Misoprostol

(BAN, USAN, rINN)
Misoprostol Chemical formula
Synonyms: Misoprostoli; Misoprostolum; Mizoprostol; SC-29333. (±)-Methyl 7-{(1R,2R,3R)-3-hydroxy-2-[(E)-(4RS)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopentyl}heptanoate; (±)-Methyl (13E)11,16-dihydroxy-16-methyl-9-oxoprost-13-enoate.
Cyrillic synonym: Мизопростол.

💊 Chemical information

Chemical formula: C22H38O5 = 382.5.
CAS — 59122-46-2.
ATC — A02BB01; G02AD06.
ATC Vet — QA02BB01; QG02AD06.

Pharmacopoeias.

In Eur..

Ph. Eur. 6.2

(Misoprostol). A clear, colourless or yellowish, hygroscopic, oily liquid. Practically insoluble in water; soluble in alcohol; sparingly soluble in acetonitrile. Store in airtight containers at −20°.

💊 Adverse Effects

The commonest adverse effect of misoprostol is diarrhoea. Other gastrointestinal effects include abdominal pain, dyspepsia, flatulence, and nausea and vomiting. Increased uterine contractility and abnormal vaginal bleeding (including menorrhagia and intermenstrual bleeding) have been reported. Other adverse effects include skin rashes, headache, and dizziness. Hypotension is rarely seen at doses recommended for peptic ulcer disease.

Incidence of adverse effects.

Data on misoprostol presented to the FDA have been summarised.1 During controlled studies the most common adverse effect was diarrhoea (8.2% compared with 3.1% for placebo); it was dose-related but usually mild, only 8 of 2003 subjects receiving misoprostol having withdrawn because of incapacitating diarrhoea. Headaches and abdominal discomfort were also reported. The effects of misoprostol on the uterus and the potential risks of uterine bleeding or abortion in pregnant women were of more concern. In nonpregnant women taking part in the controlled studies there were menstrual complaints in 15 of 410 (3.7%) receiving misoprostol compared with 2 of 115 (1.7%) given placebo. In a study in pregnant women who had elected to undergo first trimester abortion, all 6 who had a spontaneous expulsion of the uterine contents had received 1 or 2 doses of misoprostol 400 micrograms the previous evening, while none of those given placebo aborted spontaneously; overall 25 of the 56 women given misoprostol had uterine bleeding compared with only 2 of 55 on placebo.
1. Lewis JH. Summary of the 29th meeting of the Gastrointestinal Drugs Advisory Committee, Food and Drug Administration— June 10, 1985. Am J Gastroenterol 1985; 80: 743–5.

Effects on the fetus.

Misoprostol on its own is only a weak abortifacient and is often ineffective when used alone for the termination of pregnancy (see below). However, it has been widely misused for this purpose in some countries, notably Brazil,1,2 and anecdotal reports have associated congenital malformations with such misuse during the first trimester of pregnancy. A systematic review3 of 4 case-control studies confirmed that misoprostol was associated with an increased risk of congenital abnormality, particularly Möbius syndrome and terminal transverse limb defects.
1. Costa SH, Vessey MP. Misoprostol and illegal abortion in Rio de Janeiro, Brazil. Lancet 1993; 341: 1258–61
2. Coêlho HLL, et al. Misoprostol and illegal abortion in Fortaleza, Brazil. Lancet 1993; 341: 1261–3. Correction. ibid.; 1486
3. da Silva Dal Pizzol T, et al. Prenatal exposure to misoprostol and congenital anomalies: systematic review and meta-analysis. Reprod Toxicol 2006; 22: 666–71.

Effects on the uterus.

For reference to uterine rupture in women given misoprostol to induce labour or terminate pregnancy, see under Dinoprostone.

Toxic shock syndrome.

Fatal toxic shock syndrome has occurred in a few women who underwent medical termination of pregnancy using oral mifepristone and vaginal misoprostol, although a causal relationship between these drugs and the deaths has not been established.

