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{{Short description|Medication to induce abortion and treat ulcers}}
{{drugbox | verifiedrevid = 408639156
{{Use dmy dates|date=June 2023}}
| IUPAC_name = Methyl 7-((1''R'',2''R'',3''R'')-3-hydroxy-2-((''S,E'')-4-hydroxy-4-methyloct-1-enyl)-5-oxocyclopentyl)heptanoate
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 456483721
| image = Misoprostol.svg | image = Misoprostol.svg
| width = 200
| alt =
| caption =


<!--Clinical data--> <!-- Clinical data -->
| tradename = Cytotec | pronounce =
| tradename = Cytotec, Misodel, others
| Drugs.com = {{drugs.com|monograph|misoprostol}} | Drugs.com = {{drugs.com|monograph|misoprostol}}
| MedlinePlus = a689009 | MedlinePlus = a689009
| DailyMedID = Misoprostol
| pregnancy_category = X
| legal_status = Rx-only | pregnancy_AU = X
| pregnancy_AU_comment = <ref>{{cite web | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2023-PI-01073-1 | title=TGA eBS - Product and Consumer Medicine Information Licence | access-date=14 April 2023 | archive-date=14 April 2023 | archive-url=https://web.archive.org/web/20230414033450/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2023-PI-01073-1 | url-status=live }}</ref><ref>{{cite web | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05416-3 | title=TGA eBS - Product and Consumer Medicine Information Licence | access-date=14 April 2023 | archive-date=14 April 2023 | archive-url=https://web.archive.org/web/20230414031955/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05416-3 | url-status=live }}</ref>
| routes_of_administration = ], ], ]
| pregnancy_category = ]
| routes_of_administration = ], ], ], ]
| class =
| ATCvet =
| ATC_prefix = A02
| ATC_suffix = BB01
| ATC_supplemental = {{ATC|G02|AD06}}

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Angusta (Norgine Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=13 January 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/angusta-norgine-pty-ltd | access-date=9 April 2023 | archive-date=18 March 2023 | archive-url=https://web.archive.org/web/20230318025815/https://www.tga.gov.au/resources/prescription-medicines-registrations/angusta-norgine-pty-ltd | url-status=live }}</ref>
| legal_BR = C1
| legal_BR_comment = Hospital use only<ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-15 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA = Rx-only
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Angusta 25 microgram tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=8 April 2022 | url=https://www.medicines.org.uk/emc/product/12147/smpc | access-date=9 April 2023 | archive-date=10 April 2023 | archive-url=https://web.archive.org/web/20230410051926/https://www.medicines.org.uk/emc/product/12147/smpc | url-status=live }}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref>{{cite web | title=Cytotec- misoprostol tablet | website=DailyMed | date=9 July 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ab12da7-5731-4e06-bf1c-bc3f2e711f12 | access-date=13 April 2023 | archive-date=18 April 2023 | archive-url=https://web.archive.org/web/20230418121539/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ab12da7-5731-4e06-bf1c-bc3f2e711f12 | url-status=live }}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | url=https://www.ema.europa.eu/documents/psusa/misoprostol-gynaecological-indication-labour-induction-list-nationally-authorised-medicinal-products/00010353/202005_en.pdf | title=List of nationally authorised medicinal products. Misoprostol (gastrointestinal indication). Procedure no.: PSUSA/00010353/202005 | publisher=European Medicines Agency | date=14 January 2021 | accessdate=8 August 2021 | archive-date=29 June 2022 | archive-url=https://web.archive.org/web/20220629032409/https://www.ema.europa.eu/en/documents/psusa/misoprostol-gynaecological-indication-labour-induction-list-nationally-authorised-medicinal-products/00010353/202005_en.pdf | url-status=live }}</ref><ref>{{cite web | url=https://www.ema.europa.eu/documents/psusa/misoprostol-gastrointestinal-indication-list-nationally-authorised-medicinal-products-psusa/00010291/202006_en.pdf | title=List of nationally authorised medicinal products. Misoprostol (gastrointestinal indication). Procedure no.: PSUSA/00010291/202006 | publisher=European Medicines Agency | date=14 January 2021 | accessdate=8 August 2021 | archive-date=29 June 2022 | archive-url=https://web.archive.org/web/20220629032409/https://www.ema.europa.eu/en/documents/psusa/misoprostol-gastrointestinal-indication-list-nationally-authorised-medicinal-products-psusa/00010291/202006_en.pdf | url-status=live }}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->
| bioavailability = extensively absorbed | bioavailability = extensively absorbed
| protein_bound = 85% | protein_bound = 80–90% (active metabolite, misoprostol acid)
| metabolism = de-esterified to misoprostol acid, then to prostaglandin F analogs | metabolism = Liver (extensive to misoprostic acid)
| metabolites =
| elimination_half-life = 20&ndash;40 minutes
| onset =
| excretion = ]:80%<br>]:15%
| elimination_half-life = 20–40 minutes
| duration_of_action =
| excretion = Urine (80%)


<!--Identifiers--> <!-- Identifiers -->
| CASNo_Ref = {{cascite|correct|CAS}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 59122-46-2 | CAS_number = 59122-46-2
| ATC_prefix = A02 | CAS_supplemental =
| ATC_suffix = BB01
| PubChem = 5282381 | PubChem = 5282381
| IUPHAR_ligand = 1936 | IUPHAR_ligand = 1936
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| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00419 | KEGG = D00419
| ChEBI =
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 606 | ChEMBL = 606
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =


<!--Chemical data--> <!-- Chemical and physical data -->
| IUPAC_name = Methyl 7-((1''R'',2''R'',3''R'')-3-hydroxy-2-((''S,E'')-4-hydroxy-4-methyloct-1-enyl)-5-oxocyclopentyl)heptanoate
| C=22 | H=38 | O=5
| C=22 | H=38 | O=5
| molecular_weight = 382.534 g/mol
| smiles = O=C1C(O)(/C=C/CC(O)(C)CCCC)1CCCCCCC(=O)OC | SMILES = CCCC(C)(O)C/C=C/1(O)CC(=O)1CCCCCCC(=O)OC
| InChI = 1/C22H38O5/c1-4-5-14-22(2,26)15-10-12-18-17(19(23)16-20(18)24)11-8-6-7-9-13-21(25)27-3/h10,12,17-18,20,24,26H,4-9,11,13-16H2,1-3H3/b12-10+/t17-,18-,20-,22?/m1/s1
| InChIKey = OJLOPKGSLYJEMD-URPKTTJQBH
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H38O5/c1-4-5-14-22(2,26)15-10-12-18-17(19(23)16-20(18)24)11-8-6-7-9-13-21(25)27-3/h10,12,17-18,20,24,26H,4-9,11,13-16H2,1-3H3/b12-10+/t17-,18-,20-,22?/m1/s1 | StdInChI = 1S/C22H38O5/c1-4-5-14-22(2,26)15-10-12-18-17(19(23)16-20(18)24)11-8-6-7-9-13-21(25)27-3/h10,12,17-18,20,24,26H,4-9,11,13-16H2,1-3H3/b12-10+/t17-,18-,20-,22?/m1/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = OJLOPKGSLYJEMD-URPKTTJQSA-N | StdInChIKey = OJLOPKGSLYJEMD-URPKTTJQSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}


