First-Trimester Medication Abortion (Termination of Pregnancy)

10/27/2017 First-trimester medication abortion (termination of pregnancy) - UpToDate
Official reprint from UpToDate®

www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
First-trimester medication abortion (termination of pregnancy)
Author: Bryna Harwood, MD, MS

Section Editor: Jody Steinauer, MD, MAS
Deputy Editor: Sandy J Falk, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2017. | This topic last updated: Aug 29, 2016.
INTRODUCTION — Medication abortion (also referred to as medical abortion) is the termination of pregnancy
with use of medications alone rather than surgery. Mifepristone, an antiprogestin, is approved for use in the
United States, in combination with misoprostol, for the termination of pregnancies up to 70 days of gestation.
First-trimester medication abortion beyond 70 days is associated with a lower efficacy and requires in-hospital
supervision.
The use of mifepristone in combination with misoprostol for medication termination of pregnancy in the first
trimester is reviewed here. Use of misoprostol alone for medication abortion and other methods of pregnancy
termination are discussed separately. (See "Misoprostol as a single agent for medical termination of pregnancy"
and "Overview of pregnancy termination".)
MEDICATION VERSUS SURGICAL TERMINATION — Medication and surgical (uterine dilation and suction
aspiration) abortion are both safe and effective approaches for appropriately selected patients [1]. The choice is
based upon availability, gestational age (medication abortion is less successful in the late first trimester), and
patient preference. Women seeking abortion care should be counseled about the advantages and disadvantages
of both options.
Prior to 2000, Medication abortion in the first trimester was available only using a prostaglandin with or without
methotrexate. Since 2000, medication abortion with mifepristone and misoprostol was approved for use by the
US Food and Drug Administration (FDA) in the United States. Surgical abortion is still performed in the majority
of cases and also in cases in which medication abortion is incomplete. The United States Centers for Disease
Control and Prevention (CDC) reported that, in 2009, 16.2 percent of abortions at ≤8 weeks of gestation and 0.9
percent at >8 weeks were performed with medication alone [2].
First-trimester surgical abortion is effective in terminating pregnancy in 98 to 99 percent of procedures and has a
complication rate of 0 to 3 percent [3]. The major complications of surgical abortion are incomplete evacuation,
uterine perforation, problems related to anesthesia, and endometritis. (See "Surgical termination of pregnancy:
First trimester".)
The overall success rate of medication abortion with mifepristone and misoprostol is not quite as high as its
surgical counterpart; surgical aspiration to complete the termination is required in 2 to 8 percent of cases [4,5].
Incomplete evacuation is considered failure of the method rather than a complication.
In terms of complications, data from Planned Parenthood affiliates in 2009 to 2010 that included 233,805
medication abortions showed significant adverse events or outcomes occurred in 0.65 percent of women [6]. The
complication rate for medication abortion is similar to surgical abortion, but the types and etiologies of the
https://www.uptodate.com/contents/first-trimester-medication-abortion-termination-of-pregnancy/print?source=search_result&search=termination%20… 1/32
complications are different. Endometritis has a similar incidence as in surgical abortion; life-threatening infections
are rare, but have occurred more often than with surgical abortion. Hemorrhage occurs at similar rates, but the
cause is typically uterine atony or retained products of conception rather than the causes in surgical abortion,
which are usually cervical laceration or uterine injury due to instrumentation. (See 'Side effects and
complications' below.)
The teratogenic risk to an ongoing pregnancy is higher with medication abortion than with surgical abortion, but
ongoing pregnancy is rare. (See 'Teratogenicity' below.)
The main difference between surgical and medication abortion is the patient’s experience. The surgical
procedure is completed in one office visit and takes place in a healthcare facility. Patients experience a
gynecologic procedure in the lithotomy position and then leave the visit knowing that the abortion is complete.
Analgesics or anesthesia may be used, but there may be some discomfort during the procedure and mild to
moderate uterine cramping and bleeding for several days afterward.
Medication abortion avoids a surgical procedure and anesthesia, but takes a longer time (several days) and at
least one more clinic visit than a surgical abortion. The patient usually experiences more uncomfortable effects
and over a longer period of time (bleeding, cramping, nausea, vomiting). The patient has a greater awareness of
the blood loss and may be able to identify pregnancy tissue that passes. Some patients prefer the greater degree
of control they have over the process and having part of the process in a nonclinical setting [7]. In addition, some
patients will require a surgical abortion if the medication abortion is unsuccessful. If the patient has an ongoing
pregnancy, there is a risk of fetal abnormalities. (See 'Teratogenicity' below.)
Acceptability is high for both medication and surgical abortion, but satisfaction appears to be higher after surgical
abortion. This was illustrated in two randomized trials that found that the rate of patient satisfaction was
significantly higher for surgical abortion (92 verus 82 percent in one trial [8]; 94 versus 69 percent in another [7]).
In contrast, in a prospective cohort study, a higher proportion of women who underwent medication abortion
would choose the same method if a future abortion was required (81 versus 58 percent in the surgical abortion
group) [9].
Given the available data, we suggest first-trimester medication abortion for eligible women who place a high
value on avoiding surgery or anesthesia and who are willing to accept more discomfort and awareness of the
procedure. For other women, particularly those who place a high value on completing the procedure in one visit,
we recommend surgical abortion.
INDICATIONS — The US Food and Drug Administration has approved mifepristone for termination of
intrauterine pregnancy up to 70 days of gestation [10].
According to the manufacturer of mifepristone, pregnancy is dated from the first day of the last menstrual period
in a presumed 28-day cycle with ovulation occurring at mid-cycle [11]. The duration of pregnancy may be
determined from menstrual history and by clinical examination. Ultrasonographic scan should be used if the
duration of pregnancy is uncertain, or if ectopic pregnancy is suspected. Use beyond this gestational age is off-
label (see 'After 49 days of gestation' below).
The alternative to medication termination is surgical termination of pregnancy. The advantages and
disadvantages of each approach are discussed above. (See 'Medication versus surgical termination' above.)
CONTRAINDICATIONS — The manufacturer's list of contraindications to the use of mifepristone and

prostaglandins for medication abortion is listed in the table (table 1).
Medical conditions — Mifepristone is a glucocorticoid receptor antagonist and is therefore contraindicated in

patients with chronic adrenal failure or who are on concurrent long-term corticosteroid therapy.
Mifepristone should not be used by women with hemorrhagic disorders or who are on anticoagulant therapy or
medications that interfere with hemostasis, since this may lead to excessive bleeding during pregnancy
termination.
Mifepristone is porphyrinogenic and is contraindicated in women with porphyrias [12]. (See "Pathogenesis,
clinical manifestations, and diagnosis of acute intermittent porphyria", section on 'Medications'.)
Asthma is not a contraindication to use of misoprostol. Although some prostaglandins result in

bronchoconstriction, this effect has not been found with prostaglandin E1 (misoprostol). (See "Management of
asthma during pregnancy", section on 'Peripartum care'.)
Drug interactions — There are no data regarding safety and efficacy of mifepristone medication abortion for
women with chronic medical conditions (eg, hypertension, diabetes, cardiovascular, respiratory, hepatic, or renal
disease) or who are cigarette smokers. Therefore, the labeling of mifepristone for medication abortion advises
caution in women with these conditions. If medical conditions are well controlled, medication abortion can be
provided safely, but clinical judgment must be used regarding the individual’s risks and alternatives. For medical
conditions that are poorly controlled and in which there is clinical concern for excessive blood loss or a need for
monitoring, surgical abortion under controlled conditions is generally preferable.
Drug interactions with mifepristone should be investigated for patients who are on other medications.
Mifepristone is metabolized by cytochrome P450 3A4 (CYP3A4), and thus may theoretically interact with agents
that impact CYP3A4 function (table 2). However, specific drug or food interactions with the single dose of
mifepristone used for pregnancy termination have not been reported. Even if interactions were shown to alter
serum concentrations, those concentrations are not correlated with efficacy and ingestion of a single dose in the
range of 200 mg up to 800 mg produces approximately the same serum concentration [13-15].
Mifepristone itself acts as a moderate inhibitor of CYP3A4 metabolism and can thereby alter concentrations of
other drugs. Due to its prolonged half-life and irreversible CYP binding, potential interactions of mifepristone
should be checked particularly for medications that have a narrow therapeutic index. Examples include:
immunosuppressants (eg, cyclosporine, sirolimus, tacrolimus); cardiovascular drugs (eg, calcium channel
blockers, anti-arrhythmics, others); analgesic/anesthetic agents (eg, fentanyl, ketamine, methadone, others). The
effect of a single dose of mifepristone on metabolism and effect of other drugs highly dependent upon CYP3A4
for their metabolism or activation may persist for up to two weeks. Interactions with these medications should be
checked prior to administration of mifepristone.
Some medications that inhibit CYP3A4 metabolism are associated with QT interval prolongation (table 3) [16].
There are no reported cases of QT prolongation with use of mifepristone. The manufacturer of mifepristone
advises that use of the medication should be avoided with QT interval-prolonging drugs or in patients with
potassium channel variants resulting in a long QT interval [17]. (See "Acquired long QT syndrome".)
CLINICIAN REQUIREMENTS — The US Food and Drug Administration (FDA) requires that mifepristone be
prescribed only by physicians (not nurse practitioners, physician assistants, or nurse midwives) who are able to
[18]:
● Make an accurate assessment of gestational age
● Diagnose ectopic pregnancy
● Provide surgical intervention in cases of severe bleeding or incomplete abortion or make provisions to
provide such care through another provider
● Assure patient access to medical facilities equipped to perform blood transfusions and resuscitation.
These physicians:
● Must sign a prescriber's agreement with the manufacturer of mifepristone
● Require that patients read the manufacturer's Medication Guide and sign the Patient Agreement form
● Report any ongoing pregnancy or other serious events (eg, hospitalization, infection, blood transfusion).
The necessary forms and medication guide are available online from the manufacturer.
In most European countries, as in the United States, only physicians are allowed to prescribe mifepristone.
However, a physician may delegate another health professional to administer the drug, but the physician should
be on the premises.
MEDICATION REGIMEN — Initially, there were two commonly used regimens for first trimester medication
abortion. The original US Food and Drug Administration (FDA)/manufacturer-recommended regimen was issued
in 2000. It was mifepristone (600 mg orally), followed 48 hours later by misoprostol (400 mcg orally). Both
medications were to be administered by a clinician.
In addition, there was another protocol referred to as the evidence-based regimen. It is mifepristone (200 mg
orally) administered by a clinician, followed 24 to 72 hours later by misoprostol (800 mcg buccally) administered
either by a clinician or self-administered in a nonclinical setting, typically the patient's home.
However, in 2016, the FDA revised the labeling with a protocol that is nearly identical to the evidence-based
regimen [10,19]. The FDA-approved regimen is:
● Day one – 200 mg of mifepristone taken by mouth
● Twenty-four to 48 hours after taking mifepristone – 800 mcg of misoprostol taken buccally (in the cheek
pouch); this is taken at a location appropriate for the patient (clinic, home, or other location)
● Seven to 14 days after taking mifepristone – Follow-up with a clinician
Evidence for the regimen — The evidence-based regimen resulted in fewer ongoing pregnancies, a lower
frequency of side effects, lower cost, greater convenience, and greater efficacy at gestations between 50 and 63
days compared with the original FDA regimen.
Studies have evaluated the components of each regimen. This evidence is reviewed in the sections that follow.
Mifepristone — The oral mifepristone dose is 200 mg rather than 600 mg because it is as effective. This was
demonstrated in a meta-analysis of four randomized trials that found a comparable complete abortion rate for
600 mg compared with 200 mg (risk ratio 1.07; 95% CI 0.87-1.32) [20]. Use of a lower dose has the benefit of
decreasing the cost of the procedure.
Mifepristone is supplied in 200 mg tablets and use of doses lower than 200 mg do not offer a benefit and may be
less effective [21-23].
Mifepristone administered alone results in complete termination of pregnancy in 64 to 85 percent of women at