💊 Precautions

Misoprostol should not be used to treat peptic ulcer disease in patients who are pregnant or who may become pregnant because it can cause uterine contraction. It should be used with caution in patients in whom hypotension might cause severe complications. Patients with conditions such as inflammatory bowel disease, for whom profound diarrhoea could be dangerous, should be monitored carefully if misoprostol is given. Like other prostaglandins used in the termination of pregnancy, misoprostol should not be used in women at increased risk of uterine rupture, such as those with multiple pregnancy or a uterus scarred by previous caesarean section. Once a prostaglandin has been given to terminate pregnancy it is essential that termination take place; if the prostaglandin is unsuccessful other measures should be used.

Breast feeding.

Misoprostol acid was detected in the breast milk of 10 women given a single oral dose of misoprostol for postpartum uterine atony.1 The concentration rose rapidly, peaked at about 1 hour, and had fallen towards the detection limit by about 5 hours after the dose. Product information for misoprostol licensed for use in gastric ulceration advises that it should not be given to breast-feeding women because misoprostol acid could potentially cause diarrhoea in the infant.
1. Vogel D, et al. Misoprostol versus methylergometrine: pharmacokinetics in human milk. Am J Obstet Gynecol 2004; 191: 2168–73.

Inflammatory bowel disease.

Life-threatening diarrhoea was reported in a patient with unrecognised Crohn’s disease after 6 doses of misoprostol.1 Abdominal cramps, pain, and profuse watery diarrhoea also occurred after 3 doses of misoprostol in a woman with Crohn’s disease.2 In a cohort study of misoprostol taken with NSAIDs for arthritis there were 13 patients with a history of inflammatory bowel disease; 7 did not develop diarrhoea, 3 developed mild diarrhoea, 1 developed severe diarrhoea that stopped when misoprostol was withdrawn, and 2 developed bloody diarrhoea.3
1. Kornbluth A, et al. Life-threatening diarrhea after short-term misoprostol use in a patient with Crohn ileocolitis. Ann Intern Med 1990; 113: 474–5
2. Johnson JS, et al. Profuse diarrhea after misoprostol use in a patient with a history of Crohn’s disease. Ann Pharmacother 1992; 26: 1092–3
3. Faich GA, et al. Diarrhea after misoprostol in Crohn disease. Ann Intern Med 1991; 114: 342.

💊 Interactions

NSAIDs.

It has been suggested that aspirin and NSAIDs, which are prostaglandin synthetase inhibitors, might alter the efficacy of misoprostol used for termination of pregnancy by inhibiting uterine cramping. However, studies in women undergoing medical1 or surgical2 termination found that NSAIDs did not reduce the efficacy of misoprostol. In another study,3 diclofenac did not reduce the efficacy of medical termination using mifepristone followed by misoprostol.
1. Creinin MD, Shulman T. Effect of nonsteroidal anti-inflammatory drugs on the action of misoprostol in a regimen for early abortion. Contraception 1997; 56: 165–8
2. Li CFI, et al. A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy. Contraception 2003; 67: 101–5. Correction. ibid.; 339
3. Fiala C, et al. The effect of non-steroidal anti-inflammatory drugs on medical abortion with mifepristone and misoprostol at 13–22 weeks gestation. Hum Reprod 2005; 20: 3072–7.

💊 Pharmacokinetics

Misoprostol is reported to be rapidly absorbed and metabolised to its active form (misoprostol acid; SC30695) after oral doses; peak plasma concentrations of misoprostol acid occur after about 15 to 30 minutes. Food reduces the rate but not the extent of absorption. Misoprostol acid is further metabolised by oxidation in a number of body organs and is excreted mainly in the urine. The plasma elimination half-life is reported to be between 20 and 40 minutes. Misoprostol acid is distributed into breast milk.
1. Schoenhard G, et al. Metabolism and pharmacokinetic studies of misoprostol. Dig Dis Sci 1985; 30 (suppl): 126S–128S
2. Karim A, et al. Effects of food and antacid on oral absorption of misoprostol, a synthetic prostaglandin E analog. J Clin Pharmacol 1989; 29: 439–43
3. Foote EF, et al. Disposition of misoprostol and its active metabolite in patients with normal and impaired renal function. J Clin Pharmacol 1995; 35: 384–9
4. Zieman M, et al. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol 1997; 90: 88–92
5. Khan R-U, El-Refaey H. Pharmacokinetics and adverse-effect profile of rectally administered misoprostol in the third stage of labor. Obstet Gynecol 2003; 101: 968–74
6. Khan R-U, et al. Oral, rectal, and vaginal pharmacokinetics of misoprostol. Obstet Gynecol 2004; 103: 866–70
7. Schaff EA, et al. Comparison of misoprostol plasma concentrations following buccal and sublingual administration. Contraception 2005; 71: 22–5.