<!-- Definition and uses -->
'''Misoprostol''' is a ] that is used for the prevention of non steroidal anti inflammatory drug (]) induced ]s, for early abortion, to treat ], and to ]. The latter use is controversial in the ]. Misoprostol was invented and marketed by ] (now ]) under the trade name '''Cytotec''' (often misspelled '''Cyotec'''), but other ] and ] formulations are now available as well.
'''Misoprostol''' is a synthetic ] medication used to prevent and treat ]s, ], cause an ], and treat ] due to poor contraction of the ].<ref name=Ros2002>{{cite journal | vauthors = Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E, McGowan J | display-authors = 6 | s2cid = 1052260 | title = Prevention of NSAID-induced gastroduodenal ulcers | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD002296 | year = 2002 | volume = 2011 | pmid = 12519573 | doi = 10.1002/14651858.CD002296 | pmc = 8439413 }}</ref><ref name=AHFS2015>{{cite web|title=Misoprostol|url=https://www.drugs.com/monograph/misoprostol.html|publisher=The American Society of Health-System Pharmacists|access-date=20 February 2015|url-status=live|archive-url=https://web.archive.org/web/20150221072240/http://www.drugs.com/monograph/misoprostol.html|archive-date=21 February 2015}}</ref> It is taken ] when used to prevent gastric ulcers in people taking ]s (NSAID).<ref name=AHFS2015/> For abortions it is used by itself or in conjunction with ] or ].<ref name=":3">{{cite journal | vauthors = Zhang J, Zhou K, Shan D, Luo X | title = Medical methods for first trimester abortion | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | pages = CD002855 | date = May 2022 | issue = 5 | pmid = 35608608 | pmc = 9128719 | doi = 10.1002/14651858.CD002855.pub5 }}</ref> By itself, effectiveness for abortion is between 66% and 90%.<ref>{{cite journal | vauthors = Bryant AG, Regan E, Stuart G | s2cid = 28486936 | title = An overview of medical abortion for clinical practice | journal = Obstetrical & Gynecological Survey | volume = 69 | issue = 1 | pages = 39–45 | date = January 2014 | pmid = 25102250 | doi = 10.1097/OGX.0000000000000017 }}</ref><ref>{{cite journal | vauthors = Raymond EG, Harrison MS, Weaver MA | title = Efficacy of Misoprostol Alone for First-Trimester Medical Abortion: A Systematic Review | journal = Obstetrics and Gynecology | volume = 133 | issue = 1 | pages = 137–147 | date = January 2019 | pmid = 30531568 | pmc = 6309472 | doi = 10.1097/AOG.0000000000003017 }}</ref> For labor induction or abortion, it is taken by mouth, dissolved in the mouth, or ].<ref name=":3" /><ref>{{cite journal | vauthors = Marret H, Simon E, Beucher G, Dreyfus M, Gaudineau A, Vayssière C, Lesavre M, Pluchon M, Winer N, Fernandez H, Aubert J, Bejan-Angoulvant T, Jonville-Bera AP, Clouqueur E, Houfflin-Debarge V, Garrigue A, Pierre F | display-authors = 6 | title = Overview and expert assessment of off-label use of misoprostol in obstetrics and gynaecology: review and report by the Collège national des gynécologues obstétriciens français | journal = European Journal of Obstetrics, Gynecology, and Reproductive Biology | volume = 187 | pages = 80–4 | date = April 2015 | pmid = 25701235 | doi = 10.1016/j.ejogrb.2015.01.018 }}</ref><ref>{{cite journal |vauthors=Prager S |title=Early Pregnancy Loss |url=https://static1.squarespace.com/static/5d3a2e1399c0960001b14452/t/5dc2031df1ffb26c011ff481/1572995870418/ACOG+EPL+Bulletin_update.pdf |journal=ACOG Practice Bulletin |issue=200 |publisher=ACOG |access-date=2 June 2021 |archive-date=2 June 2021 |archive-url=https://web.archive.org/web/20210602215845/https://static1.squarespace.com/static/5d3a2e1399c0960001b14452/t/5dc2031df1ffb26c011ff481/1572995870418/ACOG+EPL+Bulletin_update.pdf |url-status=live }}</ref><ref name="ACOG Practice Bulletin No. 200: Ear" /><ref name="Early Pregnancy Loss">{{cite web | title=Early Pregnancy Loss | website=ACOG | date=20 January 2015 | url=https://www.acog.org/en/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss | access-date=25 June 2023 | archive-date=19 January 2023 | archive-url=https://web.archive.org/web/20230119024855/https://www.acog.org/en/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss | url-status=live }}</ref> For postpartum bleeding it may also be ].<ref>{{cite journal | vauthors = Blum J, Alfirevic Z, Walraven G, Weeks A, Winikoff B | title = Treatment of postpartum hemorrhage with misoprostol | journal = International Journal of Gynaecology and Obstetrics | volume = 99 | issue = Suppl 2 | pages = S202-5 | date = December 2007 | pmid = 17961565 | doi = 10.1016/j.ijgo.2007.09.013 | s2cid = 10997666 }}</ref>


<!-- Side effects and mechanism-->
Pharmacologically, misoprostol is a synthetic ] (PGE<sub>1</sub>) analogue.
Common side effects include ] and abdominal pain.<ref name=AHFS2015/> It is in ] X, meaning that it is known to result in negative outcomes for the fetus if taken during ].<ref name=AHFS2015/> In rare cases, ] may occur.<ref name=AHFS2015/> It is a ]—specifically, a synthetic ] (PGE<sub>1</sub>).<ref name=AHFS2015/>


<!-- Society and economics -->
==Ulcer prevention==
Misoprostol was developed in 1973.<ref>{{cite book|vauthors=Paul M|title=Management of Unintended and Abnormal Pregnancy: Comprehensive Abortion Care|date=2011|publisher=John Wiley & Sons|isbn=9781444358476|chapter-url=https://books.google.com/books?id=iK7xrRr2p9sC&pg=RA1-PT161|chapter=Misoprostol|access-date=18 August 2020|archive-date=29 June 2022|archive-url=https://web.archive.org/web/20220629032410/https://books.google.com/books?id=iK7xrRr2p9sC&pg=RA1-PT161|url-status=live}}</ref> It is on the ].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> It is available as a ].<ref name=AHFS2015/>
Misoprostol is approved for use in the prevention of ] induced gastric ulcers. It acts upon gastric ]s, inhibiting the secretion of ] via ] mediated inhibition of ], which leads to decreased intracellular ] levels and decreased ] activity at the ] surface of the parietal cell. Because other classes of drugs, especially ] and ], are more effective for the treatment of acute peptic ulcers, Misoprostol is only indicated for use by people who are both taking NSAIDs and are at high risk for NSAID induced ulcers, including the elderly and people with ulcer complications. Misoprostol is sometimes coprescribed with NSAIDs to prevent their common adverse effect of ]ation (e.g. with ] in ]).


==Medical uses==
Misoprostol has other protective actions, but is only clinically effective at doses high enough to reduce gastric acid secretion. For instance, at lower doses misoprostol may stimulate increased secretion of the protective ] that lines the ] and increase mucosal blood flow, thereby increasing mucosal integrity. However, these effects are not pronounced enough to warrant prescription of misoprostol at doses lower than those needed to achieve gastric acid suppression.


===Ulcer prevention===
However, even in the treatment of NSAIDs induced ulcers, ] proved to be at least as effective as misoprostol, but significantly better tolerated, and therefore misoprostol should not be considered a first choice treatment. Misoprostol induced diarrhea and the need of multiple daily doses (typically four) are the main issues impairing adherence to therapy.
Misoprostol is used for the prevention of ]-induced gastric ulcers. It acts upon gastric ]s, inhibiting the secretion of ] by ]-mediated inhibition of ], which leads to decreased intracellular ] levels and decreased ] activity at the ] surface of the parietal cell. Misoprostol is sometimes coprescribed with NSAIDs to prevent their common adverse effect of ]ation (e.g., with ] in '']'').{{cn|date=May 2022}}


However, even in the treatment of NSAID-induced ulcers, ] proved to be at least as effective as misoprostol,<ref>{{cite journal | vauthors = Hawkey CJ, Karrasch JA, Szczepañski L, Walker DG, Barkun A, Swannell AJ, Yeomans ND | display-authors = 6 | title = Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group | journal = The New England Journal of Medicine | volume = 338 | issue = 11 | pages = 727–34 | date = March 1998 | pmid = 9494149 | doi = 10.1056/NEJM199803123381105 | hdl = 2445/178575 | hdl-access = free }}</ref> but was significantly better tolerated, so misoprostol should not be considered a first-line treatment. Misoprostol-induced diarrhea and the need for multiple daily doses (typically four) are the main issues impairing compliance with therapy.{{medcn|date=June 2023}}
==Labor induction==
Misoprostol is commonly used for ]. It causes uterine contractions and the ripening (] or thinning) of the ].<ref>{{cite journal |author=Goldberg AB, Greenberg MB, Darney PD |title=Misoprostol and pregnancy |journal=N. Engl. J. Med. |volume=344 |issue=1 |pages=38–47 |year=2001 |month=January |pmid=11136959 |doi=10.1056/NEJM200101043440107}}</ref> Misoprostol is more effective in starting labor than other drugs used for labor induction.<ref name="wagner">{{cite book |author=Wagner, Marsden |title=Born in the USA: how a broken maternity system must be fixed to put mothers and infants first |publisher=University of California Press |location=Berkeley |year=2006 |isbn=0-520-24596-2}}</ref>{{rp|87}} It is also significantly less expensive than the other commonly used ripening agent, ] (trade names ''Cervidil'' and ''Prepidil'').<ref name="summers"/>


