Misoprostol
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| Non-proprietary name | Misoprostol | ||||||||||||||||||
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| Molecular formula | C 22 H 38 O 5 | ||||||||||||||||||
| Brief description |
colorless to yellowish oil, hygroscopic. |
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| Drug class |
E 1 - prostaglandin |
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| properties | |||||||||||||||||||
| Molar mass | 382.54 g mol −1 | ||||||||||||||||||
| solubility |
practically insoluble in water, soluble in 96% ethanol |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Misoprostol is a synthetically produced derivative of the naturally occurring tissue hormone prostaglandin E 1 . It is used as a medicinal substance in the therapy and prevention of gastric and duodenal ulcers and in various areas of application in gynecology and obstetrics .
Stereochemical structure
Misoprostol is a synthetically produced derivative of prostaglandin E 1 and has four chiral centers.
The substance used pharmaceutically is an equimolar mixture of the two pairs of enantiomers
- (8 R , 11 R , 12 R , 13 E , 16 S ) and (8 S , 11 S , 12 S , 13 E , 16 R ) as well
- (8 R , 11 R , 12 R , 13 E , 16 R ) and (8 S , 11 S , 12 S , 13 E , 16 S ).
The (8 R , 11 R , 12 R , 13 E , 16 S ) stereoisomer is mainly effective .
Effects
As a prostaglandin analogue, misoprostol acts on the prostaglandin receptors of the parietal cells and inhibits acid and pepsin secretion in the stomach . It also supports the defense mechanisms of the gastric and intestinal mucosa by promoting the protective bicarbonate and mucus production. This can reduce the damage to the stomach or duodenum caused by overproduction of acid or pain medication .
Misoprostol causes the muscles of the uterus to contract .
Misoprostol is a prodrug and is rapidly absorbed after oral administration. The pharmacologically active metabolite misoprostolic acid is produced by biotransformation , with maximum plasma concentrations occurring within 15 to 30 minutes. The plasma elimination half-life is 20 to 40 minutes.
application areas
Gastric and duodenal ulcers
Misoprostol is approved as a finished medicinal product for the prevention and treatment of drug-related damage to the mucous membrane or ulcers of the stomach and duodenum, which can arise when taking non-steroidal anti-inflammatory drugs and the administration of which can neither be discontinued nor the dose reduced.
Because of the effect on the uterine muscles, it may only be used if pregnancy is excluded. In women of childbearing age, the active ingredient may only be used in this application, if a reliable method of contraception is used because of the exposure to misoprostol in the first trimester increased risk of malformations of the fetus has been reported. Misoprostol should not be taken during breastfeeding as it passes into breast milk.
The risk of abuse was that pregnant women could have their family doctor prescribe misoprostol on the pretext of stomach problems due to the use of painkillers , but then took the drug for illegal abortion.
Gynecology, obstetrics
Other areas of application are in gynecology and obstetrics. After childbirth, misoprostol is used to treat bleeding complications . It is also used to induce labor from the 36th week of pregnancy, to induce a restrained miscarriage and to support the medical abortion in the first and second third ( trimester ) of pregnancy. A medical termination of pregnancy is carried out through the administration of mifepristone , two days later misoprostol is given.
Because of these important indications, the drug is on the WHO list of Essential Medicines . After criticism that he was not on this list for bleeding complications after childbirth, this use has since been included, but only in case oxytocin should not be available. For gynecological and obstetric applications, finished medicinal products containing misoprostol are only approved in a limited number of countries, so they are largely used in off-label use , including in Germany. Misoprostol is the only prostaglandin that can be administered orally in these indications .
In 2020, Cytotec got into the media after research by report Munich and the Süddeutsche Zeitung , according to which serious incidents had occurred in Germany and France after improper use for induction of labor (off label). In Germany and France, therefore, lawsuits are pending before the courts. Some foreign authorities expressly refer to the potential occurrence of uncontrollable uterine contractions ("contractions"), the manufacturer Pfizer states that there are insufficient studies on the use of Cytotec . The German gynecological associations agree with a press release from the German Society for Obstetrics and Gynecology. V. (DGGG) opposes that misoprostol is administered in lower doses to induce labor than is contained in Cytotec and that it has been investigated in numerous studies in vaginal and oral administration. Misoprostol is used in almost all high-ranking perinatal centers and there are also approvals for induction of labor with misoprostol in other countries. On the other hand, in March 2020, after receiving new reports of serious side effects in off-label use in obstetrics, the German drug authorities warned against using Cytotec outside of the approved area of application. The drug could not be dosed precisely enough due to its inadequate divisibility and the sublingual , buccal or rectal administration, which was also used in addition to the oral administration and which circumvented the first-pass effect , was not investigated as part of the approval by Cytotec . It is possible to switch to other suitable drugs that have been approved for induction of labor.
