Misoprostol

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Misoprostol chemical structure
Misoprostol
Systematic (IUPAC) name
methyl7-[3-hydroxy-2-
(4-hydroxy-4-methyl-oct-1-enyl)-
5-oxo-cyclopentyl]-heptanoate
Identifiers
CAS number 59122-46-2
ATC code A02BB01
PubChem 5282381
DrugBank APRD00037
Chemical data
Formula C22H38O5 
Mol. weight 382.5 g/mol
Pharmacokinetic data
Bioavailability extensively absorbed
Metabolism de-esterified to misoprostol acid, then to prostaglandin F analogs
Half life 20-40 minutes
Excretion Renal:80%
Fecal:15%
Therapeutic considerations
Pregnancy cat.

X
Legal status

℞ Prescription only
Routes Oral, Vaginal, Sublingual

Misoprostol is a drug that is Food and Drug Administration (FDA)-approved for the treatment and prevention of stomach ulcers. It is also used to induce labor and as an abortifacient. It is marketed by G.D. Searle & Company under the trade name Cytotec, but generic versions are available as well.

Chemically, misoprostol is a synthetic prostaglandin E1 (PGE1) analogue.

Contents

[edit] Indicated use

Misoprostol stimulates increased secretion of the protective mucus that lines the gastrointestinal tract and increases mucosal blood flow, thereby increasing mucosal integrity. It is sometimes co-prescribed with non-steroidal anti-inflammatory drugs to prevent their common adverse effect of gastric ulceration (e.g. with Diclofenac in Arthrotec).

[edit] Side effects and contraindications

The most common adverse effects of misoprostol include nausea, vomiting, diarrhea, abdominal pain, chills, shivering, sweating, and fever that can last as long as 3 weeks. Because of its abortifacient properties, it should not be taken by pregnant women.

[edit] Off label uses

[edit] Obstetric and gynecological

[edit] Labor Induction

Misoprostol is commonly prescribed off-label to cause birth induction by uterine contractions and the ripening (opening) of the cervix. Misoprostol is highly effective and much less expensive than pitocin and cervidil, the FDA-approved drugs for medically necessary labor induction. Trial meta-analysis by the Cochrane Collaboration demonstrates no difference in efficacy or side effects between inductions undertaken with cervidil or misoprostol (when used at the correct dosage).

Concern has been expressed about the overuse / misuse of misoprostol for labor induction. High doses can cause uterine rupture (especially in women who have previously had a caesarean section), fetal death and severe fetal brain damage [1] All induction agents cause uterine contractions - this can affect the blood supply to the fetus, especially if contractions become very frequent. Induction agents therefore need to be used with great care and with close fetal monitoring. One of the problems with induction using prostaglandins (either cervidil or misoprostol) is that once given, the process is difficult to reverse. In contrast, Pitocin (oxytocin - a hormone that also causes contractions) has a half-life of about 10 minutes and is administered via intravenous drip, which can be stopped immediately in the event of adverse reaction. [2] A clinical trial is currently underway to establish a controlled delivery method for misoprostol.[3]

Speeding delivery can be medically necessary when the mother is overdue or at risk because of high blood pressure or diabetes, but critics charge that doctors often rely on induction for "convenience" using drugs to induce labor during office hours rather than letting nature take its course.[4]

The manufacturers of misoprostol have never sought to license misoprostol for labor induction. Recently, however, generic forms of misprostol have become available, and it is now licensed for labor induction in Egypt and Brazil, and a licensed induction product is expected in the UK in 2008.[5] [6]

The American College of Obstetricians and Gynecologists advocates misoprostol for labor inductions, and it is on the WHO essential drug list for labour induction.[7]Other agencies await more evidence as to its safety, including obstetric organizations in Britain, Canada and Scandinavia.[8]

[edit] Abortion

Misoprostol is one of the drugs used for chemical abortions. In many countries it is used in conjunction with mifepristone (RU-486). After mifepristone is taken orally, misoprostol is taken 24-72 hours later causing the expulsion of the fetus and associated matter in approximately 92% of the cases. No large studies have established a protocol for the use of misoprostol alone,[9] and the range of efficacy is 65%-93% depending on sample size, gestational age, and other test variables;[10] Misoprostol alone may be more effective in earlier gestation.[11] The side effects associated with the misoprostol-only regimen are generally much more severe than those associated with the combined regimens. Misoprostol is used for self-induced abortions in Brazil, where black market prices exceed US $100. per dose. Illegal medically-unsupervised misoprostol abortions in Brazil are associated with a lower complication rate than other forms of illegal self-induced abortion, but are still associated with a higher complication rate than legal, medically supervised surgical and chemical abortions. Failed misoprostol abortions are associated with birth defects in some cases. [12] [13][14] [15] [16] Poor immigrant populations in New York have also been observed to use self-administered misoprostol to induce abortions, as this method is much cheaper than a surgical abortion (about $2 per dose).[17]

Misoprostol is sometimes used to treat early fetal death in the absence of spontaneous miscarriage, but further research is needed to establish a a safe, effective protocol. [18] It can also be used to dilate the cervix in preparation for a surgical abortion. Misoprostol is also used to prevent and treat post-partum hemorrhage, but it has more side effects and is less effective than oxytocin for this purpose. [19]

[edit] Erectile dysfunction

A 1998 study found misoprostol to be helpful as a supplement to a vacuum pump (VED) in the treatment of erectile dysfunction, but not effective by itself.[20] The paper concluded "The intraurethral application of misoprostol significantly improves the quality of VED-induced erections. This agent seems to be a cheap intraurethral adjunct to VED with mild to moderate local side-effects".

[edit] References

  1. ^ Labor Induction Drug Under Fire. CBS News. Retrieved on 2006-08-22.
  2. ^ Ina May Gaskin (July 11, 2000). Cytotec: Dangerous Experiment or Panacea. Salon.com. Retrieved on 2006-09-08.
  3. ^ Clinical Trial Description at clinicaltrials.gov. Information on Clinical Trials and Human Research Studies. NIH (August, 2006). Retrieved on 2006-08-29.
  4. ^ Goodman, David (2001). Forced Labor. Mother Jones.
  5. ^ Misoprostol.org. Misoprostol.org website.
  6. ^ Alliance Pharmaceuticals. Labour Induction website.
  7. ^ WHO. WHO Essential drug list 2005 section 22.1 website.
  8. ^ Marsden Wagner (Fall 2003). "Cytotec Induction and Off-Label Use". Midwifery Today (Issue 67).
  9. ^ Annotated Bibiography on Misoprostol Alone for Early Abortion. Gynuity Health Projects. Retrieved on 2006-08-22.
  10. ^ Medication Abortion: Misoprostol Alone. Ibis. Retrieved on 2006-09-08.
  11. ^ Instructions for Use: Abortion Induction with Misoprostol in Pregnancies up to 9 Weeks LMP (PDF). Gynuity Health Projects (2003). Retrieved on 2006-08-24.
  12. ^ Corta, SH et al (1993). "Misoprostol and illegal abortion in Rio de Janeiro, Brazil". Lancet 15 (341). PMID 8098402.
  13. ^ Coelho, HL et al (1994). "Misoprostol: the experience of women in Fortaleza, Brazil". Contraception 49 (2). PMID 8143449.
  14. ^ Barbosa, RM (1993). "The Brazilian Experience with Cytotec". Stud Fam Plann 24 (4): 236-40. PMID 8212093.
  15. ^ Rocha, J et al (1994). "Brazil investigates drug's possible link with birth defects". BMJ 309 (6957). PMID 7950553.
  16. ^ Gonzalez, CH et al (1993). "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 47 (1). PMID 8368254.
  17. ^ John Leland: "Abortion Might Outgrow Its Need for Roe v. Wade", The New York Times, October 2, 2005
  18. ^ Neilson JP et al (2006). "Medical treatment for early fetal death (less than 24 weeks)". Cochrane Database Syst Rev 19 (3). PMID 16855990.
  19. ^ J Villar MD et al (2002). Systematic Review of Randomized Controlled Trials of Misoprostol to Prevent Postpartum Hemorrhage. Obstetrics & Gynecology. Retrieved on 2006-09-21.
  20. ^ Ekmekçioğlu, Demirci, Yilmaz & Tatli (1998). "Intraurethral misoprostol: a different agent in the treatment of erectile dysfunction". Sexual Dysfunction 1: 161. DOI:10.1046/j.1460-2679.1998.00030.x.

[edit] External links and further reading

  • Misoprostol from Drugdigest
  • Pro-Life Nation, The New York Times Magazine, April 9, 2006. Reports on the use of Misoprostol in El Salvador, where abortion is illegal in all circumstances.
  • Misoprostol.org a independent website containing dosage guidelines and advice on misoprostol use.
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