💊 Uses and Administration

Misoprostol is a synthetic analogue of alprostadil. It is used in the treatment of benign gastric and duodenal ulceration (below) including that associated with NSAIDs. The usual oral dose is 800 micrograms daily in two to four divided doses with food. Treatment is initially given for at least 4 weeks, even if symptoms are relieved sooner, and may continue for up to 8 weeks if necessary. Further courses may be used to treat relapse. Misoprostol is also used prophylactically with NSAIDs to prevent NSAID-induced ulcers. The usual oral dose is 200 micrograms two to four times daily. A dose of 100 micrograms four times daily may be used in patients not tolerating the higher dose. Some preparations of NSAIDs contain misoprostol in an attempt to limit their adverse effects on the gastrointestinal mucosa. Misoprostol may be used to ripen the cervix before surgical termination of pregnancy (below) in the first trimester. A single oral dose of misoprostol 400 micrograms is given 3 to 4 hours before surgery. It may also be used for medical termination of pregnancy at up to 49 days of amenorrhoea, in a single oral dose of 400 micrograms given 36 to 48 hours after mifepristone. Misoprostol has also been used for induction of labour and in the management of postpartum haemorrhage (see below).
1. Goldberg AB, et al. Misoprostol and pregnancy. N Engl J Med 2000; 344: 38–47
2. Blanchard K, et al. Misoprostol for women’s health: a review. Obstet Gynecol 2002; 99: 316–32
3. Lokugamage AU, et al. Misoprostol and pregnancy: ever-increasing indications of effective usage. Curr Opin Obstet Gynecol 2003; 15: 513–18
4. Chong YS, et al. Misoprostol: a quarter century of use, abuse, and creative misuse. Obstet Gynecol Surv 2004; 59: 128–40.

Labour induction and augmentation.

Prostaglandins are well established for the induction of labour and misoprostol has been widely investigated for this indication. A systematic review1 of studies of misoprostol given vaginally found that it increased cervical ripening and induced labour. It was more effective than vaginal or intracervical dinoprostone, reducing the need for oxytocin augmentation and improving the rate of vaginal delivery achieved within 24 hours. It was also found to be more effective than intravenous oxytocin. Most studies used misoprostol tablets in a dose of 50 micrograms vaginally every 4 hours, but reported doses have varied from 25 micrograms every 2 to 3 hours, to 100 micrograms every 6 to 12 hours. Low doses of misoprostol resulted in more use of oxytocin, but caused less uterine hyperstimulation. Although unlicensed, misoprostol is reported to be used outside clinical studies particularly in the USA, and the American College of Obstetricians and Gynecologists has recommended a dose of 25 micrograms intravaginally every 3 to 6 hours.2 Misoprostol has also been given orally but this route is less well established. A wide range of doses have been reported but most studies have used 50 micrograms every 4 hours. Some reviews have found oral to be less effective than vaginal misoprostol.2,3 However, others4 have concluded that oral use produces similar outcomes to vaginal misoprostol, with less hyperstimulation, but that comparison is complicated by the wide variation in doses. Overall, oral misoprostol appears to be at least as effective as vaginal dinoprostone, but because of limited data it should be used with caution.4 The risk of uterine hyperstimulation may be increased with misoprostol by either route, particularly at higher doses,1,4 and it should not be used in women with scarred uteri from previous caesarean delivery or uterine surgery2. There has also been some limited investigation of misoprostol given sublingually.3,5,6 Misoprostol has been tried for labour induction after intra-uterine fetal death, generally in higher doses than those used for labour at term. It has been used successfully in doses of 400 micrograms every 4 hours orally7 and 400 micrograms every 12 hours vaginally.8 A comparison of 200 micrograms given either orally or vaginally every 6 hours, to a maximum of 4 doses or until labour was established, found the time from induction to delivery to be shorter, and fewer women needed oxytocin augmentation, with vaginal use.9 Misoprostol may also be used for active management of the third stage of labour (see Postpartum Haemorrhage, below).
1. Hofmeyr GJ, Gülmezoglu AM. Vaginal misoprostol for cervical ripening and induction of labour. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2003 (accessed 30/06/08)
2. Wing DA. A benefit-risk assessment of misoprostol for cervical ripening and labour induction. Drug Safety 2002; 25: 665–76
3. Bartusevicius A, et al. Oral, vaginal and sublingual misoprostol for induction of labor. Int J Gynecol Obstet 2005; 91: 2–9
4. Alfirevic Z, Weeks A. Oral misoprostol for induction of labour. Available in The Cochrane Database of Systematic Reviews; Issu
2. Chichester: John Wiley; 2006 (accessed 30/06/08)
5. Shetty A, et al. Sublingual misoprostol for the induction of labor at term. Am J Obstet Gynecol 2002; 186: 72–6
6. Shetty A, et al. Sublingual compared with oral misoprostol in term labour induction: a randomised controlled trial. Br J Obstet Gynaecol 2002; 109: 645–50
7. Pongsatha S, Tongsong T. Therapeutic termination of second trimester pregnancies with intrauterine fetal death with 400 micrograms of oral misoprostol. J Obstet Gynaecol Res 2004; 30: 217–20
8. Fawole AO, et al. Experience with intravaginal misoprostol in the management of intra-uterine fetal death. Afr J Med Med Sci 2004; 33: 105–8
9. Nyende L, et al. Comparison of vaginal and oral misoprostol, for the induction of labour in women with intra-uterine foetal death. East Afr Med J 2004; 81: 179–82.