===Labor induction===
] (trade names ''Pitocin'' and ''Syntocinon'') has long been used as the standard agent for labor induction, but doesn't work well when the cervix is not yet ripe. In addition to being used alone to induce labor, misoprostol may be used in conjunction with oxytocin.<ref name="summers">{{cite journal |author=Summers L |title=Methods of cervical ripening and labor induction |journal=J Nurse Midwifery |volume=42 |issue=2 |pages=71–85 |year=1997 |pmid=9107114 |doi=10.1016/S0091-2182(96)00138-3}}</ref>
Misoprostol is commonly used for ]. It causes ] contractions and the ripening (] or thinning) of the ].<ref>{{cite journal | vauthors = Goldberg AB, Greenberg MB, Darney PD | title = Misoprostol and pregnancy | journal = The New England Journal of Medicine | volume = 344 | issue = 1 | pages = 38–47 | date = January 2001 | pmid = 11136959 | doi = 10.1056/NEJM200101043440107 }}</ref> It can be less expensive than the other commonly used ripening agent, ].<ref name="summers"/>


] has long been used as the standard agent for labor induction, but does not work well when the cervix is not yet ripe. Misoprostol also may be used in conjunction with oxytocin.<ref name="summers">{{cite journal | vauthors = Summers L | title = Methods of cervical ripening and labor induction | journal = Journal of Nurse-Midwifery | volume = 42 | issue = 2 | pages = 71–85 | year = 1997 | pmid = 9107114 | doi = 10.1016/S0091-2182(96)00138-3 }}</ref>
Protocols for inducing labor with misoprostol typically call for 25&nbsp;μg to be administered vaginally.<ref name="goldberg"/> In countries where the only approved use of misoprostol is ulcer prevention, misoprostol is not sold in tablets smaller than 100&nbsp;μg. When used for induction, the 100&nbsp;μg tablet is commonly split into two or four pieces.<ref name="briggs"/>


Between 2002 and 2012, a misoprostol vaginal insert was studied, and was approved in the EU.<ref>{{cite press release | title=Misodel, Ferring's Removable Misoprostol Vaginal Delivery System, Approved for Labour Induction in European Decentralised Procedure | publisher=Ferring Pharmaceuticals | via=Business Wire | date=17 October 2013 | url=https://www.businesswire.com/news/home/20131017005499/en/MISODEL%E2%84%A2-Ferring%E2%80%99s-Removable-Misoprostol-Vaginal-Delivery-System-Approved-for-Labour-Induction-in-European-Decentralised-Procedure | access-date=25 June 2023}}</ref><ref>{{cite journal | vauthors = Wing DA, Brown R, Plante LA, Miller H, Rugarn O, Powers BL | title = Misoprostol vaginal insert and time to vaginal delivery: a randomized controlled trial | journal = Obstetrics and Gynecology | volume = 122 | issue = 2 Pt 1 | pages = 201–9 | date = August 2013 | pmid = 23857539 | doi = 10.1097/AOG.0b013e31829a2dd6 | s2cid = 31090241 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Varlas VN, Bostan G, Nasui BA, Bacalbasa N, Pop AL | title = Is Misoprostol Vaginal Insert Safe for the Induction of Labor in High-Risk Pregnancy Obese Women? | journal = Healthcare | volume = 9 | issue = 4 | pages = 464 | date = April 2021 | pmid = 33919898 | pmc = 8070889 | doi = 10.3390/healthcare9040464 | doi-access = free }}</ref> It was not approved for use in the United States, and the US FDA still considers cervical ripening and labor induction to be outside of the approved uses for misoprostol.<ref>{{cite web|title=Safety Information, Cytotec (misoprostol) Tablets|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm330991.htm|publisher=U.S. ] (FDA)|access-date=16 March 2017|date=11 December 2012|archive-url=https://web.archive.org/web/20170120123024/http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm330991.htm|archive-date=20 January 2017|url-status=dead}}</ref><ref>{{cite web|title=Misoprostol (marketed as Cytotec) Information|url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/misoprostol-marketed-cytotec-information|publisher=U.S. ] (FDA)|access-date=17 August 2020|date=10 July 2015|archive-url=https://web.archive.org/web/20200527035726/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/misoprostol-marketed-cytotec-information|archive-date=27 May 2020|url-status=live}}</ref>
===Controversy===


===Myomectomy===
When Cytotec first came on the market, the label listed a contraindication that it not be used on pregnant women. In August 2000, due to increase of "off label" usage, ] (the manufacturer of Cytotec) distributed a letter warning against the use of misoprostol in pregnant women. In addition to citing the ] nature of the drug, the letter cited reports of ] and death associated with using misoprostol to induce labor. All cervical ripening and induction agents can cause ], which can negatively affect the blood supply to the fetus and increases the risk of complications such as uterine rupture.<ref name="briggs">{{cite journal |author=Briggs GG, Wan SR |title=Drug therapy during labor and delivery, part 2 |journal=Am J Health Syst Pharm |volume=63 |issue=12 |pages=1131–9 |year=2006 |month=June |pmid=16754739 |doi=10.2146/ajhp050265.p2 |url=http://www.medscape.com/viewarticle/535774 |accessdate=2009-08-03}}</ref> Concern has been raised that uterine hyperstimulation that occurs during a misoprostol induced labor is more difficult to treat than hyperstimulation during labors induced by other drugs.<ref>Wagner (2006), which cites:
When administered prior to ] in women with uterine fibroids, misoprostol reduces operative blood loss and requirement of blood transfusion.<ref>{{cite journal | vauthors = Wali S, Balfoussia D, Touqmatchi D, Quinn S | title = Misoprostol for open myomectomy: a systematic review and meta-analysis of randomised control trials | journal = BJOG | volume = 128 | issue = 3 | pages = 476–483 | date = February 2021 | pmid = 32613769 | doi = 10.1111/1471-0528.16389 | s2cid = 220307235 }}</ref>
:{{cite journal |author=Wing DA, Paul RH |title=A comparison of differing dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and labor induction |journal=Am. J. Obstet. Gynecol. |volume=175 |issue=1 |pages=158–64 |year=1996 |month=July |pmid=8694043 |doi=10.1016/S0002-9378(96)70267-3}}
:{{cite journal |author=Wing DA, Rahall A, Jones MM, Goodwin TM, Paul RH |title=Misoprostol: an effective agent for cervical ripening and labor induction |journal=Am. J. Obstet. Gynecol. |volume=172 |issue=6 |pages=1811–6 |year=1995 |month=June |pmid=7778637 |doi=10.1016/0002-9378(95)91416-1}}</ref> Other rare complications include ]; a 2006 study showed that the use of drugs to induce labor nearly doubled the risk.<ref name="kramer 2006">{{cite journal |author=Kramer, M.S. |title=Amniotic-fluid embolism and medical induction of labour: a retrospective, population-based cohort study |journal=The Lancet |volume=368 |issue=9545 |pages=1444–1448 |year=2006 |doi=10.1016/S0140-6736(06)69607-4|url=http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69607-4/abstract |last2=Rouleau |first2=Jocelyn |last3=Baskett |first3=Thomas F |last4=Joseph |first4=KS}}</ref> Because the complications are rare, it is difficult to determine if misoprostol causes a higher risk than do other cervical ripening agents. One estimate is that it would require approximately 61,000 patients enrolled in randomized controlled trials to detect a clinically significant difference in serious fetal complications and approximately 155,000 patients to detect a clinically significant difference in serious maternal complications.<ref>Goldberg (2003), which cites:
:{{cite journal |author=Weeks A, Alfirevic Z |title=Oral misoprostol administration for labor induction |journal=Clin Obstet Gynecol |volume=49 |issue=3 |pages=658–71 |year=2006 |month=September |pmid=16885670 |doi=10.1097/00003081-200609000-00023}}</ref>