this gestational age [24-26]. Since these efficacy rates are inadequate for general clinical use, a prostaglandin is
administered after mifepristone.
Misoprostol — Misoprostol, a synthetic prostaglandin E1, is used sequentially with mifepristone for first-
trimester medication abortion. The drug is inexpensive, can be stored at room temperature, and is widely
available. Misoprostol is the sole prostaglandin approved by the FDA for use for medication abortion, and the
FDA requires misoprostol be used in conjunction with mifepristone for medication abortion.
Other prostaglandins have been used in combination with mifepristone for termination of pregnancy, but are
inferior to misoprostol. Gemeprost is supplied as a vaginal pessary. Gemeprost is expensive, needs to be
refrigerated, and is not registered for use in the United States. It has also been found in a randomized trial to be
associated with more treatment failures than misoprostol [27]. Another prostaglandin, sulprostone, was
associated with cardiovascular adverse effects [28].
Route of administration and dose — Misoprostol is manufactured and approved by the FDA for use as
an oral tablet, but several routes of administration (oral, vaginal, buccal, sublingual) have been used for
mifepristone/misoprostol first-trimester medication abortion. The dose ranges from 400 to 800 mcg and depends
upon the route.
We recommend buccal administration of misoprostol rather than other routes. Oral administration of misoprostol
is a reasonable option for women at ≤49 days of gestation. We recommend caution with the vaginal
administration of misoprostol due to a possible association with severe infection.
Buccal and vaginal dosing have greater bioavailability, a later peak serum concentration, and a longer duration of
bioactivity than oral administration [29-32]. These pharmacokinetics are likely responsible for the decrease in
side effects with vaginal dosing [1,20]. Vaginal and buccal administration is more effective than oral, particularly
for gestations of >49 days.
Vaginal administration was the original route used in the evidence-based regimen, but use of this route was
proposed as a contributing factor in rare cases of clostridial sepsis and death in women undergoing medication
abortion [33,34]. In addition, women have reported a preference for oral rather than vaginal administration in
some studies [35,36], but appear to find both oral and buccal dosing acceptable [37]. In response, buccal dosing
has become the preferred route. Sublingual administration is under investigation and is not commonly used
clinically. (See 'Clostridial sepsis' below.)
There are few high quality data comparing buccal and oral dosing. In the only randomized trial, buccal dosing
was more effective than oral, but a subgroup analysis found a significant decrease in the rate of failure to
achieve complete abortion only for >49 days (5 versus 13 percent; risk ratio 0.37, 95% CI 0.18-0.73) and
insufficient statistical power to assess the difference at ≤49 days (3 versus 4 percent; risk ratio 0.72, 95% CI
0.25-2.04) [37]. The rate of gastrointestinal side effects and patient satisfaction were similar for the two routes of
administration.
Most trials have compared vaginal and oral dosing, since the vaginal route was the original route of
administration used for the evidence-based regimen. Randomized trial data have shown that the vaginal route is
more effective and is associated with fewer side effects than oral dosing, which is used in the FDA/manufacturer
regimen [38]. A meta-analysis of four randomized trials found that oral compared with vaginal dosing resulted in
a significantly higher rate of failure to achieve complete abortion (11 versus 4 percent; risk ratio 3.05, 95% CI
2.24-4.14) and side effects, including nausea and diarrhea [20].
Buccal and vaginal administration were found to have similar efficacy and incidence of side effects in one
randomized trial, but this provides only indirect support for comparing buccal with oral dosing [39]. In addition,
women reported a preference for oral rather than vaginal administration in some studies [35,36].
The buccal misoprostol dose used in the evidence-based and revised FDA regimen is 800 mcg; however, 400
mcg was found to be equally effective in a randomized trial [40]. For buccal dosing, the patient places the tablets
of misoprostol between the cheek and gum of the lower jaw where the tablets remain for at least 30 minutes.
Typically patients are instructed to swallow any remaining pill fragments after 30 minutes.
Sublingual administration is under investigation, but the disadvantage of this route is that it has a similar
pharmacokinetic profile to oral dosing. One randomized trial found comparable efficacy and side effects for
sublingual and buccal administration [41].
The addition of a second dose of misoprostol after three to four hours has been proposed. Studies show that this
increases side effects, but may decrease the rate of ongoing pregnancy, especially at later gestational ages [42-
44]. Additional doses of misoprostol are not currently part of either the FDA-approved regimen or the evidence-
based alternative regimen.
Timing — The interval from mifepristone to misoprostol is 24 to 48 hours in the FDA/manufacturer regimen
and 24 to 72 hours in the evidence-based regimen. Extending the interval to 24 to 72 hours does not appear to
impact efficacy.
This flexibility in dosing increases convenience for women, since they can schedule their abortion accordingly
when time permits and a support person is available. Studies have consistently supported similar efficacy for
buccal administration of misoprostol 24 to 48 hours after mifepristone with success rates of 95 to 98 percent
[39,45].
Most studies evaluating the effect of varying intervals on efficacy evaluated vaginal or buccal dosing of the
misoprostol. A meta-analysis of randomized trials included three trials for which the summary data showed no
significant difference in the rate of complete abortion when the interval was decreased from 48 to 24 hours (risk
ratio 1.24, 95% CI 0.95-1.63) [20]. One trial showed no difference in efficacy for an interval of 72 compared with
48 hours (risk ratio 1.68, 95% CI 0.95-3.01), but this trial lacked sufficient statistical power to detect a difference
[46]. In the same trial, 72 compared with 24 hours resulted in a significant increase in the rate of incomplete
abortion (4 versus 2 percent; risk ratio 1.93, 95%CI 1.05-3.58). Most comparisons in the meta-analysis showed
no difference in side effects with a variation in interval from 24 to 72 hours.
Intervals from mifepristone to misoprostol of less than 24 hours appear to be less effective [20,47]. There are no
data on misoprostol administration more than 72 hours after mifepristone.
Clinician versus self-administration — The revised FDA and the evidence-based regimen includes self-
administration of misoprostol at home rather than by a clinician in a clinic setting. This approach appears to be as
safe and effective as administration in a clinic setting, and offers advantages in terms of cost and convenience.
This was best illustrated in a systematic review of 9 prospective studies including 4522 women undergoing first-
trimester medication abortion that found that self-administration at home compared with administration by a
clinician was associated with no significant differences in the rate of complete abortion (86 to 97 percent versus
80 to 99 percent; odds ratio 0.8, 95% CI 0.5-1.5) [48]. Self-administration was associated with higher patient
satisfaction. There was a slight increase in the duration of pain and vomiting (0.3 days longer) with self-
administration, but no increase in contact with health services.
CLINICAL PROTOCOL — First-trimester medication abortion typically includes the following steps:
● Initial visit and mifepristone administration – The patient is seen in an outpatient setting. This visit
includes confirmation of pregnancy, counseling about options and informed consent, blood typing and
administration of Rh immune globulin if needed. A single dose of mifepristone is administered.
● Misoprostol administration – Misoprostol is self-administered by the patient in a nonclinical setting 24 to 72