Organ and tissue transplantation.

Misoprostol 200 micrograms orally four times daily improved renal function in ciclosporin-treated recipients of renal transplants.1 The number of patients who had acute graft rejection was lower in the misoprostol group than in the placebo group. However, another study2 did not indicate any difference in the incidence of rejection episodes or in renal function when misoprostol was added to immunosuppressant regimens for kidney transplantation, and misoprostol does not appear to have gained a role in the usual management of renal transplantation.
1. Moran M, et al. Prevention of acute graft rejection by the prostaglandin E analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone. N Engl J Med 1990; 322: 1183–8
2. Pouteil-Noble C, et al. Misoprostol in renal transplant recipients: a prospective, randomized, controlled study on the prevention of acute rejection episodes and cyclosporin A nephrotoxicity. Nephrol Dial Transplant 1994; 9: 552–5.

Peptic ulcer disease.

Misoprostol is used in the prophylaxis and treatment of peptic ulceration in patients taking NSAIDs. There is good evidence that misoprostol can reduce the risk of gastric and duodenal ulcer formation in patients on longterm NSAID treatment,1-4 and it appears more effective in this respect than histamine H2-antagonists,1 for which evidence of benefit against gastric injury is less persuasive. However, misoprostol’s abdominal adverse effects, particularly diarrhoea and abdominal cramps, may limit its usefulness and patient acceptability. Omeprazole, which is equally effective in preventing NSAID-induced ulceration, is better tolerated.3 Improved formulations, in which the active isomer of misoprostol is bound to a polymer, may reduce adverse effects.5
1. Koch M, et al. Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury: a meta-analysis of randomized controlled clinical trials. Arch Intern Med 1996; 156: 2321–32
2. Champion GD, et al. NSAID-induced gastrointestinal damage: epidemiology, risk and prevention, with an evaluation of the role of misoprostol: an Asia-Pacific perspective and consensus. Drugs 1997; 53: 6–19
3. Hawkey CJ, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338: 727–34
4. Rostom A, et al. Prevention of NSAID-induced gastroduodenal ulcers. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2002 (accessed 30/06/08)
5. Chen D, et al. Stabilization and sustained-release effect of misoprostol with methacrylate copolymer. Int J Pharmaceutics 2000; 203: 141–8.

Postpartum haemorrhage.

