs to be deter&ined by studies that co&!are%arious treat&ent a!!roaches and consider the ty!e o4 &iscarriage 5inco&!lete orco&!lete7, the gestational age, and the clinical status and !re4erences o4 the &other' /nour e9!erience, i4 the ultrasound sho$s an e&!ty uterus and the bleeding is &ini&al, no4urther action is needed'

/0C1MBLETE, /0E/TALE, A0D M/SSED A1RT/10 3 8o&en $ith aninco&!lete, ine%itable, or &issed abortion docu&ented by ultrasound e9a&ination can

be &anaged surgically, &edically, or e9!ectantly' Syste&atic re%ie$s o4 rando&izedclinical trials o4 surgical, &edical, and e9!ectant &anage&ent o4 $o&en $ith 4irsttri&ester &issed or inco&!lete abortion generally concluded that all o4 the thera!ies$ere e44ecti%e, but co&!lete e%acuation $ithin . hours $as &ore li#ely $ith surgicalthan &edical &anage&ent and &ore li#ely $ith &edical than e9!ectant &anage&ent@+*-+)' These analyses $ere li&ited by &issing data, di44erent a!!roaches to &edicaland e9!ectant &anage&ent, and nonstandardized outco&es' Maor co&!lications $erein4reuent 4or all o4 the &ethods, and !atient satis4action could not be assessed'

Subseuent to these syste&atic re%ie$s, a rando&ized trial 5M/ST7 co&!aring surgical,&edical, and e9!ectant &anage&ent o4 4ailed !regnancy in +)** $o&en re!orted thatthe incidence o4 in4ection $as ) to !ercent 4or all three grou!s @+; thus, the ris# o4in4ection is not an i&!ortant %ariable in choosing the thera!eutic a!!roach'

Surgical &anage&ent 3 The con%entional treat&ent o4 4irst or early second tri&ester4ailed !regnancy is dilatation and curettage 5DIC7 or dilatation and e%acuation 5DIE7to !re%ent !otential he&orrhagic and in4ectious co&!lications 4ro& the retained

!roducts o4 conce!tion @+.' This !rocedure carries anesthesia ris#s and co&!licationssuch as uterine !er4oration, intrauterine adhesions, cer%ical trau&a, and in4ection, $hich

&ight lead to subseuent in4ertility or ecto!ic !regnancy @+


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based on a &eta-analysis that 4ound $o&en gi%en !eriabortal antibiotics had a .)!ercent lo$er ris# o4 in4ection @+=' These trials in%ol%ed $o&en undergoing inducedabortion, but it is li#ely si&ilar bene4its $ould be obser%ed 4or $o&en undergoingsurgical e%acuation o4 a 4ailed !regnancy' Ho$e%er, the only rando&ized trial thate%aluated antibiotic !ro!hyla9is be4ore curettage 4or inco&!lete abortion did not

obser%e a signi4icant decrease in 4ebrile &orbidity @)*'

Medical treat&ent 3 The a%ailability o4 e44ecti%e &edical thera!ies 4or inducingabortion has created ne$ o!tions 4or $o&en $ho $ant to a%oid surgery and in areas$here surgical inter%ention is not !ractical' Miso!rostol5a !rostaglandin E+ analog7 isthe &ost co&&only used such agent' /ts sa4ety and e44ecti%eness ha%e been established

by &ulti!le rando&ized and controlled trials @)+,))' The ad%antages o4 &iso!rostolo%er other drugs 5including !rostaglandin E)7 are its lo$ cost @), lo$ incidence o4side e44ects $hen gi%en intra%aginally, stability at roo& te&!erature, and readya%ailability' The ris# o4 a &aor co&!lication is rare'

The e44icacy o4 &iso!rostol4or &edical &anage&ent o4 !regnancy 4ailure in the 4irsttri&ester $as illustrated in a large, $ell-designed trial in $hich :


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The o!ti&u& dose and route and 4reuency o4 ad&inistration ha%e not been established'/n a consensus !a!er by an e9!ert grou! con%ened by the 8orld Health 1rganization in)**?, t$o di44erent regi&ens o4 &iso!rostol$ere !ro!osed @(

For &issed abortion J ** &cg !er %agina& 1R :** &cg sublingually 5each o4

these is a single dose7 For inco&!lete abortion J :** &cg orally 5single dose7

1ur !re4erence is to use &iso!rostol.** &cg !er %agina& e%ery 4our hours 4or 4ourdoses to ta#e ad%antage o4 the increased e44ecti%eness o4 the %aginal route $hile&ini&izing the ris# o4 side e44ects, $hich are dose and route de!endent' The e9!ulsionrate is ?* to =* !ercent $ithin ). hours; thus, so&e $o&en $ill still reuire surgicale%acuation' Ho$e%er, the i&&ediate, short-ter&, and &ediu&-ter& &edicalco&!lications associated $ith &iso!rostol use are signi4icantly lo$er than $ith surgery@)'

A co&bination o4 a !rogesterone antagonist 5&i4e!ristone7 and &iso!rostol5.** &cgorally7 has also been used @=' Due to lo$ seru& !rogesterone le%els in $o&en $ithabnor&al !regnancy @.*, the %alue o4 adding a !rogesterone antagonist is uestionableand e9!ensi%e' This hy!othesis $as su!!orted by a !ros!ecti%e cross-o%er trial and arando&ized controlled trial, both o4 $hich re!orted that &iso!rostol alone or aco&bination o4 &iso!rostol and &i4e!ristone had si&ilar success rates in treat&ent o4early !regnancy 4ailure @.+,.)' 5See 6Thera!eutic use and ad%erse e44ects o4

!rogesterone rece!tor antagonists and selecti%e !rogesterone rece!tor &odulators6'7

Batients $ho are treated &edically are instructed to go to the e&ergency de!art&ent i4they de%elo! e9cessi%e bleeding' Tissues that are !assed %aginally should be !laced in acontainer and brought to the hos!ital 4or analysis'

The long-ter& conce!tion rate and !regnancy outco&e are si&ilar 4or $o&en $houndergo &edical or surgical e%acuation 4or early !regnancy 4ailure @.'

Methotre9ateis not used in &anage&ent o4 s!ontaneous abortion'

Second tri&ester 3 Second tri&ester abortion is associated $ith higher rates o4co&!lications than 4irst tri&ester abortion @..' For e9a&!le, u! to +* !ercent o4$o&en undergoing induced &edical abortion $ill reuire hos!italization 4or &edical,

social, or geogra!hical reasons @.