hours after mifepristone administration.
● Follow-up visit – A final visit is conducted within two weeks after treatment to ensure that the pregnancy
was completely expelled, to identify any complications requiring treatment, and to provide contraception.
Initial clinic visit — The first clinic visit is used to assess a woman's eligibility for medication abortion and to
dispense mifepristone.
Preprocedure evaluation and preparation
Pregnancy confirmation and gestational age — Pregnancy should be confirmed by urinary or serum
human chorionic gonadotropin (hCG) measurement or pelvic ultrasound.
Gestational age must be assessed by clinical evaluation or ultrasound because the duration of gestation is
critical to deciding whether a woman is a candidate for medication termination of pregnancy. (See 'Indications'
above and "Overview of pregnancy termination", section on 'Determining gestational age'.)
Sonographic evaluation also allows exclusion of ectopic pregnancy. For women with symptoms or high risk
factors, ectopic pregnancy should be excluded before proceeding with mifepristone administration. Mifepristone
is not an effective treatment for extrauterine gestations. (See "Ectopic pregnancy: Incidence, risk factors, and
pathology" and "Ectopic pregnancy: Clinical manifestations and diagnosis".)
Screening of asymptomatic women for chlamydia and/or gonorrhea should be done based on appropriate
guidelines for the general population. (See "Screening for sexually transmitted infections", section on 'Females'.)
Counseling and informed consent — Women considering medication abortion should be counseled
about other options and the details of the procedure. The steps of the procedure should be reviewed and the
patient should confirm that she is willing and able to complete each step and to contact the clinician if she has
questions or concerns during the process. Comprehensive counseling about the expected experience and
symptoms and recovery is especially important with medication abortion, as the patient is deciding between
options with very different expected experiences (surgical abortion, medication abortion, continuation of
pregnancy). In addition, the patient should be counseled that a surgical procedure will be required to complete
the procedure if it is unsuccessful and that an ongoing pregnancy will have the risk of fetal abnormalities. (See
'Incomplete abortion or ongoing pregnancy' below.)
The patient should be given the Medication Guide and Patient Agreement to review and discuss with her
provider. These forms are available from the manufacturer. Informed consent should be documented in the
medical record and on the procedure consent form.
Alloimmunization prevention and other issues — Rh typing should be performed and Rh negative
women should receive anti-D immune globulin [1]. (See "Prevention of Rhesus (D) alloimmunization in
pregnancy".)
If the woman has an intrauterine device in place, it should be removed.
Legal requirements regarding pregnancy termination and age limits, parental consent, and preprocedure
counseling vary by state in the United States. Information regarding these requirements is provided by the state
government or on the Guttmacher Institute website.
Mifepristone — The woman is given mifepristone if she meets eligibility criteria (table 4) and after she
consents to the procedure. Occasionally, patients will experience bleeding or cramping after the mifepristone
dose. Most women only have symptoms after the misoprostol, especially if it is given within 24 to 36 hours of
mifepristone. However, even if bleeding and cramping occurs, unless expulsion of the gestation has been
confirmed, patients should take the misoprostol as instructed. Approximately 1 to 5 percent of patients will expel
the conceptus after a single dose of mifepristone only, without misoprostol [49].
Prophylactic antibiotics — Use of prophylactic antibiotics for medication abortion is controversial [50]. The
rate of infection following medication abortion is low, approximately 0.3 percent in prospective studies
[28,30,49,51-53]. However, some cases of serious infection do occur. In particular, there have been rare cases of
sepsis and death in women with clostridial infections. A possible contributing factor to these infections was use of
a vaginal route for misoprostol. No further cases have been found since most clinicians and large clinical
organizations modified their practice to include one or more of the following interventions: use of prophylactic
antibiotics, use of a non-vaginal route of administration, or counseling about seeking medical attention in case of
signs of life-threatening infection. However, it is uncertain whether these interventions, and which intervention,
has prevented further cases of clostridial sepsis. (See 'Fever and infection' below.)
There are no randomized trials regarding use of prophylactic antibiotics for first-trimester medication abortion.
The largest study was an observational study conducted by Planned Parenthood of over 227,000 women with
gestational ages up to 63 days who underwent mifepristone/misoprostol abortion [33]; the rate of serious
infection decreased from 0.93 to 0.06 per 1000 women with use of prophylactic doxycycline (100 mg orally twice
a day for 7 days, starting on the day of mifepristone administration) compared with no antimicrobial prophylaxis.
Doxycycline provides coverage for chlamydia, most gonorrhea strains, and has in vitro efficacy against clostridial
species. Based on these data, the number needed to treat with a week of doxycycline is more than 5000 women
to prevent one serious infection requiring intravenous antibiotics. Of note, during the time period of the study, the
route of administration of misoprostol was also changed from vaginal to buccal; therefore, it is possible that this
is also partially responsible for the decrease in infection rate.
The disadvantages of routine use of prophylactic antibiotics include: cost, increased complexity of the regimen,
and antibiotic resistance.
The Society of Family Planning (SFP) states that, although individual practitioners may decide to use antibiotics
with provision of medication abortion, the SFP does not believe universal antibiotics is required for all women
having a medication abortion [54]. They also make the following recommendation based on limited or
inconsistent scientific evidence: although the risk of serious infection is low, recent data indicate that there may
be significant reduction in the risk of serious infection by providing treatment doses of doxycycline starting at the
time the medication abortion treatment is initiated.
Given the available evidence, we suggest universal use of antibiotic prophylaxis for first-trimester medication
abortion. This is a reasonable choice for those who value potential prevention of rare cases of severe infection
more than the disadvantages associated with routine antibiotic use.
Since decisions regarding use of prophylactic antibiotics are made based upon weak evidence, we advise that
the women undergoing first-trimester medication abortion be counseled about this controversy and be involved in
making this decision on an individual basis.
Further instructions — The patient should be given further instructions regarding returning to clinic for a
misoprostol dose or self-administration.
Written and verbal instructions should be given regarding symptoms and adverse effects and what to do in the
case of significant pain, bleeding, or other adverse reactions. For pain, a nonsteroidal anti-inflammatory drug
(NSAID) may be taken. If pain is unrelieved, the patient should call her clinician and an oral narcotic analgesia
may be prescribed. Analgesic, antiemetic, and antidiarrheal medicines can be taken, as required. She should
also be given a telephone number to call with questions or in case of an emergency.
Misoprostol — Misoprostol administration varies by timing, setting, route of administration and dose. This is
discussed in detail above. (See 'Misoprostol' above.)
Follow-up — Most clinicians have the patient return to clinic for a final visit within two weeks after treatment to
ensure that the pregnancy was completely expelled, to identify any complications requiring treatment, and to
provide contraception.
Women prefer fewer clinic visits for abortion care. To reduce the need for an additional visit, studies have
evaluated the feasibility, safety, and efficacy of self-assessment rather than a clinic visit for confirmation of
abortion completion. Self-assessment appears to result in similar rates of detection of incomplete expulsion (the
abortion is incomplete) and complications, but not ongoing pregnancy (the pregnancy continues to develop).
Thus, self-assessment is not commonly used due to concerns about rare cases of undetected ongoing
pregnancy (approximately 1 percent), which may not be detected until the second trimester. Incomplete
expulsion and complications (eg, infection) are usually symptomatic, prompting evaluation for prolonged or heavy
bleeding or fever, but ongoing pregnancy may not have concerning symptoms that alert the patient, and
therefore may go undetected into the second trimester.
Research evaluating self-assessment for medication abortion outcome have found that the risk of an
undiagnosed ongoing pregnancy increases with increasing gestational age at the time of treatment and
decreases with an approach that combines use of a home pregnancy test with standardization of both the
questions and criteria used for counseling and telephone follow-up [55-58]. For protocols that use this type of
approach, a systematic review of follow-up protocols included eight comparative studies and found that the
sensitivity for detecting an ongoing pregnancy was ≥90 percent [58]. It is important to note that all but one of the
studies in the systematic review utilized a low sensitivity urine pregnancy test (a positive result requires a urine
human chorionic gonadotropin [hCG] >1000 mIU/mL); these tests are commercially available in Europe, but not
in the United States.
A randomized trial of women who underwent medication abortion at <63 days of gestation (n = 924) compared
self-assessment (a low sensitivity urine hCG test to be performed within three weeks posttreatment and a phone
call at one month) with a routine postabortion clinic visit (urine or serum hCG testing and/or ultrasound) [59].
Interestingly, among women who declined to participate in the trial, a common reason was the desire to avoid
follow-up visits, and trial participants reported that they prefer self-assessment to a routine clinic visit. Similar to
previous studies, the self-assessment group and routine follow-up groups had similar rates of complete abortion
(94 and 95 percent), but the self-assessment group had three cases of ongoing pregnancy that were not
detected by the urine hCG test and all were discovered in the second trimester, compared with no ongoing
pregnancies in the routine follow-up group. Thus, to reliably detect ongoing pregnancy, we recommend a follow-
up clinic visit with clinical evaluation. If self-assessment is strongly desired or a clinic visit is not possible,
clinicians should counsel on both the risk and the symptoms of ongoing pregnancy, and follow a protocol that
includes use of urine pregnancy testing and a standardized telephone encounter.
Confirming complete abortion — Confirming complete expulsion of the pregnancy involves taking a history
and performing a pelvic examination; ultrasound examination is also performed by most clinicians. Women who
do not expel the pregnancy after medication abortion require surgical evacuation. (See "Surgical termination of
pregnancy: First trimester".)
In most studies of medication termination of pregnancy, the number of women lost-to-follow-up ranges from 0.6
to 5 percent [60], although it reached 11 percent in one study [61]. The need for medical confirmation of
pregnancy termination must be emphasized to users of this method, and women must be informed of the
possibility of congenital abnormalities in the event that pregnancy continues. (See 'Teratogenicity' below.)
A history of vaginal bleeding and cramping is not sufficient evidence that the pregnancy has been terminated. A
lack of bleeding, however, can be a sign of ongoing pregnancy. The patient should be asked whether she passed
what appeared to be tissue and whether this passage of tissue coincided with several hours of severe cramps
that decreased in severity after the tissue was passed.
A pelvic examination finding of a uterus that is firm and of nongravid size may be used for confirmation of
complete abortion without the use of ultrasound [62]. Confirmation of expulsion with pelvic ultrasound is required
if incomplete abortion is suspected [63,64]. Signs and symptoms of an incomplete abortion include: ongoing
cramping or bleeding, dilated cervix, uterus enlarged or unchanged from the initial examination.
On pelvic ultrasound, absence of a gestational sac is confirmation of a complete abortion. Heterogeneous

echoes in the uterus without a gestational sac are not evidence of incomplete expulsion [64]. Measured
endometrial thickness on transvaginal ultrasound is not a clinically useful predictor for the subsequent need for
surgical intervention [65-69].
Serum hCG testing is not typically used to confirm complete abortion. A single measurement of hCG at the
follow-up visit is not informative, because hCG concentration may remain elevated for weeks after complete
abortion.
Evaluating for complications — The history and clinical examination are also useful to evaluate for side
effects and complications. The patient should be asked about continued pain, fever, or excessive vaginal
bleeding. (See 'Side effects and complications' below.)
Postabortion contraception — Contraception should be addressed at the follow-up visit, if not sooner. The
patient should be counseled that ovulation usually occurs by three weeks after medication abortion and another
pregnancy can occur before resumption of normal menses [70]. Post-termination contraception is discussed in
detail separately. (See "Postabortion contraception".)
SIDE EFFECTS AND COMPLICATIONS — The side effects and complications with medication abortion
generally include those associated with the regimen as a whole (mifepristone and misoprostol) [24]. Side effects
primarily consist of gastrointestinal discomfort (nausea, vomiting, diarrhea), pain, and excessive vaginal
bleeding. Some women experience headache, dizziness, or fatigue. On occasion, surgical intervention may be
required to terminate the pregnancy if side effects are poorly tolerated (eg, severe pain or vomiting) [49].
Complications include hemorrhage, infection, incomplete abortion, and unrecognized ectopic pregnancy. Rare
cases of fatal sepsis have occurred. In a study of over 200,000 medication abortion procedures, a significant
adverse event occurred in 0.16 percent of cases, with emergency department treatment in 0.10 percent and
hospital admission in 0.06 percent [6].
Abdominal pain — Abdominal pain and cramps are experienced by nearly all women undergoing medication
abortion. The pain is usually self-limited and typically is most severe shortly after misoprostol is taken until the
expulsion of the pregnancy. Many women require one or more medications for pain relief. Typically, nonsteroidal
anti-inflammatory drugs (NSAIDs) are sufficient [71], but pain is relieved in some women only with opioids. Pain
symptoms that are concerning for pelvic infection or other complications (eg, ectopic pregnancy) include: pain
that increases in severity and frequency after the bleeding has begun to subside or a persistent pain sensation
that is sharp or unilateral or otherwise not typical of menstrual-like cramps. Patients presenting with severe or
atypical pain should be evaluated for infection, ectopic pregnancy and other possible causes. (See "Evaluation of
the adult with abdominal pain".)
In theory, NSAIDs, including aspirin, may potentially decrease the efficacy of medication abortion due to the
antiprostaglandin properties of these drugs. However, in a study of medication abortion regarding this issue,
NSAIDs did not interfere with the action of methotrexate and misoprostol to induce uterine contractions and
pregnancy expulsion [72]. In another study in women with gestations of 13 to 22 weeks, co-treatment with an
NSAID and misoprostol did not interfere with the action of mifepristone and/or misoprostol to induce uterine
contractions and pregnancy expulsion [73].
Heavy or prolonged bleeding — Vaginal bleeding is common and typically heavier than a period, but not
usually excessive (figure 1). In one study, the mean fall in hemoglobin was 0.7 g/dL and fewer than 8 percent of
patients had a loss exceeding 2 g/dL [74]. When objectively measured, blood loss ranged from 84 to 101 mL
compared to a mean loss of 53 mL in women undergoing surgical abortion [75]. Blood loss was greater in
pregnancies of longer duration [76].
The mean duration of bleeding in women undergoing medication termination of pregnancy ranges from 8 to 17
days [60], but may be more prolonged. In one study, as an example, 9 percent of women still reported mild
bleeding after 30 days and 1 percent after 60 days [49]. The perception among women is that the bleeding is
more pronounced after medication abortion than after surgical abortion because of the duration, rather than the
volume, of blood loss. Attempts to reduce the duration of bleeding by administration of an oral contraceptive or
methotrexate have been ineffective [77,78].
Blood loss usually is not severe enough to require therapy. In a large study, blood transfusion was required in
only 0.05 percent of procedures [6]. For patients with excessive or prolonged bleeding, incomplete abortion
should be excluded. Retained products of conception should be suspected if bleeding persists for more than one
week or if bleeding increases rather than decreases with time.
If retained products of conception are present, uterine aspiration should be performed. Patients should be
evaluated for infection, since postabortal endometritis may result in continued bleeding. For other women, severe
bleeding may be controlled with uterotonics or uterine packing. Fluid resuscitation or transfusion should be given
as needed. It is rare for hemorrhage to be so severe or life-threatening that hysterectomy or uterine artery
embolization would be indicated after first-trimester medication abortion.
Gastrointestinal discomfort — Nausea, vomiting, and diarrhea are frequently reported adverse events and are
associated with the prostaglandin component of the regimen. These symptoms are typically self-limited. Nausea
occurs in 34 to 72 percent of women, vomiting in 12 to 41 percent, and diarrhea in 3 to 22 percent [60]. Women
describe approximately 20 percent of these gastrointestinal side effects as severe [49]. The incidence of
gastrointestinal discomfort is higher with oral rather than vaginal or buccal administration of misoprostol and with
increase in duration of gestation [49]. Antiemetics are rarely required. (See 'Route of administration and dose'
above.)
Incomplete abortion or ongoing pregnancy — Incomplete abortion refers to the incomplete expulsion of the
products of conception. An ongoing pregnancy is an incomplete abortion in which the pregnancy continues to
develop (ie, has a rising serum human chorionic gonadotropin [hCG]). This raises concern for teratogenic effects
on a potential fetus or an expanding ectopic pregnancy.
First-trimester mifepristone/misoprostol abortion results in an incomplete abortion in 2 to 8 percent of procedures