Prostaglandins, usually given parenterally, have an accepted role in the management of established postpartum haemorrhage not controlled by oxytocin and ergot preparations. There have been reports1-3 of the successful use of rectal misoprostol to control postpartum haemorrhage, using single doses of 800 or 1000 micrograms. A review4 found that there was some evidence for reduced blood loss with lower doses of misoprostol, and suggested that oral, sublingual, rectal, or a combination of these, might be the most effective routes; possible regimens were 200 to 400 micrograms sublingually or rectally, or similar doses plus 200 micrograms orally. It also suggested that the oral dose of misoprostol should not exceed 600 micrograms because of the risk of hyperpyrexia. There have also been a few cases in which intra-uterine misoprostol 800 micrograms has controlled refractory secondary postpartum haemorrhage.5,6 Misoprostol has also been given immediately after delivery in the active management of third-stage labour. In a study7 of more than 18 500 women treated in hospital, which compared oral misoprostol 600 micrograms with intramuscular or intravenous oxytocin, a higher proportion of women who received misoprostol had blood loss of at least 1000 mL and required additional oxytocics. Misoprostol was also associated with significantly more shivering and pyrexia. The results of this large study suggest that parenteral oxytocin is preferred for active management, but it has been argued that misoprostol may be particularly useful in preventing postpartum haemorrhage in developing countries where there is limited access to healthcare facilities and parenteral oxytocics.8-10 Two placebo-controlled studies have addressed this argument, reporting that oral11 or sublingual12 misoprostol used in rural primary healthcare settings reduced postpartum haemorrhage, particularly severe haemorrhage (1000 mL or more). A systematic review13 concluded that oral misoprostol was less effective than injectable oxytocics in reducing blood loss and the use of additional oxytocics, but that it may be used where no injectable uterotonic is available.
1. O’Brien P, et al. Rectally administered misoprostol for the treatment of postpartum hemorrhage unresponsive to oxytocin and ergometrine: a descriptive study. Obstet Gynecol 1998; 92: 212–4
2. Lokugamage AU, et al. A randomized study comparing rectally administered misoprostol versus Syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage. Acta Obstet Gynecol Scand 2001; 80: 835–9
3. Shojai R, et al. Le misoprostol par voie rectale dans l’hémorragie de la délivrance: rectal misoprostol for postpartum hemorrhage. Gynecol Obstet Fertil 2004; 32: 703–7
4. Hofmeyr GJ, et al. Misoprostol to treat postpartum haemorrhage: a systematic review. BJOG 2005; 112: 547–53
5. Adekanmi OA, et al. Intrauterine misoprostol for the treatment of severe recurrent atonic secondary postpartum haemorrhage. BJOG 2001; 108: 541–2
6. Oboro VO, et al. Intrauterine misoprostol for refractory postpartum hemorrhage. Int J Gynecol Obstet 2003; 80: 67–8
7. Gülmezoglu AM, et al. WHO multicentre randomised trial of misoprostol in the management of the third stage of labour. Lancet 2001; 358: 689–95
8. Darney PD. Misoprostol: a boon to safe motherhood...or not? Lancet 2001; 358: 682–3
9. Shannon C, Winikoff B. Use of misoprostol in third stage of labour. Lancet 2002; 359: 709
10. Langenbach C. Misoprostol in preventing postpartum hemorrhage: a meta-analysis. Int J Gynecol Obstet 2006; 92: 10–18
11. Derman RJ, et al. Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial. Lancet 2006; 368: 1248–53
12. Høj L, et al. Effect of sublingual misoprostol on severe postpartum haemorrhage in a primary health centre in Guinea-Bissau: randomised double blind clinical trial. Abridged version: BMJ 2005; 331: 723–7. Full version: http://www.bmj.com/cgi/ content/full/331/7519/723 (accessed 30/06/08
13. Gülmezoglu AM, et al. Prostaglandins for preventing postpartum haemorrhage. Available in The Cochrane Database of Systematic Reviews; Issu
3. Chichester: John Wiley; 2007 (accessed 30/06/08).

Termination of pregnancy.