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noninter%ention @++' Rando&ized trials co&!aring &edical &anage&ent to EM ha%ere!orted si&ilar rates o4 success4ul e%acuation @


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on se%eral 4actors, including the sco!e o4 costs considered in the analysis and theco&&unity in $hich the costs are incurred @:-::'

B1STA1RT/10 CARE A0D C120SEL/0 3 8o&en are ad%ised to &aintain!el%ic rest 5ie, nothing !er %agina7 until t$o $ee#s a4ter e%acuation or !assage o4 the

!roducts o4 conce!tion, at $hich ti&e coitus and use o4 ta&!ons &ay be resu&ed' /t iscusto&ary to ad%ise that !regnancy be de4erred 4or t$o to three &onths, althoughse%eral studies ha%e sho$n no greater ris# o4 ad%erse outco&e $ith a shorterinter!regnancy inter%al @:?-?*' Any ty!e o4 contrace!tion, including !lace&ent o4intrauterine contrace!tion @?+, &ay be started i&&ediately a4ter the abortion has beenco&!leted' 5See 6Bost!artu& and !ostabortion contrace!tion6'7

Light %aginal bleeding can !ersist 4or a cou!le o4 $ee#s a4ter the abortion' Batientsshould call their !ro%ider i4 hea%y bleeding, 4e%er, or abdo&inal !ain de%elo!s' Mensesty!ically resu&e $ithin si9 $ee#s; i4 nor&al &enses do not resu&e, then the !resenceo4 a ne$ !regnancy or, rarely, gestational tro!hoblastic disease should be considered'

Although rare, intrauterine adhesions 5also #no$n as Asher&anGs syndro&e7 couldoccur a4ter surgical e%acuation o4 the uterus' /n the se%ere 4or&, &enses do not resu&eor are scanty'

Alloi&&unization !re%ention 3 8o&en $ho are Rh5D7-negati%e and unsensitizedshould recei%e Rh5D7-i&&une globulin 4ollo$ing surgical e%acuation or u!on diagnosisi4 &edical &anage&ent or EM is !lanned' A dose o4


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F2T2RE REBR1D2CT/E /SS2ES 3 The o%erall ris# o4 &iscarriage in 4uture!regnancy is a!!ro9i&ately )* !ercent a4ter one &iscarriage, ) !ercent a4ter t$o&iscarriages, and . !ercent a4ter three or &ore &iscarriages @*'

There also a!!ears to be an increased ris# o4 !reter& deli%ery in subseuent !regnancies

@+,)' The ris# increases $ith increasing nu&ber o4 &iscarriages 51R +'*


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e%acuation is a &ore success4ul !ri&ary thera!y than &edical or e9!ectant&anage&ent; the e44ecti%eness o4 the latter t$o a!!roaches de!ends u!on theduration o4 ti&e allo$ed be4ore secondary surgical inter%ention and u!on thety!e o4 non%iable !regnancy' Bostabortal in4ection rates are si&ilar 4or all threea!!roaches, and the 4reuency o4 other co&!lications is lo$' For these reasons,

the choice o4 treat&ent should be based u!on !atient !re4erences' 5SeeG/nco&!lete, ine%itable, and &issed abortionGabo%e'7

8e reco&&end surgical thera!y 4or $o&en $ho are unstable because o4

bleeding or in4ection and 4or $o&en $ho $ant i&&ediate, de4initi%e treat&ent5rade +A7' 5See GSurgical &anage&entGabo%e'7

8e reco&&end treat&ent $ith &iso!rostol4or $o&en $ho $ant to a%oid a

surgical !rocedure, but do not $ant to $ait 4or s!ontaneous !assage o4 !roductso4 conce!tion to occur 5rade +A7' Se%enty to =* !ercent $ill ha%e a success4uloutco&e $ith &edical &anage&ent alone' 5See GMedical treat&entGabo%e'7

8e reco&&end e9!ectant &anage&ent 4or stable $o&en $ho do not $ant any

&edical or surgical inter%ention, and are $illing to $ait days to $ee#s 4or

e9!ulsion to occur 5rade +A7' leeding and cra&!ing &ay be !rolonged andsurgical e%acuation &ay still be reuired, but as &any as * !ercent o4 $o&en$ill ha%e a success4ul outco&e $ith e9!ectant &anage&ent alone' 5SeeGE9!ectant &anage&entGabo%e'7

2se o4 2!ToDate is subect to the Subscri!tion and License Agree&ent'

REFERENCES

+' 8ahabi HA, Fayed AA, Es&aeil SA, Al Peidan RA' Brogestogen 4or treatingthreatened &iscarriage' Cochrane Database Syst Re% )*++; (CD**


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++'0anda , Beloggia A, ri&es D, et al' E9!ectant care %ersus surgical treat&ent4or &iscarriage' Cochrane Database Syst Re% )**:; (CD**


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*' el-Re4aey H, Raase#ar D, Abdalla M, et al' /nduction o4 abortion $ith&i4e!ristone 5R2 .:7 and oral or %aginal &iso!rostol' 0 Engl " Med +==


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.=' 8ieringa-de 8aard M, os ", onsel ", et al' Manage&ent o4 &iscarriage( arando&ized controlled trial o4 e9!ectant &anage&ent %ersus surgicale%acuation' Hu& Re!rod )**); +?()..


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/niciar sesiYn

0ue%a bVsueda

/n4or&aciYn !ara el !aciente

0o%edades

Calculadoras

misoprostol an

ac# to Search ResultsMiso!rostol( Drug in4or&ation

Find BrintMiso!rostol( Drug in4or&ation

Clic# here to access additional search results in Le9ico&! 1nline'Co!yright +=?-)*+ Le9ico&!, /nc' All rights reser%ed'5For additional in4or&ation see 6Miso!rostol( Batient drug in4or&ation6and see6Miso!rostol( Bediatric drug in4or&ation67

For abbre%iations and sy&bols that &ay be used in Le9ico&! 5sho$ table7ALERT( 2'S' o9ed 8arning

The FDA-a!!ro%ed labeling includes a bo9ed $arning' See 8arningsBrecautionssection 4or a concise su&&ary o4 this in4or&ation' For %erbati& $ording o4 the bo9ed$arning, consult the !roduct labeling or $$$'4da'go%'

rand 0a&es( 2'S' Cytotec

rand 0a&es( Canada 0o%o-Miso!rostol;

BMS-Miso!rostol

Bhar&acologic Category Brostaglandin

Dosing( Adult

Prevention of NSAID-inu!e gastri! ul!ers:1ral( )** &cg . ti&es daily $ith 4ood;

i4 not tolerated, &ay decrease dose to +** &cg . ti&es daily $ith 4ood; last dose o4the day should be ta#en at bedti&e
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Mei!al termination of pregnan!y:1ral( Re4er to Mi4e!ristone &onogra!h'