[28-30,42,49,79-82]. Outcomes are reviewed below. (See 'Outcome' below.)
If the pregnancy has not been expelled, patients can be treated with an additional dose of misoprostol or surgical
evacuation, at any time from 4 hours to 12 days after administration of the misoprostol. Most women who receive
a second dose of misoprostol for incomplete expulsion do expel the gestation, but the rate of expulsion after a
second dose is much lower than after the first dose. Therefore, if urgent surgical intervention is not clinically
warranted, women should be given the option of a second dose of misoprostol or surgical intervention after
appropriate counseling. As an example, in a large case series, more than half of women expelled a retained
gestational sac after receiving an additional vaginal dose of misoprostol; the few patients with persistent cardiac
activity had a lower expulsion rate (5 of 14) [83].
Teratogenicity — Rarely, women choose to continue a pregnancy after a failed medication abortion or a
continuing pregnancy is not recognized. Because of a potential teratogenic risk, surgical abortion should be
performed in cases of failed pregnancy termination [1].
A review of 71 cases of continuing pregnancy reported malformations in 8 cases [84]. Prostaglandins, notably
misoprostol, have been associated with development of congenital abnormalities in retrospective studies [85].
The malformations have included scalp or skull defects, cranial nerve palsies (Mobius syndrome), and limb
deficiencies (eg, equinovarus) [86-89]. The rise in uterine pressure related to uterine contractions or vascular
spasm may be the mechanism contributing to these teratogenic effects [86-89].
Ectopic pregnancy — Rarely, ectopic pregnancy is diagnosed after receiving mifepristone/misoprostol for
medication abortion. This occurs in approximately 7 to 20 per 100,000 procedures [6,90]. In one large study,
there were 8 ectopic pregnancies, 1 of which resulted in death, among over 200,000 medication abortions [6].
Ectopic pregnancy should be excluded during the initial evaluation of the patient. As noted, ectopic pregnancy is
a life-threatening condition and women with abdominal pain or vaginal bleeding that are inconsistent with typical
patterns seen during medication abortion or with no intrauterine gestation and symptoms of ongoing pregnancy
should be evaluated for an ectopic pregnancy. (See 'Pregnancy confirmation and gestational age' above and
"Ectopic pregnancy: Clinical manifestations and diagnosis".)
Fever and infection — Infection is an uncommon complication of medication abortion. However, there have
been serious and fatal infections following medication abortion that, although rare, require clinician vigilance in
early identification and treatment. In addition, fever without infection may be associated with misoprostol.
Fever, even in the absence of infection, is a common effect of misoprostol, reported in 5 to 88 percent of patients
undergoing first-trimester abortion [91-93]. Women with fever should be evaluated for localizing signs of
infection, primarily endometritis.
Medication abortion does not involve instrumentation of the uterus and thus has a lower incidence of infection
than surgical abortion. In surgical abortion, postabortal endometritis is thought to arise from the introduction of
vaginal and skin flora into the endometrial cavity. The incidence of endometritis following medication abortion is
lower than after surgical abortion [49]. In a large retrospective study of women who underwent first-trimester
medication abortion, the incidence of infection was 0.016 percent and the rate of treatment with intravenous
antibiotics was 0.02 percent [6].
Fever may be a late sign of postabortal endometritis, or some women may not develop fever. Women with the
following symptoms or signs should be evaluated for infection: fever, chills, body aches, excessive or prolonged
vaginal bleeding, moderate to severe pelvic pain that persists for a day or more after expulsion of the pregnancy,
or a purulent vaginal discharge [94-97]. Postabortal endometritis is treated in the same manner as other types of
postpartum endometritis. (See "Postpartum endometritis".)
Clostridial sepsis — Clostridial sepsis has been responsible for seven deaths following first-trimester
medication abortion in the United States and Canada between 2000 and 2010 [94-97]. In the majority of cases,
the microbial agent identified was Clostridium sordellii. C. perfringens was identified in one case, and in an
additional case, a patient with a fatal C. perfringens infection received laminaria and vaginal misoprostol, but no
mifepristone to terminate a 19-week gestation. With one exception, all of the septic deaths involved the off-label
dosing regimen consisting of 200 mg of oral mifepristone followed by 800 mcg of vaginal misoprostol.
Reports are rare of fulminant lethal clostridial sepsis in women of childbearing age, but there is generally an
association with childbirth, spontaneous and induced abortion, or cervical or uterine procedures [98,99]. Sepsis
related to C. sordellii is difficult to diagnose because of its subtle clinical manifestations and may rapidly progress
to death (death within three days of hospitalization) [100].
A causal relationship between sepsis and the use of mifepristone has not been established. The US Food and
Drug Administration (FDA) is working with the manufacturers of mifepristone and misoprostol tablets to conduct
special tests to ensure there is no contamination of either product with C. sordellii. Because of the adverse
events described above, the FDA required that a black box warning be included as part of mifepristone drug
information.
Physiologic explanations for the development of serious infection have been proposed. Both misoprostol and
mifepristone induce cervical dilation. Studies in rats show that cervical dilation with mifepristone may allow for
ascending infection of necrotic decidual tissue [101].
Endocrinologic and immune mechanisms may also interact to increase the risk of infection in women undergoing
mifepristone/misoprostol abortion. Mifepristone-induced glucocorticoid receptor blockade may result in an
inappropriate cytokine response of the immune system [100]. Toxins from C. sordellii may also repress
glucocorticoid activity. Mifepristone and toxins additively prevent glucocorticoid suppression of tumor necrosis
factor alpha, therefore interfering with the immune response [102]. Misoprostol may suppress the immune
reaction to clostridial infections [103,104].
Mifepristone/prostaglandin abortion had been used widely in Europe before its introduction in the United States.
However, there have not been similar cases of clostridial sepsis. Two deaths have been reported, neither related
to infection. One hypothesis for absence of similar cases of C. sordellii infection in Europe is that vaginal dosing
was uncommon in Europe [34] and prophylactic antibiotic treatment often given [31,34].
In response to the fatal infections reported, and without an identified etiology, some clinicians, including Planned
Parenthood (the largest abortion provider in the United States) have started giving all patients prophylactic
antibiotics. (See 'Prophylactic antibiotics' above.)
Clinicians should be aware of the presenting symptoms of clostridial sepsis. Patients with C. sordellii sepsis
following abortion generally presented without fever, bacteremia, rash, or significant findings on pelvic
examination, but did have dramatic leukocytosis with a marked left shift, hemoconcentration, tachycardia,
hypotension crampy abdominal pain, pleural/peritoneal effusion, and general malaise (weakness, nausea,
vomiting, diarrhea). Gas gangrene was not noted. There should be a high index of suspicion of sepsis if these
findings are present, and the patient should be evaluated and treated immediately. Optimal therapy is unproven,
but probably includes surgical debridement, removal of infected organs (eg, hysterectomy), and antibiotics with
good anaerobic activity [98]. Diagnosis may be challenging, since the organism can be difficult to identify
because of fastidious anaerobic growth, variable staining characteristics, and complex biochemical profiles. C.
sordellii appears to a rare transient organism in the vagina [105]. (See "Toxic shock syndrome due to Clostridium
sordellii", section on 'Treatment'.)
Mortality — There have been few cases of death (approximately 10 cases) associated with first-trimester
medication abortion. In North America, the deaths have been due mainly to clostridial sepsis and ectopic
pregnancy. (See 'Fever and infection' above and 'Ectopic pregnancy' above.)
Despite these reports of adverse events, the total experience in the industrialized world indicates that the fatality
rate for medication abortion does not appear to be significantly higher than that of surgical abortion (case fatality
rate 0.6/100,000 legal induced abortions) [106,107] and is much lower than that of pregnancy (12 maternal
deaths/100,000 live births). (See "Overview of maternal mortality and morbidity", section on 'Maternal mortality
ratio'.)
OUTCOME — First-trimester mifepristone/misoprostol abortion is successful in 92 to 98 percent of procedures

