Z Geburtshilfe Neonatol 2001; 205(2): 43-48
DOI: 10.1055/s-2001-14819
ORIGINALARBEIT

Georg Thieme Verlag Stuttgart · New York

Nebenwirkungen von Misoprostol beim Einsatz im Rahmen der Schwangerschaft[1]

Side effects of Misoprostol therapy during pregnancyS. Züst, I. Hösli, D. Surbek, W. Holzgreve
  • Universitäts-Frauenklinik Basel
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Zusammenfassung

Hintergrund Der Einsatz von Misoprostol in Gynäkologie und Geburtshilfe ist bereits weit verbreitet, obwohl die offizielle Zulassung durch die entsprechenden Behörden für den gynäkologischen und geburtshilflichen Bereich in der Schweiz wie in Deutschland noch fehlen. Auch fehlen gerade in diesem Bereich noch umfangreiche Studien zu optimalen Dosierungen und Sicherheit. Bei der Anwendung von Misoprostol in Gynäkologie und Geburtshilfe bewegen wir uns daher in einer juristischen Grauzone.

Material Die vorliegende Arbeit soll eine aktuelle Übersicht zur Indikation von Misoprostol in Gynäkologie und Geburtshilfe, Dosierungen des Medikamentes und seine Nebenwirkungen geben.
Die Indikationen in Gynäkologie und Geburtshilfe sind:
1. Abortinduktion im ersten/zweiten Trimester (bis zur 22. SSW)
2. Zervix-Priming/Weheninduktion im dritten Trimenon (ab 36. SSW)
3. Prävention und Therapie von postpartaler Hämorrhagie

Ergebnisse Misoprostol ist unbestritten ein effektives Medikament, sowohl was die Geburtsinduktion bei intakter Schwangerschaft am Termin oder die Tonisierung des Uterus in der Plazentarperiode anbelangt, aber auch die Möglichkeit der Abortinduktion im I./II. Trimenon betrifft. Dies wurde in mehreren randomisierten Studien ermittelt.

Zunehmend werden jedoch die Nebenwirkungen dieses Medikaments erfasst und diskutiert. Allen voran die Uterusruptur und die fraglich erhöhte perinatale Morbidität im Falle eines Hyperstimulationssyndroms.

Schlussfolgerung Absolut kontraindiziert ist der Einsatz im ambulanten Bereich zur Weheninduktion am Termin aufgrund der inadäquaten Überwachung.

Solange nicht alle kritischen Fragen eindeutig beantwortet werden können, sollte das Medikament nur unter klinischen Bedingungen eingesetzt werden.

Background Although Misoprostol is an already widely used medication in gynecology and obstetrics, extended studies on dosage and safety are still missing. As far as the application of Misoprostol in gynecology and obstetrics is concerned, we are moving between legality and illegality, because in countries like Switzerland and Germany this drug wasn't officially approved for obstetric-gynecologic indications yet.

Materials The aim of the recent work is to give an overview on the indications of Misoprostol in gynecology and obstetrics, the dosages and side effects.
Indications are as follows:
1. induction of abortion in the first and second trimester (maximum up to the 22nd week of gestation)
2. cervical ripening and induction of labour in the third trimester (from 36th week of gestation)
3. prevention and therapy of postpartal hemorrhage

Results There is no doubt that Misoprostol is an efficient drug for both the obstetrical management at the end of normal pregnancy and the third stage labour as well as termination of pregnancy and induction of abortion in the first and second trimester of pregnancy. This has been concluded from many randomized trials.

The side effects of this drug however, have become more obvious over time, especially uterine rupture and the probably elevated perinatal morbidity secondary to the hyperstimulation syndrome.

Conclusions The application of Misoprostol for labour induction in an outpatient setting is absolutely contraindicated.

As long as not all critical questions are answered conclusively, this beneficial drug should only be applied under hospital conditions with close surveillance.