"abor inu!tion or !ervi!al ripening #unlabele uses$: /ntra%aginal( )< &cg 5+. o4+** &cg tablet7; &ay re!eat at inter%als no &ore 4reuent than e%ery -: hours' Donot use in !atients $ith !re%ious cesarean deli%ery or !rior &aor uterine surgery

5AC1, )**=b7'

Prevention of postpartum %emorr%age #unlabele use$:1ral( :** &cg as a singledose ad&inistered i&&ediately a4ter deli%ery; to be used in settings $hereo9ytocin is not a%ailable 5F/1, )*+)7'

&reatment of postpartum %emorr%age #unlabele use$:Sublingual( ** &cg as asingle dose; to be used in settings $here o9ytocin is not a%ailable' 2se caution i4 a

!ro!hylactic dose $as already gi%en, es!ecially i4 ad%erse e%ents $ere obser%ed5F/1, )*+)7'

&reatment of in!omplete abortion #unlabele use$:1ral( :** &cg as a single dose5AC1, )**=a7

&reatment of misse abortion #unlabele use$:

Sublingual( :** &cg; &ay re!eat e%ery hours 4or ) additional doses i4 needed5AC1, )**=a7'

/ntra%aginal( ** &cg; &ay re!eat e%ery hours 4or ) additional doses i4 needed5AC1, )**=a7'

Dosing( eriatric

Prevention of NSAID-inu!e gastri! ul!ers:Re4er to adult dosing'

Dosing( Renal /&!air&ent

Dose adust&ent is not routinely needed; ho$e%er, the dose &ay be reduced i4 thereco&&ended dose is not tolerated' /t is not #no$n i4 &iso!rostol is re&o%ed bydialysis'

Dosing( He!atic /&!air&ent

0o dosage adust&ent !ro%ided in &anu4acturerGs labeling'

Dosage For&s( 2'S'

E9ci!ient in4or&ation !resented $hen a%ailable 5li&ited, !articularly 4or generics7;consult s!eci4ic !roduct labeling'

Tablet, 1ral(

Cytotec( +** &cg


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Cytotec( )** &cg @scored

eneric( +** &cg, )** &cg

eneric Eui%alent A%ailable( 2'S'

Oes

Ad&inistration

/ncidence o4 diarrhea &ay be lessened by ha%ing !atient ta#e dose right a4ter &eals anda%oiding &agnesiu&-containing antacids' 8hen used 4or the !re%ention o4 0SA/D-induced ulcers, thera!y is usually begun on the second or third day o4 the ne9t nor&al&enstrual !eriod in $o&en o4 childbearing !otential'

2se

Bre%ention o4 0SA/D-induced gastric ulcers

Medical ter&ination o4 !regnancy o4 Z.= days in conunction $ith &i4e!ristone 5re4er toMi4e!ristone &onogra!h 4or details7

2se - 2nlabeled

Cer%ical ri!ening and labor induction 5e9ce!t in $o&en $ith !rior cesarean deli%ery or&aor uterine surgery7; !re%ention o4 !ost!artu& he&orrhage; treat&ent o4 !ost!artu&he&orrhage; treat&ent o4 inco&!lete or &issed abortion in $o&en [+) $ee#s gestation

Medication Sa4ety /ssuesSound-ali#eloo#-ali#e issues(

Cytotec\ &ay be con4used $ith Cyto9an

Miso!rostol &ay be con4used $ith &eto!rolol, &i4e!ristone

Ad%erse Reactions Signi4icant

]+*>( astrointestinal( Diarrhea, abdo&inal !ain

+> to +*>(

Central ner%ous syste&( Headache

astrointestinal( Consti!ation, dys!e!sia, 4latulence, nausea, %o&iting

[+> 5Li&ited to i&!ortant or li4e-threatening7( Abnor&al taste, abnor&al %ision,al#aline !hos!hatase increased, alo!ecia, ana!hyla9is, ane&ia, a&ylase increase,an9iety, arrhyth&ia, arterial thro&bosis, arthralgia, cardiac enzy&es increased,

chest !ain, chills, con4usion, CA, dea4ness, de!ression, dia!horesis, dizziness,dro$siness, dys!hagia, dys!nea, dysuria, ede&a, e!ista9is, ESR increased, 4atigue,


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4e%er, / bleeding, / in4la&&ation, gingi%itis, glycosuria, gout; gynecologicaldisorders, he&aturia, he!atobiliary 4unction abnor&al, hy!er-hy!otension,i&!otence, loss o4 libido, M/, &uscle cra&!s, &yalgia, neuro!athy, neurosis,nitrogen increased, !allor, !hlebitis, !olyuria, !ul&onary e&bolis&, !ur!ura, rash,re4lu9, rigors, sti44ness, synco!e, thirst, thro&bocyto!enia, tinnitus, uterine ru!ture,

$ea#ness, $eight changes

Contraindications

Hy!ersensiti%ity to !rostaglandins; !regnancy 5$hen used to reduce 0SA/D-inducedulcers7

8arningsBrecautions

Concerns related to adverse effects:

^ Aborti4acient( '()S) *o+e ,arning: Due to t%e abortifa!ient property oft%is mei!ation. patients must be /arne not to give t%is rug to ot%ers)

Disease-related concerns:

^ Cardio%ascular disease( 2se $ith caution in !atients $ith cardio%ascular disease'

^ Renal i&!air&ent( 2se $ith caution in !atients $ith renal i&!air&ent'

Special populations:

^ Elderly( 2se $ith caution in the elderly'

^ Bregnancy( Ad%erse e%ents ha%e been re!orted $hen used outside o4 current!roduct labeling 5cer%ical ri!ening, induction o4 labor, !ost!artu&he&orrhage7' 2terine tachysystole &ay occur and !rogress to uterine tetany;utero!lacental blood 4lo$ &ay be i&!aired and uterine ru!ture or a&niotic4luid e&bolis& &ay occur' The ris# o4 uterine ru!ture &ay be increased $ithad%anced gestational age, grand &ulti!arity, or !rior uterine surgery' 2terineacti%ity and 4etal status should be &onitored in a hos!ital setting' Miso!rostolshould not be used in situations $here uterotonic drugs are other$ise

contraindicated or ina!!ro!riate'

^ 8o&en o4 childbearing !otential( '()S) *o+e ,arning: (se of misoprostoluring pregnan!y may !ause abortion. birt% efe!ts. or premature birt%)

It is not to be use to reu!e NSAID-inu!e ul!ers in a /oman of

!%ilbearing potential unless s%e is !apable of !omplying /it% effe!tive

!ontra!eptive measures an is at %ig% ris0 of eveloping gastri! ul!ers

an1or t%eir !ompli!ations) /4 needed, the !atient &ust ha%e a negati%e!regnancy test $ithin ) $ee#s o4 starting thera!y, she &ust use e44ecti%econtrace!tion during treat&ent, and thera!y should begin on the second orthird day o4 ne9t nor&al &enstrual !eriod' 8o&en o4 childbearing !otential

ta#ing this 4or reducing the ris# o4 0SA/D-induced gastric ulcers should be


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gi%en oral and $ritten $arnings o4 the !otential ad%erse e%ents i4 !regnancyoccurs during treat&ent'

Other warnings/precautions:

^ A!!ro!riate use( 2lcers( For use only in !atients at high ris# o4 co&!lications4ro& gastric ulcers 5eg, the elderly or !atients $ith conco&itant diseases7 or

!atients at high ris# 4or de%elo!ing gastric ulcers 5eg, those $ith a history o4ulcers7 ta#ing 0SA/Ds' Miso!rostol &ust be ta#en during the duration o4

0SA/D thera!y' /t is not e44ecti%e in !re%enting duodenal ulcers in !atientsta#ing 0SA/Ds'

Metabolis&Trans!ort E44ects

0one #no$n'

Drug /nteractions

5For additional in4or&ation( Launch Le9i-/nteract_ Drug /nteractions Brogra&7

Antacids( May enhance the ad%erseto9ic e44ect o4 Miso!rostol' More s!eci4ically,conco&itant use $ith &agnesiu&-containing antacids &ay increase the ris# o4diarrhea' Manage&ent( A%oid conco&itant use o4 &iso!rostol and &agnesiu&-containing antacids' /n !atients reuiring antacid thera!y, e&!loy &agnesiu&-4ree

!re!arations' Monitor 4or increased ad%erse e44ects 5e'g', diarrhea, dehydration7'E+!eptions: Alu&inu& Hydro9ide; Calciu& Carbonate; Sodiu& icarbonate'Risk

D: Consider therapy modification

Carbetocin( Miso!rostol &ay enhance the thera!eutic e44ect o4 Carbetocin'Risk X:Avoid combination

19ytocin( Miso!rostol &ay enhance the thera!eutic e44ect o4 19ytocin' Manage&ent(The &anu4acturer o4 &iso!rostol reco&&ends a%oiding conco&itant use $itho9ytocin' Miso!rostol &ay aug&ent e44ects o4 o9ytocin, !articularly $hen gi%en$ithin . hours o4 o9ytocin initiation'Risk D: Consider therapy modification

Ethanol0utritionHerb /nteractions

Food( Miso!rostol !ea# seru& concentrations &ay be decreased i4 ta#en $ith 4ood 5notclinically signi4icant7'

Bregnancy Ris# Factor

` 5sho$ table7

Bregnancy /&!lications

Teratogenic e44ects $ere not obser%ed in ani&al re!roduction studies' Congenitalano&alies 4ollo$ing 4irst tri&ester e9!osure ha%e been re!orted, including s#ull de4ects,
http://www.uptodate.com/contents/drug-interactionhttp://www.uptodate.com/contents/image?imageKey=DRUG%2F50021&topicKey=DRUG_GEN%2F9657&source=see_linkhttp://www.uptodate.com/contents/drug-interactionhttp://www.uptodate.com/contents/image?imageKey=DRUG%2F50021&topicKey=DRUG_GEN%2F9657&source=see_link


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cranial ner%e !alsies, 4alcial &al4or&ations, and li&b de4ects' Miso!rostol &ay !roduceuterine contractions; 4etal death, uterine !er4oration, and abortion &ay occur' '()S)*o+e ,arning: (se of misoprostol uring pregnan!y may !ause abortion. birt%

efe!ts. or premature birt%) It is not to be use to reu!e NSAID-inu!e ul!ers in

a /oman of !%ilbearing potential unless s%e is !apable of !omplying /it% effe!tive

!ontra!eptive measures an is at %ig% ris0 of eveloping gastri! ul!ers an1or t%eir!ompli!ations)/4 needed, the !atient &ust ha%e a negati%e !regnancy test $ithin )$ee#s o4 starting thera!y, she &ust use e44ecti%e contrace!tion during treat&ent, andthera!y should begin on the second or third day o4 ne9t nor&al &enstrual !eriod'8ritten and %erbal $arnings concerning the hazards o4 &iso!rostol should be !ro%ided'

Miso!rostol is FDA a!!ro%ed 4or the &edical ter&ination o4 !regnancy o4 Z.= days inconunction $ith &i4e!ristone'

ecause &iso!rostol &ay induce or aug&ent uterine contractions, it has been used o44-label as a cer%ical-ri!ening agent 4or induction o4 labor in $o&en $ho ha%e not had a!rior cesarean deli%ery or &aor uterine surgery' Hy!ersti&ulation o4 the uterus, uterineru!ture, or ad%erse e%ents in the 4etus or &other &ay occur $ith this use'

Lactation

Enters breast &il#use caution

reast-Feeding Considerations

Miso!rostol acid 5the acti%e &etabolite o4 &iso!rostol7 has been detected in breast &il#'Concentrations 4ollo$ing a single oral dose $ere ?':-)*'= !g&L a4ter + hour anddecreased to [+ !g&L by < hours' Ad%erse e%ents ha%e not been re!orted in nursingin4ants 5F/1, )*+)7'

Dietary Considerations

Should be ta#en $ith 4ood'

Bricing( 2'S' 5Medi-S!an\7

&ablets5Cytotec 1ral7

+** &cg 5+**7( ))?')

)** &cg 5+**7( +


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Dis!laimer: The !ricing data !ro%ided re!resent a &edian A8B andor AA8B !rice4or the brand andor generic !roduct, res!ecti%ely' The !ricing data should be used 4or

bench&ar#ing !ur!oses only, and as such should not be used to set or adudicate any!rices 4or charging or rei&burse&ent 4unctions' Bricing data is u!dated &onthly'

Monitoring Bara&eters

Bre%ention o4 0SA/D-induced gastric ulcers( Bregnancy test in $o&en o4 re!roducti%e!otential !rior to thera!y; adeuate diagnostic &easures in all cases o4 undiagnosedabnor&al %aginal bleeding

144-label !regnancy-related uses( 2terine acti%ity and 4etal status' 8hen used 4orinco&!lete or &issed abortion, re-e%aluate +-) $ee#s a4ter dosing

/nternational rand 0a&es Alsoben 5B7;

Chro&alu9 5/D7; Cy!rostol 5AT7;

Cytil 5C17;

Cytolog 5/07;