===Abortion===
This letter generated much controversy over the use of misoprostol in labor inductions.<ref name="goldberg">{{cite journal |author=Goldberg AB, Wing DA |title=Induction of labor: the misoprostol controversy |journal=J Midwifery Womens Health |volume=48 |issue=4 |pages=244–8 |year=2003 |pmid=12867908 |doi= 10.1016/S1526-9523(03)00087-4|url=http://www.medscape.com/viewarticle/458959 |accessdate=2009-08-03}}</ref> The ] holds that substantial evidence supports the use of misoprostol for induction of labor, a position it reaffirmed in 2000 in response to the Searle letter.<ref>Goldberg (2003), which cites:
Misoprostol is used either alone or in conjunction with another medication (] or ]) for ]s as an alternative to ].<ref>{{Cite web|title = Medical methods for first trimester abortion|url = http://apps.who.int/rhl/fertility/abortion/dgguide/en/|website = ] (WHO) |access-date = 4 February 2016|url-status = dead|archive-url = https://web.archive.org/web/20160214074838/http://apps.who.int/rhl/fertility/abortion/dgguide/en/|archive-date = 14 February 2016}}</ref> Medical abortion has the advantage of being less invasive, and more autonomous, self-directed, and discreet. It is preferred by some women because it feels more natural, as the drugs induce a miscarriage.<ref>{{cite journal | vauthors = Harvey SM, Beckman LJ, Castle MA, Coeytaux F | s2cid = 30491792 | title = Knowledge and perceptions of medical abortion among potential users | journal = Family Planning Perspectives | volume = 27 | issue = 5 | pages = 203–7 | date = 1 October 1995 | pmid = 9104607 | doi = 10.2307/2136276 | jstor = 2136276 }}</ref> It is also more easily accessible in places where abortion is illegal.<ref>{{Cite news|title = The Dawn of the Post-Clinic Abortion|url = https://www.nytimes.com/2014/08/31/magazine/the-dawn-of-the-post-clinic-abortion.html|newspaper = The New York Times|date = 28 August 2014|access-date = 4 February 2016|issn = 0362-4331| vauthors = Bazelon E |url-status = live|archive-url = https://web.archive.org/web/20160428103240/http://www.nytimes.com/2014/08/31/magazine/the-dawn-of-the-post-clinic-abortion.html|archive-date = 28 April 2016}}</ref> The ] (WHO) provides clear guidelines on the use, benefits and risks of misoprostol for abortions.<ref>{{cite web|title= Medical methods for first trimester abortion|publisher= The WHO Medical Reproductive Library|url= http://apps.who.int/rhl/fertility/abortion/dgguide/en/|access-date= 22 June 2014|url-status= dead|archive-url= https://web.archive.org/web/20140802174632/http://apps.who.int/rhl/fertility/abortion/dgguide/en/|archive-date= 2 August 2014}}</ref>
:{{cite journal |author=American College of Obstetricians and Gynecologists |authorlink=American College of Obstetricians and Gynecologists |title=Induction of labor with misoprostol |journal=ACOG committee opinion no. 228 |location=Washington, DC |year=1999 |month=November}}
:{{cite journal |author=American College of Obstetricians and Gynecologists |authorlink=American College of Obstetricians and Gynecologists |title=Response to Searle's drug warning on misoprostol |journal=ACOG committee opinion no. 248 |location=Washington, DC |year=1999 |month=November}}</ref> Misoprostol is also on the WHO essential drug list for labor induction.<ref>{{cite web|title=WHO Essential drug list 2005 section 22.1 website|author=WHO|url=http://whqlibdoc.who.int/hq/2005/a87017_eng.pdf|format=PDF|accessdate=2006-12-06}}</ref>


Misoprostol is most effective when it is used in combination with methotrexate or mifepristone (RU-486).<ref name=":0">{{Cite book|title=Safe abortion : technical and policy guidance for health systems | publisher = World Health Organization |isbn=9789241548434|edition=Second|location=Geneva|oclc=812323067|year = 2012}}</ref> Mifepristone blocks signaling by ], causing the uterine lining to degrade, the blood vessels of the ] and ] to dilate and causing uterine contraction, similar to a ], which causes the embryo to detach from the uterine walls.<ref name=AHFS2023>{{cite web|title=Mifepristone|url=https://www.drugs.com/monograph/mifepristone.html|publisher=The American Society of Health System Pharmacists|access-date=25 February 2023|date=18 January 2023|url-status=live|archive-date=22 December 2015|archive-url=https://web.archive.org/web/20151222083002/http://www.drugs.com/monograph/mifepristone.html}}</ref> Misoprostol then dilates the cervix and induces muscle contractions which clear the uterus.{{citation needed|date=March 2021}} Misoprostol alone is less effective (typically 88% up to eight-weeks gestation). It is not inherently unsafe if medically supervised, but 1% of women will have heavy bleeding requiring medical attention, some women may have ], and the 12% of pregnancies that continue after misoprostol failure are more likely to have birth defects and are usually followed up with a more effective method of abortion.<ref name="Gunter"> {{webarchive|url=https://web.archive.org/web/20130730235702/http://drjengunter.wordpress.com/2013/07/27/what-is-the-mexican-abortion-pill-and-how-safe-is-it/ |date=30 July 2013 }} Jen Gunter, 27 July 2013</ref>
==Induced abortion==
===Earlier pregnancy===
Misoprostol is one of the drugs used for ]s in lieu of surgical evacuation. The advantages of medical abortion over ] include reduced invasiveness of the procedure, lack of risks from ] (which is sometimes used for surgical abortions), and lack of risk of secondary ] due to scarring and ] (]).{{Citation needed|date=March 2008}} Furthermore, it is less complicated to administer and less expensive.


Most large studies recommend a protocol for the use of misoprostol in combination with mifepristone.<ref>{{cite web|title=Annotated Bibliography on Misoprostol Alone for Early Abortion|publisher=Gynuity Health Projects|url=https://gynuity.org/assets/resources/biblioref_misoearlyab.pdf |access-date=22 August 2006|url-status=live |archive-url=https://web.archive.org/web/20070929071156/http://www.rhtp.org/news/publications/documents/Miso%20for%20Pregnancy%20Termination.Bibliography.pdf|archive-date=29 September 2007}}</ref><ref>{{cite web | title=Annotated Bibliography - Misoprostol for Early Abortion | website=Gynuity Health Projects | date=1 September 2004 | url=https://gynuity.org/resources/annotated-bibliography-misoprostol-for-early-abortion | access-date=25 June 2023 | archive-date=18 May 2022 | archive-url=https://web.archive.org/web/20220518184738/https://gynuity.org/resources/annotated-bibliography-misoprostol-for-early-abortion | url-status=live }}</ref> Together they are effective in around 95% for early pregnancies.<ref>{{cite book|title=Providing medical abortion in low-resource settings|date=2009|publisher=Gynuity Health Projects|page=4|edition=2|url=https://gynuity.org/assets/resources/clinguide_maguide2nd_edition_en.pdf |url-status=live |archive-url=https://web.archive.org/web/20160222095552/http://gynuity.org/downloads/clinguide_maguide2nd_edition_en.pdf|archive-date=22 February 2016|access-date=31 August 2015}}</ref> Misoprostol alone may be more effective in earlier gestation.<ref>{{cite web|title=Instructions for Use: Abortion Induction with Misoprostol in Pregnancies up to 9 Weeks LMP|publisher=Gynuity Health Projects |year=2003|url=https://gynuity.org/assets/resources/clinguide_ifu_abortion_en.pdf |access-date=24 August 2006|url-status=live |archive-url=https://web.archive.org/web/20070929071204/http://www.rhtp.org/news/publications/documents/Miso%20for%20Pregnancy%20Termination.IFU.English.pdf#search=%22%20site%3Awww.rhtp.org%20misoprostol%20abortion%20success%20rate%22|archive-date=29 September 2007}}</ref>
In many countries{{Which?|date=February 2009}} it is used in conjunction with ] (RU-486). After mifepristone is taken orally, misoprostol is taken 24&ndash;72 hours later, causing the expulsion of the embryo and associated matter in approximately 92% of the cases. No large studies have established a protocol for the use of misoprostol alone,<ref>{{cite web|title=Annotated Bibliography on Misoprostol Alone for Early Abortion|publisher=Gynuity Health Projects|url=http://www.rhtp.org/news/publications/documents/Miso%20for%20Pregnancy%20Termination.Bibliography.pdf|format=PDF|accessdate=2006-08-22}}</ref> and the range of efficacy is 65%&ndash;93% depending on sample size, gestational age, and other test variables;<ref>{{cite web|title=Medication Abortion: Misoprostol Alone|publisher=Ibis|accessdate=2006-09-08|url=http://www.medicationabortion.com/misoprostol/index.html}}</ref> Misoprostol alone may be more effective in earlier gestation.<ref>{{cite web|title=Instructions for Use: Abortion Induction with Misoprostol in Pregnancies up to 9 Weeks LMP|publisher=Gynuity Health Projects|format=PDF|year=2003|url=http://www.rhtp.org/news/publications/documents/Miso%20for%20Pregnancy%20Termination.IFU.English.pdf#search=%22%20site%3Awww.rhtp.org%20misoprostol%20abortion%20success%20rate%22|accessdate=2006-08-24}}</ref> The side effects associated with the misoprostol only regimen are generally much more severe than those associated with the combined regimens.{{Citation needed|date=August 2010}} Misoprostol is used for ]s in Brazil, where ] 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.<ref>{{cite journal|author=Corta, SH et al.|title=Misoprostol and illegal abortion in Rio de Janeiro, Brazil|journal=Lancet|year=1993|volume=15|issue=341|pmid=8098402|pages=1258–61|doi=10.1016/0140-6736(93)91156-G}}</ref><ref>{{cite journal|author=Coelho, HL et al.|title=Misoprostol: the experience of women in Fortaleza, Brazil|journal=Contraception|year=1994|volume=49|issue=2|pages=101–10|pmid=8143449|doi=10.1016/0010-7824(94)90084-1}}</ref><ref>{{cite journal|author=Barbosa, RM|title=The Brazilian Experience with Cytotec|journal=Stud Fam Plann|year=1993|volume=24|issue=4|pages=236–40|pmid=8212093|doi=10.2307/2939191|last2=Arilha|first2=M|jstor=2939191}}</ref><ref>{{cite journal|author=Rocha, J et al.|title=Brazil investigates drug's possible link with birth defects|journal=BMJ|year=1994|volume=309|issue=6957|pmid=7950553|pages=757–8}}</ref><ref>{{cite journal|author=Gonzalez, CH et al.|title=Limb deficiency with or without Mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy|journal=Am J Med Genet|year=1993|volume=47|issue=1|pages=59–64|pmid=8368254|doi=10.1002/ajmg.1320470113}}</ref> Poor immigrant populations in ] 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).<ref>]: "", '']'', October 2, 2005</ref>