[28-30,42,49,79-82].
The efficacy varies with several factors:
● Gestational duration
● Route of administration and dose of misoprostol
● Parity – The rate of successful abortion is lower with increasing parity and in women who have had a
previous abortion [49]. It is theorized that pregnancy is more successfully established at an earlier
gestational stage in parous women than in nulliparous women [43,108,109].
Up to 49 days of gestation — The successful completion of medication abortion in pregnancies up to 49 days

of gestation ranges from 91 to 98 percent [28,42,49,79]. In one early large multicenter United States trial, the
lower success rate of 92 percent may be related to the lack of experience with medication abortion, as well as
stringent criteria for success (figure 2) [49].
Complete expulsion before prostaglandin administration occurred in 1 to 5 percent of women in the United States
trial; the frequency was higher at earlier gestations (figure 2) [49]. Similar results were noted in the French trials
[28]. Another 44 to 78 percent of women aborted in the four-hour observation period after oral misoprostol (figure
3) [49]. The percentage was higher after vaginal, as opposed to oral, misoprostol [29]. (See 'Route of
administration and dose' above.)
After 49 days of gestation — Mifepristone was not initially approved by the US Food and Drug Administration
(FDA) in the United States for pregnancies over 49 days because initial research reported a lower success rate
beyond this gestational age [49,80,110]; oral misoprostol was used with mifepristone in these studies (figure 2).
By comparison, success remained high (94 to 97 percent) until 63 days of gestation when buccal or vaginal
misoprostol (800 mcg) was given after mifepristone (200 mg) [29,37,60,81,82,111]. Given the comparable
success rate and excellent safety profile, the evidence-based alternative regimen supported medication abortion
through 63 days of gestation.
Medication abortion has also been investigated at later gestational ages [112-116]:
● 64 to 70 days – A randomized trial (n = 629) found similar efficacy using mifepristone 200 mg/misoprostol
buccal 800 mcg in gestations of 64 to 70 days compared with 57 to 63 days (success rate for both was 93
percent) [116]. Thus the FDA revised the labeling to include administration for pregnancies through 70 days
of gestation.
● 70 to 83 days – A prospective study (n = 253) using mifepristone 200 mg/misoprostol vaginal 800 mcg
reported successful termination of pregnancy in 97 percent of pregnancies at gestational ages 70 to 76 days
and 90 percent of those at 77 to 83 days [112]. In addition to the lower efficacy and use of vaginal
misoprostol, this regimen was administered in hospital.
● 64 to 91 days – In a retrospective study (n = 483) using mifepristone 200 mg followed by up to five doses of
misoprostol (vaginal 800 mcg initially and then 400 mcg either vaginal or oral every three hours) at 64 to 91
days of gestation reported successful termination in 95 percent of pregnancies [113]. Efficacy declined with
advancing gestational age. Surgical evacuation was required in 1 woman (1/106) at 9 to 10 weeks, but 9
(9/114) of those at 12 to 13 weeks. There were no major complications.
Use of medication abortion at gestational ages greater than 70 days has a lower efficacy and requires in-hospital
administration. Given the limited data to support this regimen, women choosing this beyond 70 days should be
counseled regarding the lower efficacy, the increased likelihood of seeing the pregnancy tissue, and the
recommendation for inpatient care.
Implications for future pregnancy — There is no evidence that medication termination of pregnancy is
associated with any increased risk of adverse outcome in subsequent pregnancies. Two studies from China did
not find an increased risk of low birth weight in nulliparous women in the pregnancy after a medication abortion
[117,118]. A well-designed study from Denmark compared the outcome of a subsequent pregnancy in women
with a history of medication or surgical first-trimester pregnancy termination [119]. Both groups had similar rates
of miscarriage, ectopic pregnancy, preterm birth, and low birth weight in the first pregnancy after their abortion.
ALTERNATIVE MEDICATION METHODS
Methotrexate — Methotrexate (50 mg/m2) followed by vaginal misoprostol (800 mcg) three to seven days later
also successfully terminates pregnancy for 88 to 96 percent of women treated [120] at less than or equal to 49
days of gestation [106]. A significant disadvantage to the mifepristone regimen is the prolonged interval from
treatment to complete abortion associated with the methotrexate regimen [60,120-122]. In one study, 23 percent
of women who aborted did so after a mean delay of 24 days [120]. It is not recommended for pregnancies over
49 days [1].
Misoprostol alone — Misoprostol given alone, whether by the vaginal or the buccal route, is less effective than
when given in combination with mifepristone [123,124]; however, the use of misoprostol alone is a reasonable
option in settings where mifepristone is not available. (See "Misoprostol as a single agent for medical termination
of pregnancy".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Abortion (The Basics)")
● Beyond the Basics topics (see "Patient education: Abortion (pregnancy termination) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Medication abortion is the termination of pregnancy with use of medications alone rather than surgery.
Mifepristone, a progesterone antagonist, is approved for use in the United States, in combination with
misoprostol, for the termination of pregnancies up to 70 days of gestation. (See 'Introduction' above.)
● The choice between medication abortion and surgical abortion in the first trimester is based upon availability,
gestational age (medication abortion is less successful in the late first trimester), and patient preference.
Given the available data, we suggest medication abortion for women who place a high value on avoiding
surgery or anesthesia and who are willing to accept more discomfort and awareness of the procedure
(Grade 2C). For other women, particularly those who place a high value on completing the procedure in one
visit, we recommend surgical abortion (Grade 1B). (See 'Medication versus surgical termination' above.)
● Contraindications for first-trimester medication abortion include: ectopic pregnancy, intrauterine device in
place, chronic adrenal failure, long-term corticosteroid therapy, bleeding diathesis, inherited porphyrias, and
lack of the ability to comply with the regimen or access to emergent care in the case of a complication (table
1). (See 'Contraindications' above.)
● The regimen approved by the US Food and Drug Administration (FDA) and recommended by the
manufacturer consists of mifepristone (200 mg orally) followed 24 to 48 hours later by misoprostol (800 mcg
buccally). An alternative evidence-based regimen extends the window for misoprostol administration to 72
hours. (See 'Medication regimen' above.)
● For women undergoing first-trimester mifepristone/misoprostol medication abortion:
• We recommend an oral mifepristone dose of 200 mg (Grade 1A). (See 'Mifepristone' above.)
• We recommend buccal administration of misoprostol rather than other routes (Grade 1B). Oral
administration of misoprostol is a reasonable option for women at ≤49 days of gestation. We do not
prefer vaginal administration of misoprostol due to an association with a rare but life-threatening
infection. (See 'Route of administration and dose' above and 'Clostridial sepsis' above.)
• Mifepristone followed in 24 to 72 hours by misoprostol as well as self-administration of misoprostol has

been found to be effective. (See 'Timing' above and 'Clinician versus self-administration' above.)
● First-trimester medication is successful in 92 to 98 percent of procedures. Failed medication abortion is

