A Prospective Randomized Comparison Trial on the Use of Mifepristone With Sublingual or Buccal Misoprostol for Medical Abortions of Less Than 9 Weeks Gestation
A Prospective Randomized Comparison Trial on the Use of Mifepristone With Sublingual or Buccal Misoprostol for Medical Abortions of Less Than 9 Weeks Gestation
The primary objective of this study is to compare the incidence of side effects of buccal and
 sublingual misoprostol when combined with mifepristone for medical abortions of less than 9
 weeks gestation. The secondary outcome is to compare the complete abortion rate and
 induction-abortion interval between the two methods of administration of misoprostol.
After mifepristone was approved by the United States Food and Drug Administration in 2000,
 the combination of mifepristone 200 mg and vaginal use of misoprostol 800 mcg became almost a
 standard of care in early medical abortion up to 63 days of gestation. When combined with
 mifepristone for medical abortion in the first trimester, vaginal administration of
 misoprostol is more effective, faster, and has a lower rate of ongoing pregnancy, and fewer
 gastrointestinal side effects than oral misoprostol.

 Although misoprostol is more effective when given vaginally, most women prefer the oral route
 because this can avoid the uncomfortable vaginal examination and provide more privacy during
 medical induction. Another concern about vaginal administration is the potential risk of
 infection. In late March 2006, analyses of serious uterine infections following medical
 abortions by a regimen of oral mifepristone followed by vaginal misoprostol led Planned
 Parenthood Federation of America health centres to change the route of misoprostol
 administration. Given these concerns, alternative administration via sublingual (holding
 pills under the tongue) and buccal (holding pills in the cheek) routes have been
 investigated, as the misoprostol is absorbed directly and avoids the gastrointestinal system
 similar to vaginal administration.

 A pharmacokinetic study showed that sublingual administration of misoprostol resulted in the
 greatest bioavailability when compared with oral or vaginal administration. In a randomized,
 cross-over pharmacokinetic study of 10 women by Schaff and colleagues of sublingual versus
 buccal misoprostol 800 mcg, the mean misoprostol plasma concentration-time curves at 4 hours
 and the maximum concentration were significantly higher for sublingual administration than
 the buccal route. However, buccal misoprostol administration resulted in fewer symptoms and
 was found to be more acceptable by women.

 Buccal misoprostol 800 mcg after mifepristone 200 mg for terminating pregnancy through 63
 days of gestation has a higher success rate and less ongoing pregnancy when compared with
 oral misoprostol, especially in pregnancies of 57-63 days. Adverse effect profiles were
 similar, although fever and chills were reported approximately 10% more often among women who
 took buccal misoprostol. When used for abortion through 56 days of gestation, buccal
 administration of misoprostol after mifepristone appears to be a highly effective and
 acceptable alternative compared with vaginal administration, and with similar adverse effects
 profile.

 Medical abortions of less than 9 weeks gestation using sublingual misoprostol 800 mcg after
 mifepristone 200 mg has achieved complete abortion rate of 98.2% but is associated with more
 gastrointestinal side effects, fever, and chills when compared with vaginal route.

 Both buccal and sublingual administration of misoprostol following mifepristone have been
 shown to be effective in inducing first trimester medical abortions, but with different side
 effects profile. No clinical trials have been conducted comparing buccal and sublingual
 administration of misoprostol in first trimester medical abortion. The purpose of the present
 study is to compare the incidence of side effects of buccal and sublingual misoprostol when
 combined with mifepristone.
Inclusion Criteria:

 -  good general health

 -  older than the age of legal consent (i.e. >18 years old)

 -  requesting medical abortion and eligible for abortion

 -  on Day 1 of the study (day of mifepristone administration) the duration of pregnancy
 not more than 63 days as confirmed by pelvic ultrasound examination

 -  intrauterine pregnancy (intrauterine amniotic sac seen in US)

 -  willing to use other than hormonal or intra-uterine contraception until the first
 menses after termination of pregnancy

 -  if treatment fails she agrees to termination of pregnancy with the surgical method

 -  willing and able to participate after the study has been explained

 -  haemoglobin higher than 10g/L

 Exclusion Criteria:

 -  a history or evidence of adrenal pathology, steroid-dependent cancer, porphyria,
 diastolic pressure over 95mm Hg, bronchial asthma, arterial hypotension.

 -  a history or evidence of thrombo-embolism, severe or recurrent liver disease or
 pruritus of pregnancy

 -  the regular use of prescription drugs before admission to the study

 -  the presence of an IUCD in utero

 -  breast-feeding

 -  multiple pregnancies

 -  heavy smokers