Prostaglandins are widely used for the termination of pregnancy and misoprostol has been studied both for cervical preparation and for inducing uterine contractions. In the first trimester, misoprostol is used for cervical ripening before surgical termination; it has been reported to be effective when given orally, sublingually, or vaginally,1-4 usually in a dose of 400 micrograms. Oral misoprostol (400 micrograms) given after mifepristone is effective in medical termination of early pregnancy of up to 63 days, and especially so at up to 49 days.5,6Misoprostol 800 micrograms has also been given vaginally after mifepristone,7-10 and a regimen of 2 or 3 doses of sublingual misoprostol after oral mifepristone has been reported to be effective.11 Successful use of vaginal misoprostol with intramuscular or oral methotrexate has also been described.12-15 Misoprostol on its own is only a weak abortifacient, particularly when given orally, and congenital malformations have been reported after failed abortion attempts using misoprostol alone (see Effects on the Fetus, above). However, there is interest in finding a regimen that is effective, particularly in countries where mifepristone is unavailable. A dose of 800 micrograms vaginally, repeated after 24 hours, has been suggested for pregnancy of up to 63 days.16,17 A large study18 has also reported that 800 micrograms given every 12 hours for 3 doses was less effective when given sublingually than vaginally; the routes were equally effective when misoprostol was given every 3 hours, but sublingual administration caused more adverse effects such as fever, chills, shivering, and diarrhoea. Misoprostol has also been studied for termination of pregnancy during the second trimester. It has been used in various regimens to induce medical termination, given either alone19,20 or after oral mifepristone,21,22 and reported to be effective when given vaginally, sublingually, or orally. The time to complete abortion may depend on the dose, dosage interval, and route of administration. Compared with other prostaglandins, intravaginal misoprostol alone (generally as a single dose of 200 micrograms or repeated after 12 hours if necessary) has been reported to be as effective as dinoprostone for medical termination.23 Another study24found 400 micrograms intravaginally every 3 hours, up to 5 doses, to be at least as effective as intra-amniotic carboprost. The use of buccal misoprostol to prepare the cervix before surgical termination has also been described.25 In the management of first trimester pregnancy failure, intravaginal misoprostol has been proposed as an alternative to surgery for evacuation of the uterus.26 Doses have ranged from 400 to 800 micrograms, but the lower doses tend to be less effective.27Misoprostol has also been used with mifepristone for uterine evacuation after pregnancy failure and to induce labour where late intra-uterine fetal death has occurred.
1. Ngai SW, et al. The use of misoprostol for pre-operative cervical dilatation prior to vacuum aspiration: a randomized trial. Hum Reprod 1999; 14: 2139–42
2. Saxena P, et al. Comparison between the sublingual and oral route of misoprostol for pre-abortion cervical priming in first trimester abortions. Hum Reprod 2004; 19: 77–80
3. Vimala N, et al. Cervical priming with sublingual misoprostol vs. 15-methyl-prostaglandin F2α prior to surgical abortion. Int J Gynecol Obstet 2005; 88: 134–7
4. Carbonell Esteve JL, et al. Sublingual versus vaginal misoprostol (400 μg) for cervical priming in first-trimester abortion: a randomized trial. Contraception 2006; 74: 328–33
5. Peyron R, et al. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Engl J Med 1993; 328: 1509–13
6. Spitz IM, et al. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1998; 338: 1241–7
7. El-Refaey H, et al. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med 1995; 332: 983–7
8. Ashok PW, et al. Termination of pregnancy at 9-13 weeks’ amenorrhoea with mifepristone and misoprostol. Lancet 1998; 52: 542–3
9. Schaff EA, et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: a randomized trial. JAMA 2000; 284: 1948–53
10. Shannon C, et al. Regimens of misoprostol with mifepristone for early medical abortion: a randomised trial. BJOG 2006; 113: 621–8
11. Hamoda H, et al. A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation. BJOG 2005; 112: 1102–8
12. Creinin MD, et al. Medical abortion with oral methotrexate and vaginal misoprostol. Obstet Gynecol 1997; 90: 611–16
13. Carbonell JLL, et al. Oral methotrexate and vaginal misoprostol for early abortion. Contraception 1998; 57: 83–8
14. Borgatta L, et al. Early medical abortion with methotrexate and misoprostol. Obstet Gynecol 2001; 97: 11–16
15. Aldrich T, Winikoff B. Does methotrexate confer a significant advantage over misoprostol alone for early medical abortion? A retrospective analysis of 8678 abortions. BJOG 2007; 114: 555–62
16. Philip NM, et al. A consensus regimen for early abortion with misoprostol. Int J Gynecol Obstet 2004; 87: 281–3
17. Blanchard K, et al. Misoprostol alone for early abortion: an evaluation of seven potential regimens. Contraception 2005; 72: 91–7
18. von Hertzen H, et al. WHO Research Group on Postovulatory Methods of Fertility Regulation. Efficacy of two intervals and two routes of administration of misoprostol for termination of early pregnancy: a randomised controlled equivalence trial. Lancet 2007; 369: 1938–46
19. Tang OS, et al. A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy. BJOG 2004; 111: 1001–5
20. Caliskan E, et al. Randomized comparison of 3 misoprostol protocols for abortion induction at 13–20 weeks of gestation. J Reprod Med 2005; 50: 173–80. Correction. ibid.; 732. [dose
21. Hamoda H, et al. A randomized trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion at 13–20 weeks gestation. Hum Reprod 2005; 20: 2348–54
22. Tang OS, et al. A prospective randomized comparison of sublingual and oral misoprostol when combined with mifepristone for medical abortion at 12–20 weeks gestation. Hum Reprod 2005; 20: 3062–6
23. Jain JK, Mishell DR. A comparison of intravaginal misoprostol with prostaglandin E for termination of second-trimester pregnancy. N Engl J Med 1994; 331: 290–3
24. Su L-L, et al. A prospective, randomized comparison of vaginal misoprostol versus intra-amniotic prostaglandins for midtrimester termination of pregnancy. Am J Obstet Gynecol 2005; 193: 1410–14
25. Patel A, et al. Planned Parenthood Federation of America Buccal Misoprostol Waiver Group. Adequacy and safety of buccal misoprostol for cervical preparation prior to termination of second-trimester pregnancy. Contraception 2006; 73: 420–30
26. Zhang J, et al. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med 2005; 353: 761–9
27. Neilson JP, et al. Medical treatment for early fetal death (less than 24 weeks). Available in The Cochrane Database of Systematic Reviews; Issu
3. Chichester: John Wiley; 2006 (accessed 30/06/08).