treated with surgical uterine evacuation. (See 'Outcome' above.)
● We suggest universal use of antibiotic prophylaxis for first-trimester medication abortion (Grade 2C). This is
a reasonable choice for those who value potential prevention of rare cases of severe infection more than the
disadvantages associated with routine antibiotic use. (See 'Prophylactic antibiotics' above.)
● Side effects following administration of mifepristone and misoprostol primarily consist of abdominal pain,
excessive bleeding, and gastrointestinal discomfort. Complications include hemorrhage, infection,
incomplete abortion, and unrecognized ectopic pregnancy. Rare cases of fatal sepsis have occurred. (See
'Side effects and complications' above.)
● Following first-trimester medication abortion, we recommend a follow-up clinic visit with clinical evaluation
rather than self-assessment with no clinic visit (Grade 1B). If self-assessment is strongly desired or a clinic
visit is not possible, clinicians should counsel on both the risk and the symptoms of ongoing pregnancy, and
follow a protocol that includes use of urine pregnancy testing and a standardized telephone encounter. (See
'Follow-up' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. ACOG. ACOG practice bulletin. Clinical management guidelines of obstetrician-gynecologists. Number 67,
October 2005. Medical management of abortion. Obstet Gynecol 2005; 106:871.
2. Pazol K, Creanga AA, Zane SB, et al. Abortion surveillance--United States, 2009. MMWR Surveill Summ
2012; 61:1.
3. Ngo TD, Park MH, Free C. Safety and effectiveness of termination services performed by doctors versus
midlevel providers: a systematic review and analysis. Int J Womens Health 2013; 5:9.
4. Henshaw RC, Naji SA, Russell IT, Templeton AA. A comparison of medical abortion (using mifepristone and
gemeprost) with surgical vacuum aspiration: efficacy and early medical sequelae. Hum Reprod 1994;
9:2167.
5. Jensen JT, Astley SJ, Morgan E, Nichols MD. Outcomes of suction curettage and mifepristone abortion in
the United States. A prospective comparison study. Contraception 1999; 59:153.
6. Cleland K, Creinin MD, Nucatola D, et al. Significant adverse events and outcomes after medical abortion.
Obstet Gynecol 2013; 121:166.
7. Robson SC, Kelly T, Howel D, et al. Randomised preference trial of medical versus surgical termination of
pregnancy less than 14 weeks' gestation (TOPS). Health Technol Assess 2009; 13:1.
8. Rørbye C, Nørgaard M, Nilas L. Medical versus surgical abortion: comparing satisfaction and potential
confounders in a partly randomized study. Hum Reprod 2005; 20:834.
9. Jensen JT, Harvey SM, Beckman LJ. Acceptability of suction curettage and mifepristone abortion in the
United States: a prospective comparison study. Am J Obstet Gynecol 2000; 182:1292.
10. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm11132
3.htm (Accessed on March 30, 2016).
11. http://www.earlyoptionpill.com/section/health_professionals/prescribing_information (Accessed on February
15, 2013).
12. Cable EE, Pepe JA, Donohue SE, et al. Effects of mifepristone (RU-486) on heme metabolism and
cytochromes P-450 in cultured chick embryo liver cells, possible implications for acute porphyria. Eur J
Biochem 1994; 225:651.
13. Heikinheimo O. Clinical pharmacokinetics of mifepristone. Clin Pharmacokinet 1997; 33:7.
14. Sarkar NN. Mifepristone: bioavailability, pharmacokinetics and use-effectiveness. Eur J Obstet Gynecol
Reprod Biol 2002; 101:113.
15. Heikinheimo O, Kekkonen R, Lähteenmäki P. The pharmacokinetics of mifepristone in humans reveal
insights into differential mechanisms of antiprogestin action. Contraception 2003; 68:421.
16. Gupta A, Lawrence AT, Krishnan K, et al. Current concepts in the mechanisms and management of drug-
induced QT prolongation and torsade de pointes. Am Heart J 2007; 153:891.
17. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202107s000lbl.pdf (Accessed on February 05,
2014).
18. American College of Obstetricians and Gynecologists. Mifepristone for medical pregnancy termination. AC
OG Committee Opinion No 245. American College of Obstetricians and Gynecologists, Washington, DC 20
00.
19. Greene MF, Drazen JM. A New Label for Mifepristone. N Engl J Med 2016; 374:2281.
20. Wildschut H, Both MI, Medema S, et al. Medical methods for mid-trimester termination of pregnancy.
Cochrane Database Syst Rev 2011; :CD005216.
21. Creinin MD, Pymar HC, Schwartz JL. Mifepristone 100 mg in abortion regimens. Obstet Gynecol 2001;
98:434.
22. World Health Organization Task Force on Post-ovulatory Methods for Fertility Regulation, 2001.
23. Prasad RN, Choolani M. Termination of early human pregnancy with either 50 mg or 200 mg single oral
dose of mifepristone (RU486) in combination with either 0.5 mg or 1.0 mg vaginal gemeprost. Aust N Z J
Obstet Gynaecol 1996; 36:20.
24. Spitz IM, Bardin CW. Mifepristone (RU 486)--a modulator of progestin and glucocorticoid action. N Engl J
Med 1993; 329:404.
25. Couzinet B, Le Strat N, Ulmann A, et al. Termination of early pregnancy by the progesterone antagonist RU
486 (Mifepristone). N Engl J Med 1986; 315:1565.
26. Spitz IM, Bardin CW. Clinical pharmacology of RU 486--an antiprogestin and antiglucocorticoid.
Contraception 1993; 48:403.
27. Bartley J, Brown A, Elton R, Baird DT. Double-blind randomized trial of mifepristone in combination with
vaginal gemeprost or misoprostol for induction of abortion up to 63 days gestation. Hum Reprod 2001;
16:2098.
28. Silvestre L, Dubois C, Renault M, et al. Voluntary interruption of pregnancy with mifepristone (RU 486) and
a prostaglandin analogue. A large-scale French experience. N Engl J Med 1990; 322:645.
29. el-Refaey H, Rajasekar D, Abdalla M, et al. Induction of abortion with mifepristone (RU 486) and oral or
vaginal misoprostol. N Engl J Med 1995; 332:983.
30. Schaff EA, Fielding SL, Eisinger SH, et al. Low-dose mifepristone followed by vaginal misoprostol at 48
hours for abortion up to 63 days. Contraception 2000; 61:41.
31. Fiala C, Gemzel-Danielsson K. Review of medical abortion using mifepristone in combination with a
prostaglandin analogue. Contraception 2006; 74:66.
32. Tang OS, Ho PC. The pharmacokinetics and different regimens of misoprostol in early first-trimester
medical abortion. Contraception 2006; 74:26.
33. Fjerstad M, Trussell J, Sivin I, et al. Rates of serious infection after changes in regimens for medical
abortion. N Engl J Med 2009; 361:145.
34. Darney PD. Deaths associated with medication abortion. Contraception 2005; 72:319.
35. Aubeny E, Chatellier G. A randomized comparison of mifepristone and self-administered oral or vaginal
misoprostol for early abortion. Eur J Contracept Reprod Health Care 2000; 5:171.
36. Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol at one day after
mifepristone for early medical abortion. Contraception 2001; 64:81.
37. Winikoff B, Dzuba IG, Creinin MD, et al. Two distinct oral routes of misoprostol in mifepristone medical
abortion: a randomized controlled trial. Obstet Gynecol 2008; 112:1303.
38. Kulier R, Gülmezoglu AM, Hofmeyr GJ, et al. Medical methods for first trimester abortion. Cochrane
Database Syst Rev 2004; :CD002855.
39. Middleton T, Schaff E, Fielding SL, et al. Randomized trial of mifepristone and buccal or vaginal misoprostol
for abortion through 56 days of last menstrual period. Contraception 2005; 72:328.
40. Chong E, Tsereteli T, Nguyen NN, Winikoff B. A randomized controlled trial of different buccal misoprostol
doses in mifepristone medical abortion. Contraception 2012; 86:251.
41. Raghavan S, Comendant R, Digol I, et al. Comparison of 400 mcg buccal and 400 mcg sublingual
misoprostol after mifepristone medical abortion through 63 days' LMP: a randomized controlled trial.
42. Peyron R, Aubény E, Targosz V, et al. Early termination of pregnancy with mifepristone (RU 486) and the
orally active prostaglandin misoprostol. N Engl J Med 1993; 328:1509.
43. Ashok PW, Templeton A, Wagaarachchi PT, Flett GM. Factors affecting the outcome of early medical
abortion: a review of 4132 consecutive cases. BJOG 2002; 109:1281.
44. Coyaji K, Krishna U, Ambardekar S, et al. Are two doses of misoprostol after mifepristone for early abortion
better than one? BJOG 2007; 114:271.
45. Fjerstad M, Sivin I, Lichtenberg ES, et al. Effectiveness of medical abortion with mifepristone and buccal
misoprostol through 59 gestational days. Contraception 2009; 80:282.
46. Schaff EA, Fielding SL, Westhoff C, et al. Vaginal misoprostol administered 1, 2, or 3 days after
mifepristone for early medical abortion: A randomized trial. JAMA 2000; 284:1948.
47. Wedisinghe L, Elsandabesee D. Flexible mifepristone and misoprostol administration interval for first-
trimester medical termination. Contraception 2010; 81:269.
48. Ngo TD, Park MH, Shakur H, Free C. Comparative effectiveness, safety and acceptability of medical
abortion at home and in a clinic: a systematic review. Bull World Health Organ 2011; 89:360.
49. Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol
in the United States. N Engl J Med 1998; 338:1241.
50. Kapp N, Whyte P, Tang J, et al. A review of evidence for safe abortion care. Contraception 2013; 88:350.
51. Creinin MD, Schreiber CA, Bednarek P, et al. Mifepristone and misoprostol administered simultaneously
versus 24 hours apart for abortion: a randomized controlled trial. Obstet Gynecol 2007; 109:885.
52. Creinin MD, Fox MC, Teal S, et al. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours
after mifepristone for abortion. Obstet Gynecol 2004; 103:851.
53. Ulmann A, Silvestre L, Chemama L, et al. Medical termination of early pregnancy with mifepristone (RU
486) followed by a prostaglandin analogue. Study in 16,369 women. Acta Obstet Gynecol Scand 1992;
71:278.
54. Achilles SL, Reeves MF, Society of Family Planning. Prevention of infection after induced abortion: release
date October 2010: SFP guideline 20102. Contraception 2011; 83:295.
55. Jackson AV, Dayananda I, Fortin JM, et al. Can women accurately assess the outcome of medical abortion
based on symptoms alone? Contraception 2012; 85:192.
56. Perriera LK, Reeves MF, Chen BA, et al. Feasibility of telephone follow-up after medical abortion.
57. Cameron ST, Glasier A, Dewart H, et al. Telephone follow-up and self-performed urine pregnancy testing
after early medical abortion: a service evaluation. Contraception 2012; 86:67.
58. Grossman D, Grindlay K. Alternatives to ultrasound for follow-up after medication abortion: a systematic
review. Contraception 2011; 83:504.
59. Oppegaard KS, Qvigstad E, Fiala C, et al. Clinical follow-up compared with self-assessment of outcome
after medical abortion: a multicentre, non-inferiority, randomised, controlled trial. Lancet 2015; 385:698.
60. Christin-Maitre S, Bouchard P, Spitz IM. Medical termination of pregnancy. N Engl J Med 2000; 342:946.
61. Broome, M. Using mifepristone in a family planning clinic. Br J Fam Plan 1994; 20:11.
62. Clark W, Bracken H, Tanenhaus J, et al. Alternatives to a routine follow-up visit for early medical abortion.
Obstet Gynecol 2010; 115:264.
63. Cowett AA, Cohen LS, Lichtenberg ES, Stika CS. Ultrasound evaluation of the endometrium after medical
termination of pregnancy. Obstet Gynecol 2004; 103:871.
64. Bar-Hava I, Aschkenazi S, Orvieto R, et al. Spectrum of normal intrauterine cavity sonographic findings
after first-trimester abortion. J Ultrasound Med 2001; 20:1277.
65. Harwood B, Meckstroth KR, Mishell DR, Jain JK. Serum beta-human chorionic gonadotropin levels and
endometrial thickness after medical abortion. Contraception 2001; 63:255.
66. Luise C, Jermy K, Collons WP, Bourne TH. Expectant management of incomplete, spontaneous first-
trimester miscarriage: outcome according to initial ultrasound criteria and value of follow-up visits.
Ultrasound Obstet Gynecol 2002; 19:580.
67. Creinin MD, Harwood B, Guido RS, et al. Endometrial thickness after misoprostol use for early pregnancy
failure. Int J Gynaecol Obstet 2004; 86:22.
68. Reynolds A, Ayres-de-Campos D, Costa MA, Montenegro N. How should success be defined when
attempting medical resolution of first-trimester missed abortion? Eur J Obstet Gynecol Reprod Biol 2005;
118:71.
69. Reeves MF, Fox MC, Lohr PA, Creinin MD. Endometrial thickness following medical abortion is not
predictive of subsequent surgical intervention. Ultrasound Obstet Gynecol 2009; 34:104.
70. Schreiber CA, Sober S, Ratcliffe S, Creinin MD. Ovulation resumption after medical abortion with
mifepristone and misoprostol. Contraception 2011; 84:230.
71. Livshits A, Machtinger R, David LB, et al. Ibuprofen and paracetamol for pain relief during medical abortion:
a double-blind randomized controlled study. Fertil Steril 2009; 91:1877.
72. Creinin MD, Shulman T. Effect of nonsteroidal anti-inflammatory drugs on the action of misoprostol in a
regimen for early abortion. Contraception 1997; 56:165.
73. Fiala C, Swahn ML, Stephansson O, Gemzell-Danielsson K. The effect of non-steroidal anti-inflammatory
drugs on medical abortion with mifepristone and misoprostol at 13-22 weeks gestation. Hum Reprod 2005;
20:3072.
74. Thonneau P, Poirel H, Fougeyrollas B, et al. A comparative analysis of fall in haemoglobin following
abortions conducted by mifepristone (600 mg) and vacuum aspiration. Hum Reprod 1995; 10:1512.
75. Chan YF, Ho PC, Ma HK. Blood loss in termination of early pregnancy by vacuum aspiration and by
combination of mifepristone and gemeprost. Contraception 1993; 47:85.
76. Rodger MW, Baird DT. Blood loss following induction of early abortion using mifepristone (RU 486) and a
prostaglandin analogue (gemeprost). Contraception 1989; 40:439.
77. Martin CW, Brown AH, Baird DT. A pilot study of the effect of methotrexate or combined oral contraceptive
on bleeding patterns after induction of abortion with mifepristone and a prostaglandin pessary.
78. Tang OS, Gao PP, Cheng L, et al. A randomized double-blind placebo-controlled study to assess the effect
of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol. Hum
Reprod 1999; 14:722.
79. Pregnancy termination with mifepristone and gemeprost: a multicenter comparison between repeated
doses and a single dose of mifepristone. World Health Organization. Fertil Steril 1991; 56:32.
80. Aubény E, Peyron R, Turpin CL, et al. Termination of early pregnancy (up to 63 days of amenorrhea) with
mifepristone and increasing doses of misoprostol [corrected]. Int J Fertil Menopausal Stud 1995; 40 Suppl
2:85.
81. Baird DT, Sukcharoen N, Thong KJ. Randomized trial of misoprostol and cervagem in combination with a
reduced dose of mifepristone for induction of abortion. Hum Reprod 1995; 10:1521.
82. Ashok PW, Penney GC, Flett GM, Templeton A. An effective regimen for early medical abortion: a report of
2000 consecutive cases. Hum Reprod 1998; 13:2962.
83. Schwarz EB, Smith R, Steinauer J, et al. Measuring the effects of unintended pregnancy on women's
quality of life. Contraception 2008; 78:204.
84. Sitruk-Ware R, Davey A, Sakiz E. Fetal malformation and failed medical termination of pregnancy. Lancet
1998; 352:323.
85. Orioli IM, Castilla EE. Epidemiological assessment of misoprostol teratogenicity. BJOG 2000; 107:519.
86. Fonseca W, Alencar AJ, Mota FS, Coelho HL. Misoprostol and congenital malformations. Lancet 1991;
338:56.
87. Gonzalez CH, Vargas FR, Perez AB, et al. Limb deficiency with or without Möbius sequence in seven
Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am J Med Genet
1993; 47:59.
88. Gonzalez CH, Marques-Dias MJ, Kim CA, et al. Congenital abnormalities in Brazilian children associated
with misoprostol misuse in first trimester of pregnancy. Lancet 1998; 351:1624.
89. Pastuszak AL, Schüler L, Speck-Martins CE, et al. Use of misoprostol during pregnancy and Möbius'
syndrome in infants. N Engl J Med 1998; 338:1881.
90. Shannon C, Brothers LP, Philip NM, Winikoff B. Ectopic pregnancy and medical abortion. Obstet Gynecol
2004; 104:161.
91. Tang OS, Gemzell-Danielsson K, Ho PC. Misoprostol: pharmacokinetic profiles, effects on the uterus and
side-effects. Int J Gynaecol Obstet 2007; 99 Suppl 2:S160.
92. Carbonell JL, Velazco A, Varela L, et al. Misoprostol for abortion at 9-12 weeks' gestation in adolescents.
Eur J Contracept Reprod Health Care 2001; 6:39.
93. Faúndes A, Fiala C, Tang OS, Velasco A. Misoprostol for the termination of pregnancy up to 12 completed
weeks of pregnancy. Int J Gynaecol Obstet 2007; 99 Suppl 2:S172.
94. Meites E, Zane S, Gould C, C. sordellii Investigators. Fatal Clostridium sordellii infections after medical
abortions. N Engl J Med 2010; 363:1382.
95. Cohen AL, Bhatnagar J, Reagan S, et al. Toxic shock associated with Clostridium sordellii and Clostridium
perfringens after medical and spontaneous abortion. Obstet Gynecol 2007; 110:1027.
96. Sinave C, Le Templier G, Blouin D, et al. Toxic shock syndrome due to Clostridium sordellii: a dramatic
postpartum and postabortion disease. Clin Infect Dis 2002; 35:1441.
97. Wiebe E, Guilbert E, Jacot F, et al. A fatal case of Clostridium sordellii septic shock syndrome associated
with medical abortion. Obstet Gynecol 2004; 104:1142.
98. Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with Clostridium sordellii
after medical abortion. N Engl J Med 2005; 353:2352.
99. Ho CS, Bhatnagar J, Cohen AL, et al. Undiagnosed cases of fatal Clostridium-associated toxic shock in
Californian women of childbearing age. Am J Obstet Gynecol 2009; 201:459.e1.
100. Miech RP. Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii. Ann
Pharmacother 2005; 39:1483.
101. van der Schoot P. Treatment with mifepristone (RU486) and oestradiol facilitates the development of genital
septic disease after copulation in female rats. Hum Reprod 1992; 7:601.
102. Tait AS, Dalton M, Geny B, et al. The large clostridial toxins from Clostridium sordellii and C. difficile repress
glucocorticoid receptor activity. Infect Immun 2007; 75:3935.
103. Waiser J, Böhler T, Stoll J, et al. The immunosuppressive potential of misoprostol--efficacy and variability.
Clin Immunol 2003; 109:288.
104. Aronoff DM, Hao Y, Chung J, et al. Misoprostol impairs female reproductive tract innate immunity against
Clostridium sordellii. J Immunol 2008; 180:8222.
105. Chong E, Winikoff B, Charles D, et al. Vaginal and Rectal Clostridium sordellii and Clostridium perfringens
Presence Among Women in the United States. Obstet Gynecol 2016; 127:360.
106. Stubblefield PG, Carr-Ellis S, Borgatta L. Methods for induced abortion. Obstet Gynecol 2004; 104:174.
107. Elam-Evans LD, Strauss LT, Herndon J, et al. Abortion surveillance--United States, 2000. MMWR Surveill
Summ 2003; 52:1.
108. Child TJ, Thomas J, Rees M, MacKenzie IZ. A comparative study of surgical and medical procedures: 932
pregnancy terminations up to 63 days gestation. Hum Reprod 2001; 16:67.
109. Bartley J, Tong S, Everington D, Baird DT. Parity is a major determinant of success rate in medical abortion:
a retrospective analysis of 3161 consecutive cases of early medical abortion treated with reduced doses of
mifepristone and vaginal gemeprost. Contraception 2000; 62:297.
110. World Health Organisation Task Force on Post-ovulatory Methods of Fertility Regulation, Special
Programme of Research, Development and Research Training, World Health Organisation. Comparison of
two doses of mifepristone in combination with misoprostol for early medical abortion: a randomised trial.
BJOG 2000; 107:524.
111. The efficacy and tolerance of mifepristone and prostaglandin in termination of pregnancy of less than 63
days gestation; UK Multicentre Study--final results. Contraception 1997; 55:1.
112. Gouk EV, Lincoln K, Khair A, et al. Medical termination of pregnancy at 63 to 83 days gestation. Br J Obstet
Gynaecol 1999; 106:535.
113. Hamoda H, Ashok PW, Flett GM, Templeton A. Medical abortion at 64 to 91 days of gestation: a review of
483 consecutive cases. Am J Obstet Gynecol 2003; 188:1315.
114. www.plannedparenthood.org/library/ABORTION/Mif_fact.html (Accessed on March 07, 2005).
115. Bracken H, Ngoc NT, Schaff E, et al. Mifepristone followed in 24 hours to 48 hours by misoprostol for late
first-trimester abortion. Obstet Gynecol 2007; 109:895.
116. Winikoff B, Dzuba IG, Chong E, et al. Extending outpatient medical abortion services through 70 days of
gestational age. Obstet Gynecol 2012; 120:1070.
117. Yimin C, Wei Y, Weidong C, et al. Mifepristone-induced abortion and birth weight in the first subsequent
pregnancy. Int J Gynaecol Obstet 2004; 84:229.
118. Sun Y, Che Y, Gao E, et al. Induced abortion and risk of subsequent miscarriage. Int J Epidemiol 2003;
32:449.
119. Virk J, Zhang J, Olsen J. Medical abortion and the risk of subsequent adverse pregnancy outcomes. N Engl
J Med 2007; 357:648.
120. Creinin MD, Vittinghoff E, Keder L, et al. Methotrexate and misoprostol for early abortion: a multicenter trial.
I. Safety and efficacy. Contraception 1996; 53:321.
121. Wiebe E, Dunn S, Guilbert E, et al. Comparison of abortions induced by methotrexate or mifepristone
followed by misoprostol. Obstet Gynecol 2002; 99:813.
122. Borgatta L, Burnhill MS, Tyson J, et al. Early medical abortion with methotrexate and misoprostol. Obstet
Gynecol 2001; 97:11.
123. Jain JK, Dutton C, Harwood B, et al. A prospective randomized, double-blinded, placebo-controlled trial
comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of
early pregnancy. Hum Reprod 2002; 17:1477.
124. Ngoc NT, Blum J, Raghavan S, et al. Comparing two early medical abortion regimens:
mifepristone+misoprostol vs. misoprostol alone. Contraception 2011; 83:410.
Topic 3296 Version 21.0
GRAPHICS
Contraindications to medication abortion
Confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass
Intrauterine device in place
Chronic adrenal failure
Concurrent long-term corticosteroid therapy
Hemorrhagic disorders or concurrent anticoagulant therapy
Inherited porphyrias
Inability to understand the effects of the treatment procedure or to comply with its regimen
Lack of adequate access to medical facilities equipped to provide emergency treatment of incomplete abortion, blood
transfusions, and emergency resuscitation during the period from the first visit until discharged by the administering
physician
Guidelines per manufacturer (Danco laboratories).
Graphic 54726 Version 5.0
Cytochrome P450 3A4 (CYP3A4) inhibitors and inducers*
Strong inhibitors Moderate inhibitors Strong inducers Moderate inducers