Misoprostol can also be used to ] in preparation for a surgical abortion, particularly in the second trimester (either alone or in combination with ]). Vaginal misoprostol can also be used to facilitate ] insertion after previous insertion failure.<ref>{{cite journal | vauthors = Rasheedy R, Tamara TF, Allam IS, Abbas AM, Essam El-Din Abd El Salam N, Ferhad Ahmed A | title = Vaginal misoprostol before copper IUD insertion after previous insertion failure: a double-blind, placebo-controlled, parallel-group, randomised clinical trial | journal = The European Journal of Contraception & Reproductive Health Care | volume = 24 | issue = 3 | pages = 222–226 | date = June 2019 | pmid = 31112079 | doi = 10.1080/13625187.2019.1610871 | s2cid = 160014019 }}{{Retracted|doi=10.1080/13625187.2023.2171653|pmid=36744398}}</ref>
===Later pregnancy===
Misoprostol can also be used to dilate the cervix in preparation for a surgical abortion, particularly in the second trimester (either alone or in combination with ] stents).


Misoprostol by mouth is the least effective treatment for producing complete abortion in a period of 24 hours due to the liver's ] which reduces the ] of the misoprostol. Vaginal and sublingual routes result in greater efficacy and extended duration of action because these routes of administration allow the drug to be directly absorbed into circulation by bypassing the liver first-pass effect.<ref name=":1" /><ref name="ACOG Practice Bulletin No. 200: Ear">{{cite journal | title = ACOG Practice Bulletin No. 200: Early Pregnancy Loss | journal = Obstetrics and Gynecology | volume = 132 | issue = 5 | pages = e197–e207 | date = November 2018 | pmid = 30157093 | doi = 10.1097/AOG.0000000000002899 | author1 = American College of Obstetricians Gynecologists' Committee on Practice Bulletins—Gynecology | s2cid = 13149908 }}</ref><ref name="Early Pregnancy Loss" />
==Missed miscarriage==
Misoprostol is sometimes used to treat early fetal death in the absence of spontaneous ], but further research is needed to establish a safe, effective protocol.<ref>{{cite journal|author=Neilson JP et al.|title=Medical treatment for early fetal death (less than 24 weeks)|journal=Cochrane Database Syst Rev|year=2006|volume=19|issue=3|pmid=16855990|doi=10.1002/14651858.CD002253.pub3|pages=CD002253|editor1-last=Neilson|editor1-first=James P}}</ref>


] or Hb tests and Rh testing are recommended before use for abortion confirmation of pregnancy.<ref name=":2">{{cite journal | title = Practice bulletin no. 143: medical management of first-trimester abortion | journal = Obstetrics and Gynecology | volume = 123 | issue = 3 | pages = 676–92 | date = March 2014 | pmid = 24553166 | doi = 10.1097/01.AOG.0000444454.67279.7d | author1 = American College of Obstetricians Gynecologists | s2cid = 23951273 | doi-access = }}</ref> Following use, it is recommended that people attend a follow-up visit 2 weeks after treatment. If used for treatment of complete abortion, a pregnancy test, physical examination of the uterus, and ultrasound should be performed to ensure success of treatment. Surgical management is possible in the case of failed treatment.<ref name=":1" />
==Post-partum hemorrhage==
Misoprostol is also used to prevent and treat ], but it has more side effects and is less effective than ] for this purpose.<ref>{{cite web|author=J Villar MD et al.|title=Systematic Review of Randomized Controlled Trials of Misoprostol to Prevent Postpartum Hemorrhage|publisher=Obstetrics & Gynecology|year=2002|accessdate=2006-09-21|url=http://www.greenjournal.org/cgi/content/abstract/100/6/1301}}</ref> However, it is inexpensive and thermostable (thus does not require refrigeration like oxytocin) making it a cost effective and valuable drug to use in the developing world.<ref>Bradley SEK, Prata N, Young-Lin N, Bishai DM (2007). "Cost-effectiveness of misoprostol to control postpartum hemorrhage in low-resource settings." ''International Journal of Gynecology and Obstetrics'', '''97''': 52–56.</ref>


===Early pregnancy loss===
==Other gynecological uses==
Misoprostol may be used to complete a ] or ] when the body does not expel the embryo or fetus on its own. Compared to no medication or placebo, it could decrease the time to complete expulsion.<ref>{{cite journal | vauthors = Lemmers M, Verschoor MA, Kim BV, Hickey M, Vazquez JC, Mol BW, Neilson JP | display-authors = 6 | title = Medical treatment for early fetal death (less than 24 weeks) | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD002253 | date = June 2019 | issue = 6 | pmid = 31206170 | pmc = 6574399 | doi = 10.1002/14651858.CD002253.pub4 }}</ref> Use of a single dose of misoprostol vaginally or buccally is preferred, with additional doses as needed. It also can be used in combination with mifepristone, with a similar regimen to medical abortion.<ref name="ACOG Practice Bulletin No. 200: Ear"/><ref name="Early Pregnancy Loss" />
Although the practice remains uncommon, some gynecologists are now using low doses of misoprostol to soften the cervix prior to the insertion of ]s (especially in ] women where insertion may be challenging).


Misoprostol is regularly used in some Canadian hospitals for labour induction for fetal deaths early in pregnancy, and for termination of pregnancy for fetal anomalies. A low dose is used initially, then doubled for the remaining doses until delivery. In the case of a previous Caesarian section, however, lower doses are used.
==Erectile dysfunction==

A 1998 study found misoprostol to be helpful as a supplement to a vacuum pump (VED) in the treatment of ], but not effective by itself.<ref>{{cite journal | author=Ekmekçioğlu, Demirci, Yilmaz & Tatli|title=Intraurethral misoprostol: a different agent in the treatment of erectile dysfunction|journal=Sexual Dysfunction|year=1998|volume=1|pages=161 |doi=10.1046/j.1460-2679.1998.00030.x | url=http://www.blackwell-synergy.com/doi/full/10.1046/j.1460-2679.1998.00030.x | issue=3}}</ref> 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".
===Postpartum bleeding===
Misoprostol is also used to prevent and treat ]. Orally administered misoprostol was marginally less effective than ].<ref>{{cite journal | vauthors = Villar J, Gülmezoglu AM, Hofmeyr GJ, Forna F | s2cid = 24561459 | title = Systematic review of randomized controlled trials of misoprostol to prevent postpartum hemorrhage | journal = Obstetrics and Gynecology | volume = 100 | issue = 6 | pages = 1301–12 | date = December 2002 | pmid = 12468178 | doi = 10.1016/S0029-7844(02)02371-2 }}</ref> The use of rectally administered misoprostol is optimal in cases of bleeding; it was shown to be associated with lower rates of side effects compared to other routes. Rectally administered misoprostol was reported in a variety of case reports and randomised controlled trials.<ref>{{cite journal | vauthors = O'Brien P, El-Refaey H, Gordon A, Geary M, Rodeck CH | title = Rectally administered misoprostol for the treatment of postpartum hemorrhage unresponsive to oxytocin and ergometrine: a descriptive study | journal = Obstetrics and Gynecology | volume = 92 | issue = 2 | pages = 212–4 | date = August 1998 | pmid = 9699753 | doi = 10.1016/S0029-7844(98)00161-6 }}</ref><ref>{{cite journal | vauthors = Lokugamage AU, Sullivan KR, Niculescu I, Tigere P, Onyangunga F, El Refaey H, Moodley J, Rodeck CH | display-authors = 6 | title = A randomized study comparing rectally administered misoprostol versus Syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 80 | issue = 9 | pages = 835–9 | date = September 2001 | pmid = 11531635 | doi = 10.1034/j.1600-0412.2001.080009835.x | s2cid = 23335277 | doi-access = free }}</ref> However, it is inexpensive and thermostable (thus does not require refrigeration like oxytocin), making it a cost-effective and valuable drug to use in the developing world.<ref>{{cite journal | vauthors = Bradley SE, Prata N, Young-Lin N, Bishai DM | title = Cost-effectiveness of misoprostol to control postpartum hemorrhage in low-resource settings | journal = International Journal of Gynaecology and Obstetrics | volume = 97 | issue = 1 | pages = 52–6 | date = April 2007 | pmid = 17316646 | doi = 10.1016/j.ijgo.2006.12.005 | s2cid = 23593148 }}</ref> A randomised control trial of misoprostol use found a 38% reduction in maternal deaths due to ''post partum'' haemorrhage in resource-poor communities.<ref>{{cite journal | vauthors = Derman RJ, Kodkany BS, Goudar SS, Geller SE, Naik VA, Bellad MB, Patted SS, Patel A, Edlavitch SA, Hartwell T, Chakraborty H, Moss N | s2cid = 22275092 | display-authors = 6 | title = Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial | journal = Lancet | volume = 368 | issue = 9543 | pages = 1248–53 | date = October 2006 | pmid = 17027730 | doi = 10.1016/S0140-6736(06)69522-6 }}</ref> Misoprostol is recommended due to its cost, effectiveness, stability, and low rate of side effects.<ref>{{cite book | vauthors = Sanghvi H, Zulkarnain M, Chanpong G | veditors = Blouse A, Lewison D |year=2009 |title=Prevention of Postpartum Hemorrhage at Home Birth: A Program Implementation Guide |publisher=] |url=http://pdf.usaid.gov/pdf_docs/PNADX368.pdf |url-status=live |archive-url=https://web.archive.org/web/20131206122217/http://pdf.usaid.gov/pdf_docs/PNADX368.pdf |archive-date=6 December 2013 }}{{page needed|date=September 2012}}</ref> Oxytocin must also be given by injection, while misprostol can be given orally or rectally for this use, making it much more useful in areas where nurses and physicians are less available.<ref>{{cite journal | vauthors = Prata N, Passano P, Bell S, Rowen T, Potts M | title = New hope: community-based misoprostol use to prevent postpartum haemorrhage | journal = Health Policy and Planning | volume = 28 | issue = 4 | pages = 339–46 | date = July 2013 | pmid = 22879523 | doi = 10.1093/heapol/czs068 | doi-access = free }}</ref>

===Insertion of intrauterine contraceptive device===
In women with prior caesarean section or prior failure of insertion of an intrauterine contraceptive device, pre-procedure administration of misoprostol reduces the rate of failure of insertion of intrauterine contraceptive device. However, due to a higher rate of adverse effects, routine use of misoprostol for this purpose in other women is not supported by the data.<ref>{{cite journal |vauthors=Tassi A, Parisi N, Londero AP |title=Misoprostol administration prior to intrauterine contraceptive device insertion: a systematic review and meta-analysis of randomised controlled trials |journal=Eur J Contracept Reprod Health Care |volume=25 |issue=1 |pages=76–86 |date=February 2020 |pmid=31914331 |doi=10.1080/13625187.2019.1706079 |s2cid=210120219 |url=https://figshare.com/articles/dataset/Misoprostol_administration_prior_to_intrauterine_contraceptive_device_insertion_a_systematic_review_and_meta-analysis_of_randomised_controlled_trials/11555661 |access-date=21 June 2022 |archive-date=29 June 2022 |archive-url=https://web.archive.org/web/20220629032412/https://figshare.com/articles/dataset/Misoprostol_administration_prior_to_intrauterine_contraceptive_device_insertion_a_systematic_review_and_meta-analysis_of_randomised_controlled_trials/11555661 |url-status=live }}</ref>

===Other===
For ] in advance of endometrial biopsy to reduce the need for use of a tenaculum or cervical dilator.{{cn|date=May 2022}}

There is limited evidence supporting the use of misoprostol for the treatment of ] in patients with ].<ref>{{cite journal | vauthors = ((DMKG study group))| title = Misoprostol in the treatment of trigeminal neuralgia associated with multiple sclerosis | journal = Journal of Neurology | volume = 250 | issue = 5 | pages = 542–545 | date = May 2003 | pmid = 12736732 | doi = 10.1007/s00415-003-1032-1 | s2cid = 36493785 }}</ref><ref>{{cite journal | vauthors = Di Stefano G, Truini A, Cruccu G | title = Current and Innovative Pharmacological Options to Treat Typical and Atypical Trigeminal Neuralgia | journal = Drugs | volume = 78 | issue = 14 | pages = 1433–1442 | date = September 2018 | pmid = 30178160 | pmc = 6182468 | doi = 10.1007/s40265-018-0964-9 }}</ref>

==Adverse effects==
The most commonly reported ] of taking misoprostol by mouth for the prevention of stomach ulcers is ]. In clinical trials, an average 13% of people reported diarrhea, which was dose-related and usually developed early in the course of therapy (after 13 days) and was usually self-limiting (often resolving within 8 days), but sometimes (in 2% of people) required discontinuation of misoprostol.<ref name="Cytotec USPI">{{cite web | title=Cytotec- misoprostol tablet | website=DailyMed | date=9 July 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ab12da7-5731-4e06-bf1c-bc3f2e711f12 | access-date=25 June 2023 | archive-date=18 April 2023 | archive-url=https://web.archive.org/web/20230418121539/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ab12da7-5731-4e06-bf1c-bc3f2e711f12 | url-status=live }}</ref>

The next most commonly reported adverse effects of taking misoprostol by mouth for the prevention of gastric ulcers are: ], ], ], ], ], ], and ], but none of these adverse effects occurred more often than when taking ]s.<ref name="Cytotec USPI"/>