Cytotec 5AE, AR, A2, E, F, , H, ", R, CH, C/, CL, C1, CR, CO, CP,

DE, D, EC, EE, E, ES, ET, F/, FR, , H, M, 0, R, H, H0, H2,/D, /E, /L, /, /R, /T, "1, "B, E, B, 8, L, LR, L2, LO, MA, ML, MR,MT, M2, M8, M`, MO, 0E, 0, 0/, 0L, 01, 0P, 1M, BA, BE, BL, BT, A,R2, SA, SC, SD, SE, S, S, SL, S0, S, SO, TH, T0, TR, T8, TP, 2, E,OE, PA, PM, P87;

astrul 5/D7; y&iso 5FR7;

/n%itec 5/D7;

Misel 5B7;

Misotrol 5C07;

0o!rostol 5/D7;

2-Miso 5T87

Mechanis& o4 Action

Miso!rostol is a synthetic !rostaglandin E+analog that re!laces the !rotecti%e

!rostaglandins consu&ed $ith !rostaglandin-inhibiting thera!ies 5eg, 0SA/Ds7; hasbeen sho$n to induce uterine contractions

Bhar&acodyna&icsinetics

Absor!tion( Ra!id and e9tensi%e

Metabolis&( He!atic; ra!idly de-esteri4ied to &iso!rostol acid 5acti%e7

Brotein binding( Miso!rostol acid( [=*>

Hal4-li4e eli&ination( Miso!rostol acid( )*-.* &inutes


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Ti&e to !ea#, seru&( Miso!rostol acid( Fasting( :-)) &inutes

E9cretion( 2rine 5*>7

Misoprostol as a single agent for mei!al termination of pregnan!y

Miso!rostol as a single agent 4or &edical ter&ination o4 !regnancyAuthors8esley Clar#, MD, MBHCaitlin Shannon, MBHe%erly 8ini#o44, MD, MBHSection EditorMi&i Pie&an, MDDe!uty EditorSandy " Fal#, MDDisclosuresAll to!ics are u!dated as ne$ e%idence beco&es a%ailable and our!eer re%ie$ !rocessis co&!lete'Literature re%ie$ current through( Se! )*+' This to!ic last u!dated( se! )*, )*+)'

/0TR1D2CT/10 3 Medical &ethods 4or induced abortion ha%e e&erged o%er the!ast t$o decades as sa4e, e44ecti%e, and 4easible alternati%es to surgery' 0onsurgicalalternati%es e9!and a $o&anGs treat&ent o!tions and, in turn, the uality o4 care @+'Moreo%er, in so&e settings, surgical o!tions are not a%ailable to $o&en or are not&edically 4easible'

/n 4irst tri&ester abortion, co&bined treat&ent $ith &iso!rostol$ith&i4e!ristonea!!ears to be &ore e44ecti%e than &iso!rostol-alone regi&ens, and thus,are considered the gold standard 4or &edical induction @)-.' Ho$e%er, &iso!rostol-alone regi&ens &ay be the treat&ent o4 choice in settings in $hich &i4e!ristone is nota%ailable or is too costly'

Miso!rostolis co&&only used as a single agent 4or second tri&ester induced abortionin the 2nited States and &any other !arts o4 the $orld @


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!otency o4 &iso!rostolGs e44ect, ho$e%er, %aries $ith gestational age, as $ell as $ithroute o4 ad&inistration, dose, dosing inter%al, and cu&ulati%e dose'

estational age 3 The sensiti%ity o4 the uterus to !rostaglandins increases $ith

gestational age @?' For this reason, !ro%iders generally use decreasing a&ounts

o4 &iso!rostol$ith increasing gestational age' Route o4 ad&inistration 3 Miso!rostolcan be ad&inistered by the 4ollo$ing

routes( %aginal, oral, sublingual, buccal, or rectal @-+' Seru& le%el 3 The !har&aco#inetic !ro4ile %aries by route @,=,+),+' 1ral or

sublingual ad&inistration leads to a ra!id !ea# in seru& le%el, $hich a!!ears todecrease in one to three hours' Con%ersely, $ith %aginal or buccal dosing, seru&le%els !ea# later and re&ain ele%ated longer @+),+'

2terine acti%ity 3 Regular and sustained uterine acti%ity is &ore li#ely

4ollo$ing %aginal, sublingual, or buccal co&!ared $ith oral ad&inistration @+' Moist %ersus dry tablets 3 Moistening o4 &iso!rostoltablets does not a!!ear to

increase clinical e44ecti%eness @+.-+?' A rando&ized trial e%aluated 4irst

tri&ester abortion using &ethotre9ate4ollo$ed by $et %ersus dry &iso!rostol;no di44erence $as 4ound bet$een the t$o grou!s @+.'

C10TRA/0D/CAT/10S

Absolute contraindications

Sus!ected or con4ir&ed ecto!ic !regnancy

estational tro!hoblastic disease

High ris# o4 uterine ru!ture 5ie, second or third tri&ester inductions in $o&en

$ith &ore than one !rior hysteroto&y, a !rior classical or T-sha!ed uterineincision, or e9tensi%e trans4undal uterine surgery7 /ntrauterine de%ice 5/2D; &ust be re&o%ed be4ore &iso!rostolis ad&inistered7

Allergy to !rostaglandins

Contraindications to &edical or surgical uterine e%acuations 5eg,

he&odyna&ically unstable, coagulo!athy7 5see 61%er%ie$ o4 !regnancyter&ination67'

Relati%e contraindications 3 Miso!rostol-alone regi&ens should be used $ith cautionin $o&en $ho are at ris# 4or co&!lications o4 !regnancy ter&ination 5eg,coagulo!athy7' Brecautions s!eci4ic to &iso!rostol are considered here' A 4ull

discussion o4 abortion co&!lications is !resented se!arately' 5See 61%er%ie$ o4!regnancy ter&ination6, section on GCo&!licationsG'7

Ris# 4actors 4or uterine ru!ture 3 2terine ru!ture is a ris# o4 &iso!rostoluse at anyti&e during !regnancy' 8hile the ris# is li#ely higher is $o&en $ith a uterine scar,there are 4e$ re!orts o4 this co&!lication 5table +7 @+' /n a syste&atic re%ie$ o4a%ailable studies, the ris# o4 ru!ture $as *' !ercent a&ong $o&en $ith a !riorcesarean deli%ery $ho $ere undergoing second tri&ester &iso!rostol-induced abortion@+=' Ad%anced gestational age, high gra%idity 5 !regnancies7 or uterine ano&alies&ay also increase ris# o4 ru!ture'