01 Eingang: 13. 6. 2000
Angenommen nach Revision: 21. 8. 2000

Literatur

01 Eingang: 13. 6. 2000
Angenommen nach Revision: 21. 8. 2000

  • 01 Senior  J, Marshall  K, Sangha  R, Clayton  J K. In vitro characterisation of prostanoid receptors on human myometrium at term pregnancy.  Br J Pharm. 1993;;  108 501-506
  • 02 Zieman  M, Fong  S K, Benowitz  N L, Banskter  D, Darney  P D. Absorption kinetics of misoprostol with oral or vaginal administration.  Obstet Gynecol. 1997;;  90 88-92
  • 03 O'Brien  P, El-Refaey  H, Gordon  A, Geary  M, Rodeck  C H. Rectally administered misoprostol for the treatment of postpartum hemorrhage unresponsive to oxytocin and ergometrine: a descriptive study.  Obstet Gynecol. 1998;;  92 212-214
  • 04 Bamigboye  A A, Merrell  D A, Hofmeyr  G R. Randomized comparison of rectal misoprostol with Syntometrine for management of third stage labor.  Acta Obstet Gynecol Scand. 1998;;  77 178-181
  • 05 Bamigboye  A A, Hofmeyr  G R, Merrell  D A. Rectal misoprostol in the prevention of postpartum hemorrhage: a placebo-controlled trial.  Am J Obstet Gynecol. 1998;;  179 1043-1046
  • 06 Norman  J E, Thong  K J, Baird  D T. Uterine contractility and induction of abortion in early pregnancy by misoprostol and mifepristone.  Lancet. 1991;;  338 1233-1236
  • 07 Costa  S H, Vessey  M P. Misoprostol and illegal abortion in Rio de Janeiro, Brazil.  Lancet. 1993;;  341 1258-1261
  • 08 Gonzales  C H, Vargas  F R, Perez  A B et al. Limb deficiency with or without Mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy.  Am J Med Genet. 1993;;  47 59-64
  • 09 Pastuszak  A L, Schuler  L, Speck-Martins  C E, Coelho  K E et al. Use of misoprostol during pregnancy and Mobius' syndrome in infants.  N Engl J Med. 1998;;  338 1881-1885
  • 10 Gonzales  C H, Marques-Dias  M J, Kim  C A et al. Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy.  Lancet. 1998;;  351 1624-1627
  • 11 Fonesca  W, Alencar  A JC, Mota  F SB, Coelho  H LL. Misoprostol and congenital malformations.  Lancet. 1991;;  338 56
  • 12 Cabezas  E. Medical versus surgical abortion.  Int J Gynecol Obstet. 1999;;  63 141-146
  • 13 Wu  S. Medical. Medical abortion in China.  J Am Medl Womens Assoc. 2000;;  55 (3 Suppl) 197-199, 204
  • 14 Hofmeyr  G J. Misoprostol in obstetrics and gynaecology - unregistered, dangerous and essential. Editorial.  SAMJ. 1998;;  5 535
  • 15 Wong  K S, Ngai  C S, Wong  A Y, Tang  L C, Ho  P C. Vaginal misoprostol compared with vaginal gemeprost in termination of second trimester pregnancy. A randomized trial.  Contraseption. 1998;;  58 207-210
  • 16 Jain  J K, Kuo  J, Mishell  D R Jr. A comparison of two dosing regimens of intravaginal misoprostol for second-trimester pregnancy termination.  Obstet Gynecol. 1999;;  93 571-575
  • 17 Herabutya  Y, O'Prasertsawat  P, Pokpirom  J. A comparison of intravaginal misoprostol and intracervical prostaglandin E2 gel for ripening of unfavourable cervix and labor induction.  J Obstet Gynaecol Res. 1997;;  23 369-374
  • 18 El-Refaey  H, Hinshaw  K, Henshaw  R, Smith  N, Templeton  A. Medical management of missed abortion and anembryonic pregnancy.  BMJ. 1992;;  305 1399
  • 19 El-Refaey  H, Templeton  A. Unsuccessful treatment of missed abortion.  Br J Obstet Gynaecol. 1998;;  105 567-568
  • 20 Nielsen  S, Hahlin  M, Platz-Christensen  J J. Unsuccessful treatment of missed abortion with a combination of an antiprogesterone and a prostaglandin E1 analogue (see comments).  Br J Obstet Gynaecol. 1997;;  104 1094-1096