There are increased side effects with sublingual or oral misoprostol, compared to a low dose (400&nbsp;μg) vaginal misoprostol. However, low dose vaginal misoprostol was linked with low complete abortion rate.<ref name=":1">{{cite journal | vauthors = Wu HL, Marwah S, Wang P, Wang QM, Chen XW | title = Misoprostol for medical treatment of missed abortion: a systematic review and network meta-analysis | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 1664 | date = May 2017 | pmid = 28490770 | pmc = 5431938 | doi = 10.1038/s41598-017-01892-0 | bibcode = 2017NatSR...7.1664W }} ] Material was copied from this source, which is available under a {{Webarchive|url=https://web.archive.org/web/20171016050101/https://creativecommons.org/licenses/by/4.0/ |date=16 October 2017 }}.</ref> The study concluded that sublingually administered misoprostol dosed at 600&nbsp;μg or 400&nbsp;μg had greater instances of fever and diarrhea due to its quicker onset of action, higher peak concentration and bioavailability in comparison to vaginal or oral misoprostol.<ref name=":1" />

For the indication of medical abortion, bleeding and cramping is commonly experienced after administration of misoprostol. Bleeding and cramping is likely to be greater than that experienced with menses, however, emergency care is advised if bleeding is excessive.<ref name=":2" />

Misoprostol should not be taken by pregnant women with wanted pregnancies to reduce the risk of NSAID-induced gastric ulcers because it increases uterine tone and contractions in pregnancy, which may cause partial or complete abortions, and because its use in pregnancy has been associated with birth defects.<ref name="Cytotec USPI"/><ref name="Cytotec UK SPC">{{cite web | title=Cytotec 200mcg Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=26 April 2021 | url=https://www.medicines.org.uk/emc/product/1642/smpc | access-date=25 June 2023 | archive-date=1 July 2022 | archive-url=https://web.archive.org/web/20220701225414/https://www.medicines.org.uk/emc/product/1642/smpc | url-status=live }}</ref>

All cervical ripening and induction agents can cause ], which can negatively affect the blood supply to the fetus and increases the risk of complications such as uterine rupture.<ref name="briggs">{{cite journal | vauthors = Briggs GG, Wan SR | title = Drug therapy during labor and delivery, part 2 | journal = American Journal of Health-System Pharmacy | volume = 63 | issue = 12 | pages = 1131–9 | date = June 2006 | pmid = 16754739 | doi = 10.2146/ajhp050265.p2 }}</ref> Concern has been raised that uterine hyperstimulation that occurs during a misoprostol-induced labor is more difficult to treat than hyperstimulation during labors induced by other drugs.<ref>{{cite book | vauthors = Wagner M |title=Born in the USA: how a broken maternity system must be fixed to put mothers and infants first |publisher=University of California Press |location=Berkeley |year=2006 |isbn=0-520-24596-2}}, which cites:
: {{cite journal | vauthors = Wing DA, Paul RH | title = A comparison of differing dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and labor induction | journal = American Journal of Obstetrics and Gynecology | volume = 175 | issue = 1 | pages = 158–64 | date = July 1996 | pmid = 8694043 | doi = 10.1016/s0002-9378(96)70267-3 }}
:{{cite journal | vauthors = Wing DA, Rahall A, Jones MM, Goodwin TM, Paul RH | title = Misoprostol: an effective agent for cervical ripening and labor induction | journal = American Journal of Obstetrics and Gynecology | volume = 172 | issue = 6 | pages = 1811–6 | date = June 1995 | pmid = 7778637 | doi = 10.1016/0002-9378(95)91416-1 }}</ref> Because the complications are rare, it is difficult to determine if misoprostol causes a higher risk than do other cervical ripening agents. One estimate is that it would require around 61,000 people enrolled in randomized controlled trials to detect a difference in serious fetal complications and about 155,000 people to detect a difference in serious maternal complications.<ref>{{harvnb|Goldberg|Wing|2003}}, which cites:
:{{cite journal | vauthors = Weeks A, Alfirevic Z | s2cid = 13063131 | title = Oral misoprostol administration for labor induction | journal = Clinical Obstetrics and Gynecology | volume = 49 | issue = 3 | pages = 658–71 | date = September 2006 | pmid = 16885670 | doi = 10.1097/00003081-200609000-00023 }}</ref>

==Contraindications==
It is recommended that medical treatment for ] with misoprostol should only be considered in people without the following contraindications: suspected ectopic pregnancy, use of non-steroidal drugs, signs of pelvic infections or sepsis, unstable hemodynamics, known allergy to misoprostol, previous caesarean section, mitral stenosis, hypertension, glaucoma, bronchial asthma, and remote areas without a hospital nearby.<ref name=":1" />


==Pharmacology== ==Pharmacology==
Misoprostol, a prostaglandin, binds to myometrial cells to cause strong myometrial contractions leading to expulsion of tissue. This agent also causes cervical ripening with softening and dilation of the cervix.


===Mechanism of action===
==Side effects and contraindications==
Misoprostol, a ], binds to myometrial cells to cause strong myometrial contractions leading to expulsion of tissue. This agent also causes cervical ripening with softening and dilation of the cervix. Misoprostol binds to and stimulates ]s, ] and ] but not ] and therefore is expected to have a more restricted range of physiological and potentially toxic actions than prostaglandin E<sub>2</sub> or other analogs which activate all four prostaglandin receptors.<ref name="pmid27940058">{{cite journal | vauthors = Moreno JJ | s2cid = 1513449 | title = Eicosanoid receptors: Targets for the treatment of disrupted intestinal epithelial homeostasis | journal = European Journal of Pharmacology | volume = 796 | pages = 7–19 | date = February 2017 | pmid = 27940058 | doi = 10.1016/j.ejphar.2016.12.004 }}</ref>
The most commonly reported ] of taking a misoprostol 200&nbsp;µg tablet by mouth four times a day to reduce the risk of NSAID induced gastric ulcers is ]. In clinical trials, an average 13% of patients reported diarrhea, which was dose-related and usually developed early in the course of therapy (after 13 days) and was usually self-limiting (often resolving within 8 days), but sometimes (in 2% of patients) required discontinuation of misoprostol.<!--
--><ref name="Cytotec USPI">{{cite web |author=] |month=September |year=2006 |title=Cytotec US Prescribing Information |url=http://www.pfizer.com/pfizer/download/uspi_cytotec.pdf |format=PDF|accessdate=2007-03-15}}</ref>


==Society and culture==
The next most commonly reported adverse effects of taking a misoprostol 200&nbsp;µg tablet by mouth four times a day to reduce the risk of NSAID induced gastric ulcers are: ], ], ], ], ], ], and ], but none of these adverse effects occurred significantly more often than when taking ]s.<!--
In August 2000, a letter from ], the inventor of the drug,<ref>{{Cite book | url=https://books.google.com/books?id=1A6kAgAAQBAJ&dq=%22inventor+of+misoprostol%22&pg=PA125 | title=Lipids in Health and Nutrition | isbn=9781845698386 | vauthors=Tyman JH | date=January 1999 | publisher=Elsevier | access-date=10 May 2022 | archive-date=29 June 2022 | archive-url=https://web.archive.org/web/20220629032411/https://books.google.com/books?id=1A6kAgAAQBAJ&dq=%22inventor+of+misoprostol%22&pg=PA125 | url-status=live }}</ref><ref>{{Cite book | url=https://books.google.com/books?id=Fm7nDwAAQBAJ&dq=%22misoprostol%22+%22searle%22+%22Rumsfeld%22&pg=PT129 | title=False Choices: The Faux Feminism of Hillary Rodham Clinton | isbn=9781784784638 | vauthors=Featherstone L | date=June 2016 | publisher=Verso Books | access-date=10 May 2022 | archive-date=29 June 2022 | archive-url=https://web.archive.org/web/20220629032412/https://books.google.com/books?id=Fm7nDwAAQBAJ&dq=%22misoprostol%22+%22searle%22+%22Rumsfeld%22&pg=PT129 | url-status=live }}</ref> generated controversy by warning against its use by pregnant women because of its ability to induce abortion, citing reports of maternal and fetal deaths when it was used to induce labor.<ref name="goldberg">{{cite journal | vauthors = Goldberg AB, Wing DA | title = Induction of labor: the misoprostol controversy | journal = Journal of Midwifery & Women's Health | volume = 48 | issue = 4 | pages = 244–8 | year = 2003 | pmid = 12867908 | doi = 10.1016/S1526-9523(03)00087-4 }}</ref> The ] holds that substantial evidence supports the use of misoprostol for induction of labor, a position it reaffirmed in response to the Searle letter.<ref>{{harvnb|Goldberg|Wing|2003}}, which cites:
--><ref name="Cytotec USPI"/>
:{{cite journal |author=American College of Obstetricians and Gynecologists |author-link=American College of Obstetricians and Gynecologists |title=Induction of labor with misoprostol |journal=ACOG Committee Opinion No. 228 |location=Washington, DC |date=November 1999}}
:{{cite journal |author=American College of Obstetricians and Gynecologists |author-link=American College of Obstetricians and Gynecologists |title=Response to Searle's drug warning on misoprostol |journal=ACOG Committee Opinion No. 248 |location=Washington, DC |date=November 1999}}</ref> It is on the ].<ref name="WHO22nd" />
Misoprostol should not be taken by pregnant women to reduce the risk of NSAID induced gastric ulcers because it increases uterine tone and contractions in pregnancy which may cause partial or complete abortions, and because its use in pregnancy has been associated with birth defects.<!--
--><ref name="Cytotec USPI"/><!--
--><ref name="Cytotec UK SPC">{{cite web |author=] |month=July |year=2004 |title=Cytotec UK SPC (Summary of Product Characteristics) |url=http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=9352 |accessdate=2007-03-15}}</ref>