2terine ru!ture has only been re!orted once in $o&en undergoing 4irst tri&esterru!tures @)*'
http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/7http://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/8-13http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/8,9,12,13http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/12,13http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/13http://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/14-17http://www.uptodate.com/contents/methotrexate-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/14http://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/overview-of-pregnancy-termination?source=see_linkhttp://www.uptodate.com/contents/overview-of-pregnancy-termination?source=see_linkhttp://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/overview-of-pregnancy-termination?source=see_link&anchor=H24#H24http://www.uptodate.com/contents/overview-of-pregnancy-termination?source=see_link&anchor=H24#H24http://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/image?imageKey=OBGYN%2F58285&topicKey=OBGYN%2F5434&rank=5~110&source=see_link&search=misoprostol+and+missed+abortionhttp://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/18http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/19http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/20http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/7http://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/8-13http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/8,9,12,13http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/12,13http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/13http://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/14-17http://www.uptodate.com/contents/methotrexate-drug-information?source=see_linkhttp://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/14http://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/overview-of-pregnancy-termination?source=see_linkhttp://www.uptodate.com/contents/overview-of-pregnancy-termination?source=see_linkhttp://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/overview-of-pregnancy-termination?source=see_link&anchor=H24#H24http://www.uptodate.com/contents/overview-of-pregnancy-termination?source=see_link&anchor=H24#H24http://www.uptodate.com/contents/misoprostol-drug-information?source=see_linkhttp://www.uptodate.com/contents/image?imageKey=OBGYN%2F58285&topicKey=OBGYN%2F5434&rank=5~110&source=see_link&search=misoprostol+and+missed+abortionhttp://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/18http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/19http://www.uptodate.com/contents/misoprostol-as-a-single-agent-for-medical-termination-of-pregnancy/abstract/20


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/n the second tri&ester, uterine ru!ture is rare, but has been re!orted &ore 4reuentlythan in the 4irst tri&ester @)+-)=' Case re!orts o4 uterine ru!ture in $o&en undergoingsecond tri&ester abortion $ith &iso!rostolinclude $o&en $ith scarred @)+-): andunscarred uteri @):-)='

Scarred uterus 3 There are no high uality data regarding the ris# o4 uterineru!ture $ith use o4 &iso!rostol4or 4irst or second tri&ester !regnancyter&ination' A&ong 4i%e !ublished case series o4 $o&en $ith a !rior cesareansection $ho $ere undergoing second tri&ester &iso!rostol abortion 5n K


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and +? hours7 @: and &ay !rolong 5++ %ersus +. hours7 @? induction ti&e; one trial4ound an increase in the use o4 &or!hinein !atients treated $ith la&inaria @?' A 4ulldiscussion o4 cer%ical !re!aration 4or !regnancy ter&ination can be 4ound se!arately'5See 61%er%ie$ o4 !regnancy ter&ination6, section on GCer%ical !re!arationG'7

There is no high uality e%idence regarding the use o4 antibiotic !ro!hyla9is 4or &edicalabortion 5ie, no in%asi%e &ethods 4or cer%ical !re!aration or uterine e%acuation7'Ho$e%er, due to se%eral deaths due to clostridial se!sis in the 2nited States in !atients$ho recei%ed %aginal &iso!rostolin co&bination $ith &i4e!ristone, so&eorganizations, such as Blanned Barenthood 5the largest abortion !ro%ider in the 2nitedStates7, ha%e introduced the use o4 !ro!hylactic antibiotics @,=' Ho$e%er, deathsdue to clostridial in4ection ha%e been re!orted a&ong $o&en ad&inistering &iso!rostol

both %aginally and buccally @.*' 5See 6Mi4e!ristone 4or the &edical ter&ination o4!regnancy6'7

Bretreat&ent e%aluation 4or !regnancy ter&ination is discussed in detail se!arately' 5See

61%er%ie$ o4 !regnancy ter&ination6, section on GBreo!erati%e considerationsGand6Bre%ention o4 Rh5D7 alloi&&unization6'7

DATA 10 DR2 ADM/0/STRAT/10 3 The o!ti&al &iso!rostolregi&en at anygestational age is deter&ined by achie%ing a balance a&ong e44ecti%eness, ad%ersee44ects, and acce!tability to !atients' As an e9a&!le, higher doses and shorter dosinginter%als increase e44ecti%eness, but also &ay result in higher rates o4 ad%erse e44ectsand co&!lications @?'

Route o4 ad&inistration 3 E44ecti%eness 5de4ined as co&!lete abortion $ithout surgicalinter%ention7 is higher $ith %aginal co&!ared $ith oral ad&inistration in both 4irst andsecond tri&esters @.+-..' Ho$e%er, in a rando&ized trial, $o&en !re4erred oral ratherthan %aginal dosing @++'

Accu&ulating e%idence regarding sublingual ad&inistration a!!ears !ro&isingregarding e44ecti%eness and !atient acce!tability @.


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+) to < hours7 @:,.,..,:+' Ad%erse e44ects $ere si&ilar bet$een the t$oroutes, $ith the !ossible e9ce!tion o4 a higher incidence o4 4e%er $ith %aginaldosing @., and o4 nausea and diarrhea $ith oral dosing @:+' Findings onad%erse e44ects are not consistent and thus do not !ro%ide high uality e%idence4or guiding route o4 ad&inistration'

Sublingual %ersus %aginal dosing 3 /n !regnancies at +) $ee#s o4 gestation orless, data suggest that the sublingual route &ay be as e44ecti%e as the %aginalroute $hen dosed a!!ro!riately @.+,.


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Co&bined-route regi&ens 4or second tri&ester ter&inations 3 Regi&ens thatco&bine an initial %aginal &iso!rostoldose 4ollo$ed by oral doses ha%e beenco&&only used 4or ter&inations a4ter +) $ee#s and a!!ear to be as e44ecti%e as%aginal-only regi&ens @?,..,?


26/74

e44ecti%e than %aginal in this gestational age range' More research is needed todeter&ine $hether sublingual ad&inistration should be used a&ong $o&en $ithgestations + to )) $ee#s, and the a!!ro!riate regi&en 5seeGRoute o4ad&inistrationGabo%e7'

) to ): $ee#s 3 Many studies ha%e e9a&ined the use o4 &iso!rostol-alone

regi&ens beyond ) $ee#s o4 gestation, and data sho$ that the &ethod,e&!loying a %ariety o4 regi&ens, can be sa4ely and e44ecti%ely used in $o&en$ith ad%anced gestations @..,?