Atazanavir Amiodarone ¶ Carbamazepine Bexarotene
Boceprevir Aprepitant Enzalutamide Bosentan
Ceritinib Cimetidine ¶ Fosphenytoin Dabrafenib
Clarithromycin Conivaptan Lumacaftor Dexamethasone ¶
Cobicistat and cobicistat Crizotinib Mitotane Efavirenz

containing
Cyclosporine ¶ Phenobarbital Eslicarbazepine
coformulations
Diltiazem Phenytoin Etravirine
Darunavir
Dronedarone Primidone Modafinil
Idelalisib
Erythromycin Rifabutin Nafcillin
Indinavir
Fluconazole Rifampin (rifampicin) St. John's wort
Itraconazole
Fosamprenavir Rifapentine
Ketoconazole
Fosaprepitant ¶
Lopinavir
Grapefruit juice
Mifepristone
Imatinib
Nefazodone
Isavuconazole
Nelfinavir
(isavuconazonium
Ombitasvir-paritaprevir- sulfate)
ritonavir
Netupitant
Ombitasvir-paritaprevir-
Nilotinib
ritonavir plus dasabuvir
Ribociclib
Posaconazole
Schisandra
Ritonavir and ritonavir
containing Verapamil
coformulations
Saquinavir
Telaprevir
Telithromycin
Voriconazole
Data are for systemic drug forms. Degree of inhibition or induction may be altered by dose, method, and timing of
administration. Specific drug interactions and management suggestions may be determined by using Lexi-Interact,
the drug interactions program included with UpToDate. Refer to UpToDate topics on specific agents and indications for
further details.
* The CYP3A4 inhibitors and inducers listed in this table are relevant for determining potential interactions of drugs that are
CYP3A subfamily substrates.
¶ Weak effect on CYP3A4.
Data from: Lexicomp Online (Lexi-Interact). Copyright © 1978-2017 Lexicomp, Inc. All Rights Reserved
Some reported causes and potentiators of the long QT syndrome*
Congenital Acquired (continued)