  • 21 Eng  N S, Guan  A. Comparative study of intravaginal misoprostol with gemeprost as an abortifacient in second trimester missed abortion.  Aust N Z J Obstet Gynaecol. 1997;;  37 331-334
  • 22 Keirse  M JNC. Prostaglandins in preinduction cervical ripening: Meta-analysis of worldwide clinical experience.  J Reprod Med. 1993;;  38 (Suppl) 89-98
  • 23 MacKenzie  I Z, Burns  E. Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 1. Clinical outcome.  Br J Obstet Gynecol. 1997;;  104 1062-1067
  • 24 Hofmeyr  G J, Gülmezoglu  A M, Alfirevic  Z. Misoprostol for induction of labour: a systematic review.  Br J Obstet Gynaecol. 1999;;  106 798-803
  • 25 Egarter  C H, Husslein  P W, Rayburne  W F. Uterine hyperstimulation after low-dose prostaglandin E2 therapy: tocolytic treatment in 181 cases.  Am J Obstet Gynecol. 1990;;  163 794-796
  • 26 Mariani-Neto  C, Leao  E J, Baretto  E M, Kenj  G, De Aquino  M M. Use of misoprostol for labour induction in stillbirths.  Rev Paul Med. 1987;;  105 325-328
  • 27 Mariani-Neto  C, Delbin  A L, Val  R D. Padrao tocografico desencadeado pelo misoprostol.  Rev Paul Med. 1988;;  106 205-208
  • 28 Wing  D A. Labor induction with misoprostol.  Am J Obstet Gynecol. 1999;;  181 339-345
  • 29 Sanchez-Ramos  L, Chen  A H, Kaunitz  A M, Gaudier  F L, Delke  I. Labor induction with intravaginal misoprostol in term premature rupture of membranes: a randomized study.  Obstet Gynecol. 1997;;  89 909-912
  • 30 Wing  D A, Jones  M M, Rahall  A, Goodwin  T M, Paul  R H. A comparison of misoprostol and prostaglandin E2 gel for preinduction cervical ripening and labor induction.  Am J Obstet Gynecol. 1995;  172 1804-1810
  • 31 Wing  D A, Rahall  A, Jones  M M, Goodwin  T M, Paul  R H. Misoprostol: an effective agent for cervical ripening and labor induction.  Am J Obstet Gynecol. 1995;;  172 1811-1816
  • 32 Wing  D A, Paul  R H. A comparison of differing dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and labor induction.  Am J Obstet Gynecol. 1996;;  175 158-164
  • 33 Wing  D A, Ortiz-Omphroy  G, Paul  R H. A comparison of intermittent vaginal administration of misoprostol with continous dinoprostone for cervical ripening and labor induction.  Am J Obstet Gynecol. 1997;;  177 612-618
  • 34 Wing  D A, Paul  R H. Vaginally administered misoprostol (Cytotec) versus the dinoprostone vaginal insert (Cervidil) for preinduction cervical ripening and labor induction.  Am J Obstet Gynecol. 1997;;  176 113
  • 35 Merrel  D A, Koch  M AT. Induction of labour with misoprostol in the second and third trimesters of pregnancy.  S Afr Med J. 1995;;  85 1088-1090
  • 36 Merrel  D A, Koch  M AT, Thomas  P C. Experience with vaginal and rectal misoprostol as an oxytocic agent in pregnancy. In: PAFMACH Conference,. Johannesburg, South Africa; 1996:
  • 37 Surbek  D V, Fehr  P M, Hoesli  I, Holzgreve  W. Oral misoprostol for third stage of labor: a randomized placebo-controlled trial.  Obstet Gynecol. 1999;;  94 255-258
  • 38 Lumbiganon  P, Hofmeyr  J, Gülmezoglu  A M, Pinol  A, Villar  J. Misoprostol dose-related shivering and pyrexia in the third stage of labour.  Br J Obstet Gynaecol. 1999;  106 304-308
  • 39 Hofmeyr  G J, Nikodem  V C, de Jager  M, Gelbart  B R. A randomised placebo controlled trial of oral misoprostol in the third stage of labour.  Br J Obstet Gynaecol. 1998;;  105 971-975
  • 40 El-Refaey  H, O'Brien  P, Morafa  W, Walder  J, Rodeck  C H. Use of oral misoprostol in the prevention of postpartume haemorrhage.  Br J Obstet Gynaecol. 1997;;  104 336-339

Dr. med. Sarah Züst

Universitäts-Frauenklinik

Schanzenstr. 46

4031 Basel

Schweiz