27/74

.** &cg B e%ery three to 4our hours 5&a9 4i%e doses7 @+ 1R

:** &cg B e%ery +) hours @)

) or &ore $ee#s 3 Treat&ent should be ad&inistered only in a clinic setting $ithi&&ediate access to e&ergency surgery and blood trans4usion' As noted abo%e, there is

no $ell-established regi&en 4or this gestational age range, ho$e%er, it &ay be !rudentto use a decreased dose 5)** to .** &cg7 or increased dosing inter%al 5si9 hours7' 1neo!tion is to gi%e .** &cg B e%ery si9 hours @)+,)) 5see GDose and dosing inter%alGabo%e7'

M10/T1R/0 D2R/0 TREATME0T 3 8o&en are &onitored during treat&ent$hether it occurs at ho&e or in a clinic setting' The goals o4 &onitoring are to assesstreat&ent e44icacy and assess 4or co&!lications'

At-ho&e treat&ent 3 A $o&an undergoing &edical ter&ination at ho&e should ha%eeasy access to a clinician $ho can ans$er uestions and &anage co&!lications

&edically or surgically' Batient education should include ho$ to recognizeco&!lications 5eg, 4e%er, abdo&inal !ain, or !rolonged or e9cessi%e bleeding7 5table )7'

/n addition, a $o&an should also call her !ro%ider i4 it does not see& that the treat&enthas been e44ecti%e' Ty!ically, i4 . hours ha%e !assed since co&!letion o4 treat&ent anda $o&an has not had bleeding greater than a &enstrual !eriod, it is li#ely that she &ayha%e an inco&!lete abortion or continuing !regnancy @=)'

/n-clinic treat&ent 3 E9a&ination o4 !resu&ed !roducts o4 conce!tion or !el%ice9a&ination are !er4or&ed be4ore each additional&iso!rostoldose is ad&inistered inorder to deter&ine $hether the 4etus has been e9!elled' The 4reuency and strength o4uterine contractions are also &onitored, and additional doses should be de4erred i4uterine contractions are strong 5strong to !al!ation or by !atient re!ort7 andor too4reuent 5] contractions+* &in7 @'

/n !regnancies at + $ee#s or greater, i4 a $o&an does not abort a4ter ). hours, theo!tion o4 a second course o4 &iso!rostoltreat&ent or surgical e%acuation can be o44ered@+,' There are insu44icient data on the sa4ety and e44ecti%eness o4 aug&entation $ithother uterotonics 5eg, !rostaglandins or o9ytocin7 @' As $ith &iso!rostol, i4additional uterotonics are used, !recautions should be ta#en to a%oid uterinehy!ersti&ulation, as it &ay lead to ru!ture'

E9!ulsion o4 the !lacenta should be con4ir&ed' E9!ulsion usually occurs shortly a4terthe 4etus is deli%ered' A4ter e9!ulsion, the !lacenta should be e9a&ined to see $hether itis co&!lete'

Ad%ice regarding ti&e inter%al to $ait 4or !lacental e9!ulsion %aries 4ro& * &inutes to4our hours; in a retros!ecti%e study, there $as no &orbidity associated $ith a $aiting

!eriod o4 4our hours @=' /4 t$o or &ore hours ha%e !assed and the !lacenta has notdeli%ered, an in4usion o4 o9ytocin+* units in


28/74

e4ore discharge 4ro& the clinic, clinicians should obser%e $o&en 4or at least 4ourhours to &onitor %ital signs and obser%e 4or se%ere abdo&inal !ain or e9cessi%e %aginal

bleeding'

/4 . hours ha%e !assed and abortion is not co&!lete, surgical e%acuation is ty!ically

!er4or&ed @'

F1LL18-2B 3 A4ter treat&ent, $o&en should be educated about ho$ to recognizeco&!lications 5eg, 4e%er, abdo&inal !ain, or !rolonged or e9cessi%e bleeding7 5table )7'A 4ollo$-u! %isit is conducted at one to t$o $ee#s !ost-treat&ent' A thorough clinicalhistory and bi&anual !el%ic e9a&ination is !er4or&ed to e%aluate uterine size, bleeding,and assess 4or in4ection'

The &ost i&!ortant uestions to as# at the 4ollo$-u! %isit are(

Do you 4eel !regnant

Did you see the e9!ulsion o4 the gestational sac or 4etus Ho$ &uch bleeding did you ha%e

Are you still bleeding

These uestions and a !el%ic e9a&ination to deter&ine uterine size are su44icient todetect &ost $o&en in need o4 4urther treat&ent 4or inco&!lete abortion 5retained

!roducts o4 conce!tion, no or inconsistent uterine gro$th, and lac# o4 cardiac acti%ityon ultrasound7 or ongoing !regnancy 5uterine gro$th consistent $ith the ti&e ela!sed

bet$een the 4irst and 4ollo$-u! %isits and cardiac acti%ity on %aginal ultrasound7'

/4 there is uncertainty about $hether there is an inco&!lete abortion 5retained !roductso4 conce!tion, no or inconsistent uterine gro$th, and lac# o4 cardiac acti%ity onultrasound7 or ongoing !regnancy 5uterine gro$th consistent $ith the ti&e ela!sed

bet$een the 4irst and 4ollo$-u! %isits and cardiac acti%ity on %aginal ultrasound7, a%aginal ultrasound e9a&ination &ay be necessary' enerally s!ea#ing, a seru& hC isonly used $hen there is concern about non-uterine !regnancy andor $hen ultrasound isnot a%ailable'

8hile hC concentration &ay re&ain ele%ated 4or $ee#s a4ter co&!lete abortion, a&easure&ent that 4alls to less than )* !ercent o4 its !re-!rocedure %alue generallyindicates success4ul !regnancy ter&ination @=.' Also, there is no consensus regarding

the u!!er li&it o4 endo&etrial thic#ness associated $ith a success4ul &edical abortion;there4ore, it is not a good diagnostic tool 4or deter&ining $hether 4urther inter%ention&ay be reuired @=


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E44ecti%eness 5de4ined as co&!lete abortion7 o4 &iso!rostolalone 4or !regnancyter&ination is as 4ollo$s'

Z= $ee#s 5$ee#s o4 a&enorrhea7( ?< to < !ercent @:),?

+* to +) $ee#s( * to < !ercent @?