A vaginal form of the medication is sold in the EU under the names Misodel<ref>{{Cite web |url=https://www.ema.europa.eu/en/documents/psusa/misoprostol-gynaecological-indication-labour-induction-list-nationally-authorised-medicinal-products/00010353/202005_en.pdf |title=List of nationally authorized medicinal products |access-date=29 June 2022 |archive-date=2 November 2021 |archive-url=https://web.archive.org/web/20211102122935/https://www.ema.europa.eu/en/documents/psusa/misoprostol-gynaecological-indication-labour-induction-list-nationally-authorised-medicinal-products/00010353/202005_en.pdf |url-status=live }}</ref> and Mysodelle<ref>{{Cite web |url=https://www.ema.europa.eu/en/documents/psusa/misoprostol-gynaecological-indication-labour-induction-list-nationally-authorised-medicinal-products/00010353/201905_en.pdf |title=List of nationally authorised medicinal products |access-date=26 June 2023 |archive-date=3 March 2022 |archive-url=https://web.archive.org/web/20220303093147/https://www.ema.europa.eu/en/documents/psusa/misoprostol-gynaecological-indication-labour-induction-list-nationally-authorised-medicinal-products/00010353/201905_en.pdf |url-status=live }}</ref> for use in labor induction.{{medcn|date=February 2020}}
One study suggests that misoprostol, if given vaginally rather than orally along with mifepristone to terminate a pregnancy, can increase the risk of serious infection with '']''.<ref>{{cite journal |author=KAronoff DM, Hao Y, Chung J, Coleman N, Lewis C, Peres CM, Serezani CH, Chen GH, Flamand N, Brock TG, Peters-Golden M |title=Misoprostol Impairs Female Reproductive Tract Innate Immunity against Clostridium sordellii |journal=J Immunol. |volume=180 |issue=12 |pages=8222–30. |date=June 15, 2008|pmid=18523288 |pubmed=in process |pmc=2667109}}</ref>


==References== ===Black market===
Misoprostol is used for ]s in Brazil, where ] 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 medical abortions. Failed misoprostol abortions are associated with birth defects in some cases.<ref>{{cite journal | vauthors = Costa SH, Vessey MP | s2cid = 30907894 | title = Misoprostol and illegal abortion in Rio de Janeiro, Brazil | journal = Lancet | volume = 341 | issue = 8855 | pages = 1258–61 | date = May 1993 | pmid = 8098402 | doi = 10.1016/0140-6736(93)91156-G }}</ref><ref>{{cite journal | vauthors = Coêlho HL, Teixeira AC, Cruz M, Gonzaga SL, Arrais PS, Luchini L, La Vecchia C, Tognoni G | display-authors = 6 | title = Misoprostol: the experience of women in Fortaleza, Brazil | journal = Contraception | volume = 49 | issue = 2 | pages = 101–10 | date = February 1994 | pmid = 8143449 | doi = 10.1016/0010-7824(94)90084-1 }}</ref><ref>{{cite journal | vauthors = Barbosa RM, Arilha M | title = The Brazilian experience with Cytotec | journal = Studies in Family Planning | volume = 24 | issue = 4 | pages = 236–40 | year = 1993 | pmid = 8212093 | doi = 10.2307/2939191 | jstor = 2939191 }}</ref><ref>{{cite journal | vauthors = Rocha J | title = Brazil investigates drug's possible link with birth defects | journal = BMJ | volume = 309 | issue = 6957 | pages = 757–8 | date = September 1994 | pmid = 7950553 | pmc = 2540993 | doi = 10.1136/bmj.309.6957.757a }}</ref><ref>{{cite journal | vauthors = Gonzalez CH, Vargas FR, Perez AB, Kim CA, Brunoni D, Marques-Dias MJ, Leone CR, Correa Neto J, Llerena Júnior JC, de Almeida JC | display-authors = 6 | title = Limb deficiency with or without Möbius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy | journal = American Journal of Medical Genetics | volume = 47 | issue = 1 | pages = 59–64 | date = August 1993 | pmid = 8368254 | doi = 10.1002/ajmg.1320470113 }}</ref> Low-income and immigrant populations in ] 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).<ref>{{cite news |author-link=John Leland (journalist) | vauthors = Leland J |url= https://www.nytimes.com/2005/10/02/weekinreview/02leland.html |title=Abortion Might Outgrow Its Need for Roe v. Wade |newspaper=] |date=2 October 2005 |access-date=6 March 2014 |url-status=live |archive-url=https://web.archive.org/web/20130518132249/http://www.nytimes.com/2005/10/02/weekinreview/02leland.html |archive-date=18 May 2013 }}</ref> The drug is readily available in Mexico.<ref name=NYT71313>{{cite news|title=In Mexican Pill, a Texas Option for an Abortion|url=https://www.nytimes.com/2013/07/14/us/in-mexican-pill-a-texas-option-for-an-abortion.html|access-date=14 July 2013|newspaper=The New York Times|date=13 July 2013| vauthors = Eckholm E |url-status=live|archive-url=https://web.archive.org/web/20130714154112/http://www.nytimes.com/2013/07/14/us/in-mexican-pill-a-texas-option-for-an-abortion.html|archive-date=14 July 2013}}</ref> Use of misoprostol has also increased in Texas in response to increased regulation of abortion providers.<ref>{{ cite news |url=https://www.theatlantic.com/health/archive/2014/06/the-rise-of-the-diy-abortion-in-texas/373240/ | vauthors = Hellenstein E |title=The Rise of the DIY Abortion in Texas |newspaper=The Atlantic |date=27 June 2014 |url-status=live |archive-url= https://web.archive.org/web/20170302015432/https://www.theatlantic.com/health/archive/2014/06/the-rise-of-the-diy-abortion-in-texas/373240/ |archive-date=2 March 2017 }}</ref> Following the United States Supreme Court decision of ], many states restricted access to legal abortion services, including medication abortion using misoprostol. As a result of these restrictions, it was reported that there was an increase in self-managed abortions by women in the United States. Many women purchased the pills from overseas online pharmacies or obtained misoprostol from Mexico.<ref>{{Cite news |vauthors=Sanger-Katz M, Miller CC |date=30 October 2022 |title=Legal Abortions Fell Around 6 Percent in Two Months After End of Roe |language=en-US |work=The New York Times |url=https://www.nytimes.com/2022/10/30/upshot/legal-abortions-fall-roe.html |access-date=8 February 2023 |issn=0362-4331 |archive-date=8 February 2023 |archive-url=https://web.archive.org/web/20230208135146/https://www.nytimes.com/2022/10/30/upshot/legal-abortions-fall-roe.html |url-status=live }}</ref>
{{Reflist|2}}

== References ==
{{Reflist}}


== External links and further reading ==
* an independent website containing dosage guidelines and advice on misoprostol use.
* A York University study outlining potential links toward autism.
{{Abortion}} {{Abortion}}
{{Prostaglandins}} {{Prostaglandins}}
{{Obstetric drugs}}
{{Drugs for peptic ulcer and GORD}} {{Drugs for peptic ulcer and GORD}}
{{Oxytocics}} {{Oxytocics}}
{{Prostanoidergics}}
* The Mechanism of Action and Pharmacology of Mifepristone, Misoprostol, and Methotrexate
{{Portal bar|Medicine}}


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