💊 Preparations

Proprietary Preparations

Austral.: Cytotec; Austria: Cyprostol; Belg.: Cytotec; Braz.: Cytotec; Canad.: Cytotec†; Chile: Misotrol; Cz.: Cytotec†; Denm.: Cytotec; Fin.: Cytotec; Fr.: Cytotec; Gymiso; Ger.: Cytotec†; Gr.: Cytotec; Hong Kong: Cytotec; India: Cytolog; Misoprost; Indon.: Cytotec; Gastrul; Noprostol; Irl.: Cytotec; Israel: Cytotec; Ital.: Cytotec; Misodex; Malaysia: Cytotec; Mex.: Cytotec; Neth.: Cytotec; Norw.: Cytotec; NZ: Cytotec; Pol.: Cytotec; Port.: Cytotec; Rus.: Cytotec (Сайтотек)†; S.Afr.: Cytotec; Singapore: Cytotec; Spain: Cytotec; Glefos†; Swed.: Cytotec; Switz.: Cytotec; Thai.: Cytotec; Turk.: Cytotec; UK: Cytotec; USA: Cytotec; Venez.: Cytotec. Used as an adjunct in: Arg.: Oxaprost; Austral.: Arthrotec; Austria: Arthrotec; Belg.: Arthrotec; Canad.: Arthrotec; Cz.: Arthrotec†; Denm.: Arthrotec; Fin.: Arthrotec; Fr.: Artotec; Ger.: Arthotec; Gr.: Arthrotec; Hong Kong: Arthrotec; Irl.: Arthrotec; Israel: Arthrotec; Ital.: Artrotec; Misofenac; Mex.: Artrenac Pro; Artrene; Artrotec; Neth.: Arthrotec; Artrotec; Misofenac; Normulen; Norw.: Arthrotec; Pol.: Arthrotec; Port.: Arthrotec; Diclotec; Rus.: Arthrotec (Артротек)†; S.Afr.: Arthrotec; Spain: Artrotec; Normulen; Swed.: Arthrotec; Switz.: Arthrotec; Thai.: Arthrotec†; UK: Arthrotec; Napratec; USA: Arthrotec; Venez.: Arthrotec.
Published November 06, 2018.