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Misoprostol

Classification: B

Drug products: Angusta, Arthrotec forte, Arthrotec®, Arthrotec® forte, Cytotec, Cytotec®, Diklofenak/Misoprostol Actavis, Medabon, Misodel, Misofar

ATC code: A02BB01, G02AD06, G03XB51, M01AB55, M01BX

Substances: misoprostol

Summary

Misoprostol have both sex-specific use in laboring women or for termination of early pregnancy and a non-sex specific use in preventing and treating gastroduodenal ulcers and erosions in men and women on NSAID treatment. Data on sex difference for the latter indication is very limited.

Use of misoprostol to prevent NSAID-induced ulcers should be avoided in women of childbearing age. More information can be found in Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

The present evidence concerning differences between men and women on the indications used in both sexes is very limited and does not motivate differentiation in dosing or treatment. However, the risk in pregnant women needs to be considered.

Additional information

Misoprostol is an oral synthetic prostaglandin E1 analog with various indications. It is used in both men and women for prevention of NSAID-induced gastropathy . In women, misoprostol in combination with mifepristone (RU-486) is used for termination of early pregnancy [1-3]. Misoprostol alone can also be used for cervical ripening and labor induction, to prevent postpartum hemorrhage [1-3] although these indications are not approved by FDA [2].

Pharmacokinetics and dosing

No studies with clinically relevant sex analysis regarding the pharmacokinetics or dosing of misoprostol have been found.

Effects

The effect of misoprostol in gastroduodenal protection of NSAID induced ulcers or erosions have been shown in several studies including 35-76% women [4]. Relevant sex analyses have not been found. A database study including data from three large multicenter trials of healing of gastroduodenal ulcers with omeprazole or misoprostol (655 men, 1134 women, of whom 165 men and 138 women were treated with misoprostol) found more men (29%) to have had a duodenal ulcer only compared to women (16%). In women, duodenal ulcers were more common [5]. The overall chance of treatment success was lower in men (OR 0.79) (5)[5]. The original publication of the effect of misoprostol lacks a relevant sex analysis [6].

Adverse effects

No studies with a clinically relevant sex analysis regarding adverse effects of misoprostol have been found.

Reproductive health issues

Misoprostol has a boxed warning that administration to women who are pregnant can cause birth defects, abortion, premature birth or uterine rupture [7]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

A small study in healthy volunteers (11 men, 9 women) investigating the immunosuppressive effect of misoprostol found that misoprostol treatment increased levels of Interleukin 4 in men but decreased the level in women (8)[8]. Levels of Interferon gamma was more reduced in women compared to men [8].

Two French studies using questionnaires on GPs attitudes to prescription of gastroprotective agents together with NSAID show contradictory results. One showed that women were perceived to have a greater need [9], one published almost a decade later showed no perceived correlation between risk and patient’s sex [10]. A large North-American study in patients with rheumatoid arthritis (2570 men, 6266 women) found no correlation between patient’s sex and the risk of gastrointestinal complications [11].

Updated: 2019-03-13

Date of litterature search: 2017-07-12

References

  1. Cytotec (misoprostol). Summary of Product Characteristics. Medical Products Agency (MPA); 2012.
  2. Physicians' Digital Reference. http://www.pdr.net. [cited 2017-07-12]. länk
  3. CYTOTEC (misoprostol). Summary of Product Characteristics. http://www.medicines.org.uk/emc [cited 2017-07-12]
  4. Leontiadis GI, Sreedharan A, Dorward S, Barton P, Delaney B, Howden CW et al. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding. Health Technol Assess. 2007;11:iii-iv, 1-164. PubMed
  5. Hawkey CJ, Wilson I, Naesdal J, Långström G, Swannell AJ, Yeomans ND. Influence of sex and Helicobacter pylori on development and healing of gastroduodenal lesions in non-steroidal anti-inflammatory drug users. Gut. 2002;51:344-50. PubMed
  6. Hawkey CJ, Karrasch JA, Szczepañski L, Walker DG, Barkun A, Swannell AJ et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group. N Engl J Med. 1998;338:727-34. PubMed
  7. Misoprostol (misoprostol) DailyMed. DailyMed [www]. US National Library of Medicine. [updated 2016-02-12, cited 2017-07-12]. länk
  8. Waiser J, Böhler T, Stoll J, Schumann B, Budde K, Neumayer HH. The immunosuppressive potential of misoprostol--efficacy and variability. Clin Immunol. 2003;109:288-94. PubMed
  9. Bergmann JF, Pichot L, de Pouvourville G, Chassany O, Caulin C, Segrestaa JM. [Prevention of gastroduodenal lesions induced by non-steroidal anti-inflammatory agents Economic analysis from a survey of 356 physicians]. Presse Med. 1992;21:979-82. PubMed
  10. Clinard F, Bardou M, Sgro C, Lefevre N, Raphael F, Paille F et al. Non-steroidal anti-inflammatory and cytoprotective drug co-prescription in general practice A general practitioner-based survey in France. Eur J Clin Pharmacol. 2001;57:737-43. PubMed
  11. Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:241-9. PubMed

Authors: Mia von Euler, Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson