Misoprostol / Cytotec by drdoc on-line


1. What are Prostaglandin’s?

Prostaglandins (PGs) are a group of chemically related long-chained fatty acids that are synthesised by most cells in the body and exert a wide spectrum of local effects. Certain Prostaglandin’s are particularly active in the gastrointestinal tract where they are released locally.

2. What is Mucosal Protection?

Mucosal protection is the maintenance of the integrity of the gastrointestinal mucosa in the presence of endogenous aggressive factors, such as gastric acid, and exogenous aggressive factors, such as non-steroidal anti-inflammatory drugs. Components of mucosal defence are listed in the table below.

Components of the mucosal barrier

Mucus gel formation and secretion.
Bicarbonate secretion
Mucosal blood flow
Restricted routes of hydrogen ion permeation
Epithelial regeneration

Mucus provides a protective barrier, shielding the mucosa from Hydrogen ions as well as abrasion. Bicarbonate ions serve to neutralise gastric acid. Mucosal blood flow provides the mucosa with energy in the form of nutrients and removes excess Hydrogen ions. Finally, mucosal protection depends on rapid regeneration of epithelial tissue.

3. What are the effects of Prostaglandins on the Gastrointestinal Tract?

Certain Prostaglandins, particularly those of the E series, have a number of actions that protect the gastro-duodenal mucosa against numerous aggressive factors, thereby maintain mucosal integrity.

These actions include

mucus secretion
bicarbonate ion secretion
mucosal blood flow
gastric acid secretion

4. What is Cytotec®?

Cytotec® (Misoprostol) is a synthetic analogue of Prostaglandin E1 (PGE1). Like endogenous PGE1, Cytotec® exerts a protective effect on the gastrointestinal mucosa by increasing mucus and bicarbonate ion secretion and by increasing mucosal blood flow. In addition, Cytotec® inhibits acid secretion.

Naturally occurring PGE1 is ineffective after oral administration because it is unstable in an acid environment; it is also quickly degraded when administered parenterally, giving it no practical clinical utility. However, the structural modifications to naturally occurring PGE1 that led to the development of Cytotec® resulted in an orally active drug with a duration of action that makes it clinically useful.

5. Is Cytotec®‘s action a local response or is it dependent on absorption into the systemic circulation?

Cytotec® (Misoprostol) acts locally on the parietal cell to decrease acid secretion. It also exhibits local mucosal protection by supplying an exogenous source of Prostaglandin’s.
The principal active metabolite (Misoprostol acid) is rapidly metabolised and absorbed following oral administration.


6. What is the Incidence of Ulcer during Chronic NSAID Use?

Observations reported from a variety of clinical trials indicate that the incidence of peptic ulceration during Chronic NSAID use is substantial - depending on the study design, between 22% and 60% of patients.

7. Are there Differences in GI Damage between Younger and Older Patients Receiving NSAID Therapy?

There are definitely differences in the gastrointestinal impact of NSAID therapy on younger versus older patients. In a case-control study, the risk of NSAID-associated bleeding ulcer was greater in patients 60 years of age or older. There is an increasing incidence of NSAID-associated bleeding ulcer with advancing age: only 6% of those between 15 and 44 years of age to 37% of patient 75 and older. Analysis of attributable risk indicated that approximately 22% of bleeding ulcer cases were attributed to NSAID use in patients 60 years of age and older.

The results of clinical studies of Cytotec® indicate that no significantly different responses to safety and efficacy of therapy with Cytotec® were observed in elderly patients. These data suggest that dosage adjustments in the elderly are unnecessary.

8. What is the Mechanism of Effect of NSAID on the Gastrointestinal Tract?

Because of their anti-inflammatory properties, NSAIDs (including aspirin) are widely used to reduce pain and swelling. However, in the gastrointestinal tract, PGEs are also involved in mucosal protection. Thus, by inhibiting the formation of PGEs, NSAIDs reduce the protective ability of the gastrointestinal mucosa.

Aspirin and other NSAIDs also exert topical damaging effects on the gastrointestinal tract, an effect that is independent of NSAID inhibition of cyclooxygenase activity.

9. Are GI Symptoms Predictive of Lesions in Patients Taking NSAIDs?

NSAID-treated patients do not necessarily have symptoms even though gastropathy (ie, injury to the gastric mucosa) is present.


10. Can Concomitant Administration of Cytotec® with NSAIDs be used to Prevent or Treat NSAID-induced GI Mucosal Damage?

Several double-blind, placebo-controlled clinical trials have demonstrated that concomitant use of Cytotec® (Misoprostol) and NSAIDs can protect the GI Mucosa against NSAID-induced damage.

11. Does Concomitant Administration of Cytotec® and NSAIDs Interfere with the Efficacy of the NSAIDs?

In a study of 239 patients with rheumatoid Arthritis who were taking NSAIDs, 19 Rheumatoid Arthritis variables were analysed to examine Rheumatic Activity. Among 106 patient’s who received Cytotec®, no evidence of interference by Cytotec® with the anti-rheumatoid effects of the NSAID was observed.

12. What is Cytotec® Recommended Dosage for Preventing NSAID Damage?

Based on clinical studies, the recommended dosing regimen for prevention of NSAID-induced ulcers, erosions, and lesions is Cytotec® 800ug per day in four divided doses co-administered with continuing NSAID therapy if appropriate, with meals and at bedtime.

In South Africa - it is registered for 200mcg twice daily use.

13. Can Cytotec® be Concomitantly Administered with NSAIDs for Long-term Therapy?

Cytotec® had no influence on the absorption, metabolism, or excretion of a variety of other drugs including NSAIDs.

14. Should Cytotec® and NSAIDs be used Concomitantly in all Patients who Require Chronic NSAID Therapy?

In studies of regular NSAID users, 20% to 25% developed ulcers in three months. Therefore, any patient who cannot tolerate major complications of NSAID therapy, such as GI bleeding or perforation, is a candidate for co-adminstration of Cytotec®.
Patients with a history of NSAID-induced lesions or ulcer disease, and the elderly, seem to be at a greater risk of developing NSAID-induced complications.

15. How does Cytotec® Compare with Cimetidine in Preventing NSAID-induced GI Mucosal Damage?

In a double-blind, randomised study, the protective effects of Cimitidine vs Placebo were studied in patients with Arthritis who were using a variety of NSAIDs. Cimetidine failed to heal or protect the GI Mucosa in these patients during the eight-week treatment phase and the ten-month maintenance phase of the study.

16. How does Cytotec® Compare with Ranitidine in Protecting the Gastric Mucosa from NSAID-induced damage?

There are no direct comparative trials of Cytotec® and Ranitidine. However, in clinical studies comparing Ranitidine to Placebo, Ranitidine did not protect the Gastric Mucosa from damage induced by NSAIDs.


17. What are the Most Common Side Effects Associated with Cytotec® Therapy?

The most common side effect associated with Cytotec® therapy in clinical trials was diarrhoea, which is a natural response to the intestinal smooth muscles to the increased level of Prostaglandin’s. In clinical trials, diarrhoea occurred in approximately one tenth of patients. It was usually mild and self-limiting, resolving within a few days despite continued therapy. Cytotec® is to be dosed with meals and at bedtime, which will minimise this side effect.

18. Can Cytotec® be used in patients with Compromised Liver or Kidney Function? How does this compare with H2-receptor Antagonists?

Cytotec® (Misoprostol) is metabolised by fatty acid oxidising systems found in organs throughout the body. Its metabolism and plasma levels are therefore unlikely to be affected markedly in renal dysfunction or hepatic impairment. This suggests that the drug can be safely administered to patients with hepatic or renal impairment without the need for dosage adjustment.

19. Can Cytotec® be used in Pregnant or Nursing Women?

Cytotec® may endanger a pregnancy, and its effects on developing human foetus are not known. Therefore, Cytotec® should not be used in pregnant women. Women should be advised not to become pregnant while taking Cytotec®. If a woman becomes pregnant whilst taking Cytotec®, use of the product should be discontinued.
Although it is not known whether Cytotec® is excreted in human milk, Cytotec® should not be administered to nursing mothers.

20. Are There any Known Drug Interactions with Cytotec®?

In clinical trials, there was no evidence of interaction between Cytotec® and cardiac, gastrointestinal, pulmonary, or central nervous system drugs Decreased bioavailability of Misoprostol Acid was observed with high doses of antacid. However, low doses of antacids administered during ulcer healing trials had no effect on the efficacy of Cytotec®

Back to Drugs page
Back to NSAID's page
Back to Arthrotec Page
Back to drdoc on-line homepage

The webpage was put up by drdoc on-line in his personal capacity
on-line is not connected with the Pharmacia corporation / Searle Monsanto group.
The use of the logos and product information
do not constitute support by Pharmacia corporation / Searle for the website

The logos are copyright of Pharmacia corporation