Experimental treatment of trigeminal neuralgia
In a small, open-label study in 2003, misoprostol was shown to be effective in the treatment of refractory trigeminal neuralgia in patients with multiple sclerosis .
Side effects
In the treatment of ulcers , the diarrhea which occurs in 13% of the cases should be emphasized , which leads to a discontinuation of the therapy in 0.5%. Furthermore, nausea and abdominal pain as well as headaches and dizziness can occur. Cardiovascular effects practically do not occur.
After administration of misoprostol in the second or third trimester of pregnancy, uterine rupture has been observed in rare cases , especially in women who had already given birth or who had a scar after a previous caesarean section.
Trade names
- Gynecology
- Induction of labor : Angusta (DK, SE, FI, NO, FR), Misodel Vaginalinsert (CH, in D since 2019 except sales)
- Abortion (in accordance with the applicable laws and regulations): MisoOne (D, CH), Topogyne (AT, UK)
- Ulcer prophylaxis
- Cytotec (CH), Cyprostol (A). In Germany, the manufacturer removed Cytotec from the market in 2006 on the grounds that it was frequently misused for abortion.
- in combination with Diclofenac : Arthotec (D) Arthrotec (A, CH and other countries)
Web links
- Entry on misoprostol at Vetpharm, accessed August 11, 2012.
Individual evidence
- ↑ a b c d K. Hardtke et al. (Ed.): Commentary on the European Pharmacopoeia Ph. Eur. 5.3, Misoprostol. Loose-leaf collection, 25th delivery 2006, Wissenschaftliche Verlagsgesellschaft Stuttgart.
- ↑ a b European Pharmacopoeia. 6th edition, Deutscher Apotheker Verlag, Stuttgart 2008, ISBN 978-3-7692-3962-1 , pp. 3292–3294.
- ↑ a b c Data sheet Misoprostol ≥ 99% (TLC) from Sigma-Aldrich , accessed on April 10, 2011 ( PDF ).
- ↑ technical information Cyprostol tablets, as of March of 2009.
- ↑ a b Technical information Cytotec 200, as of November 2008.
- ↑ a b Resolution of the CMDh coordination group of the HMA , dated February 21, 2018.
- ↑ G. Geisslinger et al .: Mutschler drug effects: Pharmakologie - Klinische Pharmakologie - Toxikologie , 11th edition, 2019. P. 80.
- ^ WHO Model Lists of Essential Medicines
- ↑ Experts seek WHO nod for postpartum haemorrhage drug. IRIN humanitarian news and analysis, March 16, 2011, accessed March 21, 2011 .
- ↑ Misoprostol Approved. In: misoprostol.org. Accessed September 24, 2017.
- ↑ Use of prostaglandins in obstetrics and gynecology of the Association of Scientific Medical Societies (AWMF), accessed August 10, 2009.
- ↑ Working paper: Off-Label Use in Gynecology and Obstetrics of the Working Group of Scientific Medical Societies (AWMF), viewed December 25, 2015.
- ↑ Induction of labor: small tablet, big risk. In: tagesschau.de. February 11, 2020, accessed February 11, 2020 .
- ^ Opinion on reporting on "Cytotec for induction of labor" , DGGG PM of February 13, 2020, accessed on February 15, 2020.
- ↑ How dangerous is Cytotec during childbirth ; SPON of February 14, 2020, accessed on February 15, 2020.
- ^ A b D. Moll: Dangerous or lifesaver for women? Deutsche Apothekerzeitung (DAZonline), February 13, 2020.
- ↑ Rote-Hand-Brief on Misoprostol: Risks in connection with an application for induction of labor outside the approval ("off-label-use") , Federal Institute for Drugs and Medical Devices (BfArM), March 16, 2020.
- ↑ DMKG study group: Misoprostol in the treatment of trigeminal neuralgia associated with multiple sclerosis . In: Journal of Neurology . tape 250 , no. 5 , 2003, p. 542-545 , doi : 10.1007 / s00415-003-1032-1 , PMID 12736732 .