+ $ee#s( * to =* !ercent @

ADERSE EFFECTS 3Miso!rostolis a sa4e and $ell-tolerated &edication @+*)'astrointestinal sy&!to&s 5nausea, diarrhea7 and 4e%er are the &ost co&&on ad%ersee44ects o4 &iso!rostol' These are generally transient and sel4-li&iting'

astrointestinal sy&!to&s 3 Diarrhea is the &aor ad%erse reaction that has beenre!orted consistently, but it is usually &ild and sel4-li&iting' 0ausea and %o&iting &ayalso occur @+*)' The &aority o4 cases can be &anaged e9!ectantly or $ith anti-e&eticor anti-diarrheal &edication'

These sy&!to&s ha%e been obser%ed $ith all 4our routes o4 ad&inistration; se%erity&ay be dose and inter%al de!endent 5ie, higher doses and shorter dosing inter%als &aylead to increased sy&!to&s7 @:),?,+**,+*'

Fe%er 3 Fe%er, e%en in the absence o4 in4ection is a co&&on e44ect o4&iso!rostol,re!orted in < to !ercent o4 !atients undergoing 4irst tri&ester abortion @?,


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First tri&ester 3 For $o&en undergoing 4irst tri&ester inductions, &anage&ent o4ongoing !regnancy 5cardiac acti%ity on ultrasound7 or inco&!lete abortion 5sac or othere%idence o4 !roducts o4 conce!tion, but no gestational gro$th and no cardiac acti%ity onultrasound7 are generally di44erent' 8e assess $o&en at the 4ollo$-u! %isit 5one to t$o$ee#s7 and ad%ise surgery 4or all ongoing !regnancies' For inco&!lete abortion, $e

ad%ise e9!ectant &anage&ent or a second dose o4&iso!rostol'For $o&en $ho recei%ea second dose, $e schedule a second 4ollo$-u! assess&ent at one to t$o $ee#s'

8e generally donGt gi%e &ore than one additional dose' This is because the cu&ulati%ebene4it o4 additional doses is not established and reuiring &ulti!le 4ollo$-u! %isitsincreases the chance o4 loss-to-4ollo$-u!'

Second tri&ester 3 For $o&en in second tri&ester, &anage&ent o4 retained !roductso4 conce!tion 5B1Cs7 de!ends on the !oint in the !rocess at $hich they are sus!ected ordiagnosed'

A4ter 4etal e9!ulsion and be4ore discharge 4ro& the hos!ital or clinic, clinicians shouldcon4ir& that the 4etus and !lacenta ha%e been co&!letely e9!elled'

Many clinicians &anage retained !roducts o4 conce!tion 5B1Cs7 $ith surgicale%acuation' Clinicians can choose either dilatation and curettage or &anual %acuu&as!iration, de!ending on the clinical situation' 5See 6Surgical ter&ination o4 !regnancy(First tri&ester6and 6Ter&ination o4 !regnancy( Second tri&ester6'7

Ho$e%er, so&e clinicians treat retained B1Cs a4ter a second tri&ester induction $ith anadditional dose or t$o o4 &iso!rostol' The e44icacy o4 this !ractice has not beenestablished in the literature, but a%oiding surgical inter%ention is al$ays reco&&ended,and there are no #no$n dangers o4 gi%ing additional &iso!rostol doses a4ter 4etale9!ulsion'

/t is rare 4or retained B1Cs to be detected only a4ter discharge 4ro& the clinic, and thereis no standard a!!roach' Manage&ent 5e9!ectant &anage&ent, additional&iso!rostol,or surgery7 should be tailored to the !atientGs !re4erences and the clinical situation'

2terine ru!ture 3 Miso!rostol, and other agents $hich sti&ulate uterine contractions5eg,o9ytocin, other !rostaglandins7, &ay increase ris# o4 dehiscence or a !rior uterinescar or uterine ru!ture' 5See GRis# 4actors 4or uterine ru!tureGabo%e'7

Bre!rocedure screening o4 !atients 4or ris# 4actors and close obser%ation duringtreat&ent are crucial to !re%ent or detect early signs o4 uterine ru!ture' /n addition, the&ini&u& cu&ulati%e &iso!rostoldose should be used 5ie, lo$est dose, longest dosinginter%al, lo$est nu&ber or total doses7'

Clinical &ani4estations o4 uterine ru!ture 4ollo$ing &edical ter&ination o4 !regnancyare %ariable' /n $o&en $ith #no$n uterine scarring, uterine ru!ture should al$ays bestrongly considered i4 se%ere and !ersistent abdo&inal !ain andor signs o4intraabdo&inal he&orrhage are !resent' aginal bleeding is not a cardinal sy&!to&, asit &ay be &odest, des!ite &aor intraabdo&inal he&orrhage' 1ther clinical

&ani4estations include hy!otension ranging 4ro& subtle to se%ere 5hy!o%ole&ic shoc#7,cessation o4 uterine contractions, and uterine tenderness' He&aturia &ay occur i4 the
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ru!ture e9tends to the bladder' /n a stable !atient, ultrasound e9a&ination &ay con4ir&the diagnosis @),++' 5See 6Choosing the route o4 deli%ery a4ter cesarean birth6,section on G/na!!ro!riate candidatesG'7

Ru!ture or dehiscence is &anaged $ith e9!loratory la!aroto&y, $ith either uterine

re!air or hysterecto&y' Conser%ati%e surgery also reuires co&!letion o4 the !regnancyter&ination'

Teratogenicity 3 uestions regarding the teratogenicity o4&iso!rostol&ay arise incases $here co&!lete abortion is not achie%ed a4ter one or &ore doses and a $o&andoes not 4ollo$-u! or chooses to continue a !regnancy' The teratogenic ris# o4&iso!rostol a!!ears to be lo$ and generally li&ited to 4irst tri&ester e9!osure,according to a re%ie$ o4 case re!orts @++.' Des!ite the lo$ ris#, $o&en $ho do notabort a4ter induction $ith &iso!rostol should be counseled about the ris# o4 4etal&al4or&ation'

The &echanis& 4or &iso!rostol-associated 4etal &al4or&ations a!!ears to be %asculardisru!tion, !ossibly due to alteration o4 4etal blood 4lo$ due to uterine contractions@,++.-++?'

M/S1BR1ST1L-AL10E C1MBARED T1 1THER RE/ME0S

Miso!rostol %ersus other !rostaglandins 3 Co&!ared $ith other !rostaglandins,&iso!rostolhas less ad%erse e44ects, is orally acti%e, te&!erature stable, less e9!ensi%e,and $idely a%ailable, including( BE) 5dino!rostone7 and BF)al!ha 5carbo!rost7@++'

/n a syste&atic re%ie$ o4 rando&ized trials in $o&en undergoing !regnancyter&ination in the second or third tri&ester, %aginal &iso!rostolco&!ared $ithge&e!rost 5another BE+7 $as associated $ith reduced narcotic analgesia 5RR *':.,= C/ *'.=J*'.7 and surgical e%acuation o4 the uterus 5RR *'?+, = C/ *'


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is &ore cu&berso&e to use than &i4e!ristoneand &iso!rostol and &iso!rostol alone'Also, it can only be used sa4ely through se%en $ee#s o4 gestation'

/0F1RMAT/10 F1R BAT/E0TS 3 2!ToDate o44ers t$o ty!es o4 !atient education&aterials, The asicsN and eyond the asics'N The asics !atient education !ieces

are $ritten in !lain language, at the