Jervell and Lange-Nielsen syndrome (including Antihistamines
"channelopathies")
Astemizole ◊, bilastine Δ, hydroxyzine, terfenadine ◊
Romano-Ward syndrome
Antineoplastic drugs
Idiopathic
Arsenic trioxide, bendamustine, capecitabine,
Acquired ceritinib, cesium chloride ◊, crizotinib, dasatinib,
eribulin, fluorouracil, nilotinib, lapatinib, lenvatinib,
Metabolic disorders osimertinib, oxaliplatin, panobinostat, pazopanib,
Hypokalemia ribociclib, romidepsin, sorafenib, sunitinib, tegafur Δ,
toremifene, trifluridine-tipiracil, vandetanib,
Hypomagnesemia
vemurafenib, vorinostat
Hypocalcemia
Analgesic, anesthetic, and sedative drugs
Starvation
Anesthetic/sedative: Chloral hydrate, propofol
Anorexia nervosa
Opioids: Buprenorphine §, hydrocodone,
Liquid protein diets loperamide ¥ (in overdose), methadone
Hypothyroidism Bronchodilators (beta 2 -agonists)
Bradyarrhythmias Arformoterol, albuterol, formoterol, levalbuterol,

indacaterol, olodaterol, salmeterol, terbutaline,
Sinus node dysfunction
vilanterol
Atrioventricular (AV) block – second- or third-degree
Diuretics
Antiarrhythmic drugs
Via electrolyte changes (especially hypokalemia or
Quinidine, procainamide, disopyramide hypomagnesemia)
Flecainide, propafenone Gastrointestinal drugs
Amiodarone ¶, dronedarone, vernakalant Δ Antidiarrheal: Loperamide ¥ (in overdose)
Sotalol Antiemetics: Ondansetron, granisetron, dolasetron,
Dofetilide, ibutilide droperidol (may be safe at the low doses used by
anesthesiologists [0.625 to 1.25 mg]), hydroxyzine,
Antianginal drugs tropisetron Δ
Ranolazine, ivabradine Δ Promotility: Cisapride (restricted availability),
Anticholinergic drugs (antimuscarinics) domperidone Δ, metoclopramide
Solifenacin, tolterodine Proton pump inhibitors: Chronic use leading to

hypomagnesemia (rare)
Anti-infective drugs
Gonadotropin-releasing hormone agonists and
Antimalarial:
antagonists
Known risk: Artemether, artemether-
lumefantrine, chloroquine, halofantrine, Buserelin, degarelix, goserelin, histrelin, leuprolide,
lumefantrine, quinidine triptorelin
Possible or conditional risk: Delamanid Δ, Neurologic drugs

hydroxychloroquine, mefloquine, primaquine,
Apomorphine, deutetrabenazine, donepezil,
quinine
ezogabine, fingolimod, pimavanserin, tetrabenazine
Antituberculous: Bedaquiline Psychotropic drugs
Azole antifungals: Fluconazole, itraconazole, Antipsychotics:
ketoconazole (systemic), posaconazole, voriconazole
Known risk: Chlorpromazine, haloperidol,
Fluoroquinolones (systemic): Ciprofloxacin, levosulpiride Δ, methotrimeprazine
gatifloxacin Δ, levofloxacin, moxifloxacin, ofloxacin, (levomepromazine) Δ, pimozide, sulpiride Δ,
sparfloxacin Δ thioridazine
HIV antiretrovirals: Possible or conditional risk: Amisulpride Δ,

aripiprazole, asenapine, clozapine,
Known risk: Efavirenz, lopinavir, saquinavir
Δ Δ
Possible or conditional risk: Atazanavir, cyamemazine Δ, flupentixol Δ, iloperidone,

nelfinavir, rilpivirine, ritonavir melperone Δ, olanzapine, paliperidone,
perphenazine, pimavanserin, pipamperone Δ,
Macrolide antibiotics: Azithromycin, erythromycin,
quetiapine, risperidone, sertindole Δ, tiapride Δ,
clarithromycin, roxithromycin, telithromycin
ziprasidone
Metronidazole
Tricyclic and tetracyclic antidepressants (TCAs) ‡
Pentamidine (intravenous)
Selective serotonin reuptake inhibitors (lower risk
Pentavalent antimonials than TCAs): Citalopram, escitalopram,
(antiparasitic/antiprotozoal): Meglumine fluoxetine (less than citalopram)
antimoniate, sodium stibogluconate
Others: Atomoxetine, trazodone, valbenazine
Telavancin
Vasodilator drugs
Bepridil ◊, cilostazol
Other drugs and herbs
Miscellaneous: Anagrelide, alfuzosin, cocaine,

eliglustat, mifepristone, papaverine (intracoronary),
pasireotide, probucol ◊, terlipressin Δ
Herbs: Cinchona (contains quinine), licorice extract

(glycyrrhizin) in overuse leading to electrolyte
changes
Other factors
Myocardial ischemia or infarction, especially with

prominent T-wave inversions
Intracranial disease
HIV infection
Hypothermia
Toxic exposure: Organophosphate insecticides
Connective tissue diseases with anti-Ro/SSA

antibodies
This is not a complete list of all QTc prolonging drugs and does not include drugs with either a minor degree
or isolated association(s) with QTc prolongation that appear to be safe in most patients, but may need to be avoided in
patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is
available at the Credible Meds website.
HIV: human immunodeficiency virus; QTc: corrected QT interval.
* The long and growing list of medications and other factors capable of prolonging the QTc represents an evolving area of
clinical research. In some cases of long QTc, two or more factors may be involved.
¶ In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with torsades de pointes (TdP); refer
to accompanying text within UpToDate topic review of acquired long QT syndrome.
Δ Not available in the United States.
◊ Removed from market in most countries due to adverse cardiovascular effects.
§ Although product labeling for buprenorphine analgesics warn of QTc prolongation at doses exceeding those recommended,
data for buprenorphine in usual doses for treatment of opioid use disorder are reassuring, and it appears to be a suitable
alternative for patients with significant QTc prolongation due to methadone. Refer to the UpToDate topic reviews of opioid
intoxication and opioid use disorder for detail.
¥ Over-the-counter; available without a prescription.
‡ Although amoxapine and protriptyline are not included on the AZCERT list of drugs associated with acquired QT
prolongation, overdose of these tricyclic antidepressants has been associated with cardiovascular toxicity and fatalities.
Data from:
1. Nielsen J, Graff C, Kanters J, et al. Assessing QT interval prolongation and its associated risks with antipsychotics. CNS
Drugs 2011; 25:473.
2. Li E, Esterly J, Pohl S, et al. Drug-induced QT interval prolongation: Considerations for clinicians. Pharmacotherapy
2010; 30:684.
3. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at
http://crediblemeds.org/ (Accessed August 8, 2017).
4. Lexicomp Online. Copyright ©1978-2017 Lexicomp, Inc. All Rights Reserved.
Eligibility criteria for medical termination of pregnancy
Pregnancy up to 49 days of gestation
Agreement to undergo surgical abortion if the procedure fails
Absence of a contraindication to surgical abortion
Agreement to complete therapy and all clinic visits
A means of reaching an emergency facility within one hour if problems occur
Legally competent to sign a consent form for obtaining an abortion
Per manufacturer Danco Laboratories.
Types of vaginal bleeding as recorded by women from day 1

(administration of mifepristone) to day 15
The data are from 1506 women who did not undergo surgical termination of
pregnancy and who recorded the types of bleeding they had from study day 1 to day
15 on menstrual diary cards. Bleeding was characterized as spotting, as similar to
normal menstrual bleeding (normal), or as heavier than normal menstrual bleeding
(heavy).
Data from Spitz, IM, Bardin, CW, Benton, L, Robbins, A. N Engl J Med 1998; 388:1241.
Pregnancy termination with mifepristone and oral misoprostol
Time of expulsion of conceptus in 1720 women with

successful medical termination of pregnancy
The women received oral mifepristone 600 mg at visit 1 and oral misoprostol 400 mcg
two days later (visit 2). "Uncertain" indicates that expulsion occurred within the first 24
hours after misoprostol was given, but the exact time was not known.
Data from Spitz, IM, Bardin, CW, Benton, L, Robbins, A. N Engl J Med 1998; 388:1241.
Contributor Disclosures
Bryna Harwood, MD, MS Nothing to disclose Jody Steinauer, MD, MAS Nothing to disclose Sandy J Falk,
MD, FACOG Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

First-Trimester Medication Abortion (Termination of Pregnancy)

Enviado por

Dados do documento

Título original

Direitos autorais

Formatos disponíveis

Compartilhar este documento

Compartilhar ou incorporar documento

Opções de compartilhamento

Você considera este documento útil?

Este conteúdo é inapropriado?

Direitos autorais:

Formatos disponíveis

First-Trimester Medication Abortion (Termination of Pregnancy)

Enviado por

Direitos autorais:

Formatos disponíveis

10/27/2017 First-trimester medication abortion (termination of pregnancy) - UpToDate

Official reprint from UpToDate®

First-trimester medication abortion (termination of pregnancy)

Author: Bryna Harwood, MD, MS

CONTRAINDICATIONS — The manufacturer's list of contraindications to the use of mifepristone and

Medical conditions — Mifepristone is a glucocorticoid receptor antagonist and is therefore contraindicated in

Asthma is not a contraindication to use of misoprostol. Although some prostaglandins result in

● Make an accurate assessment of gestational age

● Diagnose ectopic pregnancy

● Must sign a prescriber's agreement with the manufacturer of mifepristone

● Day one – 200 mg of mifepristone taken by mouth

● Seven to 14 days after taking mifepristone – Follow-up with a clinician

Mifepristone administered alone results in complete termination of pregnancy in 64 to 85 percent of women at

● Misoprostol administration – Misoprostol is self-administered by the patient in a nonclinical setting 24 to 72

Preprocedure evaluation and preparation

If the woman has an intrauterine device in place, it should be removed.

On pelvic ultrasound, absence of a gestational sac is confirmation of a complete abortion. Heterogeneous

First-trimester mifepristone/misoprostol abortion results in an incomplete abortion in 2 to 8 percent of procedures

OUTCOME — First-trimester mifepristone/misoprostol abortion is successful in 92 to 98 percent of procedures

The efficacy varies with several factors:

● Route of administration and dose of misoprostol

Up to 49 days of gestation — The successful completion of medication abortion in pregnancies up to 49 days

ALTERNATIVE MEDICATION METHODS

● Basics topics (see "Patient education: Abortion (The Basics)")

SUMMARY AND RECOMMENDATIONS

● For women undergoing first-trimester mifepristone/misoprostol medication abortion:

• Mifepristone followed in 24 to 72 hours by misoprostol as well as self-administration of misoprostol has

● First-trimester medication is successful in 92 to 98 percent of procedures. Failed medication abortion is

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 3296 Version 21.0

Contraindications to medication abortion

Confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass

Intrauterine device in place

Chronic adrenal failure

Concurrent long-term corticosteroid therapy

Hemorrhagic disorders or concurrent anticoagulant therapy

Guidelines per manufacturer (Danco laboratories).

Graphic 54726 Version 5.0

Cytochrome P450 3A4 (CYP3A4) inhibitors and inducers*

Strong inhibitors Moderate inhibitors Strong inducers Moderate inducers

Boceprevir Aprepitant Enzalutamide Bosentan

Ceritinib Cimetidine ¶ Fosphenytoin Dabrafenib

Clarithromycin Conivaptan Lumacaftor Dexamethasone ¶

Cobicistat and cobicistat Crizotinib Mitotane Efavirenz

Graphic 76992 Version 42.0

Some reported causes and potentiators of the long QT syndrome*

Congenital Acquired (continued)

Hypothyroidism Bronchodilators (beta 2 -agonists)

Bradyarrhythmias Arformoterol, albuterol, formoterol, levalbuterol,

Solifenacin, tolterodine Proton pump inhibitors: Chronic use leading to

Possible or conditional risk: Delamanid Δ, Neurologic drugs

HIV antiretrovirals: Possible or conditional risk: Amisulpride Δ,

Possible or conditional risk: Atazanavir, cyamemazine Δ, flupentixol Δ, iloperidone,

Other drugs and herbs

Miscellaneous: Anagrelide, alfuzosin, cocaine,

Herbs: Cinchona (contains quinine), licorice extract

Myocardial ischemia or infarction, especially with

Toxic exposure: Organophosphate insecticides

Connective tissue diseases with anti-Ro/SSA

4. Lexicomp Online. Copyright ©1978-2017 Lexicomp, Inc. All Rights Reserved.

Graphic 57431 Version 79.0

Eligibility criteria for medical termination of pregnancy

Pregnancy up to 49 days of gestation