Misoprostol, is used for reducing the risk of nonsteroidal anti-inflammatory agent (NSAIA)-induced gastric ulcer in patients at high risk of developing complications from these ulcers and in patients at high risk of developing gastric ulceration.Misoprostol has been used for the short-term treatment of active duodenal ulcer and for the short-term treatment of active, benign gastric ulcer. Misoprostol also has been used as maintenance therapy following healing of gastric ulcer to reduce ulcer recurrence.
Misoprostol is used as an adjunct to mifepristone for the medical termination of intrauterine pregnancy (i.e., medical abortion). The drug has been used for induction of labor and for treatment of serious postpartum hemorrhage in the presence of uterine atony.
Prevention of NSAIA-induced Ulcers
Misoprostol is used for reducing the risk of NSAIA-induced gastric ulcers in patients at high risk of developing complications (e.g., bleeding, perforation, death) from these ulcers, such as patients with a concomitant debilitating disease and geriatric patients, and in patients at high risk of developing gastric ulceration, such as those with a history of upper GI ulcer.While the drug also has been used for the prevention of NSAIA-induced duodenal ulcers in a limited number of patients, current evidence is insufficient to establish efficacy in these patients.
Serious adverse GI effects (e.g., bleeding, ulceration, perforation) can occur at any time in patients receiving chronic NSAIA therapy, and such effects may not be preceded by warning signs or symptoms. Results of studies to date are inconclusive concerning the relative risk of various NSAIAs in causing serious GI effects. In patients receiving prototypical NSAIAs and observed in clinical studies of several months' to 2-years' duration, symptomatic upper GI ulcers, gross bleeding, or perforation appeared to occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of those treated for 1 year. These trends continue with long-term therapy and increase the likelihood of a serious GI event occurring at some time during the course of therapy. Studies have shown that patients with a history of peptic ulcer disease and/or GI bleeding who are receiving NSAIAs have a greater than tenfold higher risk for developing GI bleeding than patients without these risk factors. In addition to a history of ulcer disease, pharmacoepidemiologic studies have identified several comorbid conditions and concomitant therapies that may increase the risk for GI bleeding, including concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAIA therapy, smoking, alcoholism, older age, and poor general health status. In addition, geriatric or debilitated patients appear to tolerate GI ulceration and bleeding less well than other individuals, and most spontaneous reports of fatal NSAIA-induced GI effects have been in such patients. Therefore, consideration can be given to concomitant preventive therapy with misoprostol in these and other patients deemed at high risk of developing complications resulting from NSAIA-induced gastric ulcer or at high risk of developing such ulcers.
Efficacy of misoprostol for the prevention of NSAIA-induced gastric ulcer has been established principally in short-term studies (up to 3 months' duration). Therefore, although continuous misoprostol therapy for the duration of NSAIA use currently is recommended by the manufacturer, the long-term safety and efficacy and optimum duration of misoprostol therapy in patients receiving NSAIAs chronically remain to be established. In addition, although NSAIA-induced gastric injury is asymptomatic in most patients, most studies conducted to date have included only patients with symptomatic injury. It also should be recognized that while misoprostol is intended for use in the prevention of NSAIA-induced gastric injury in patients at high risk of complications from such injury, efficacy of the drug in most high-risk patient groups has not been specifically established. Despite the lack of such data, however, high-risk patients are thought to be most likely to benefit from prophylactic therapy with misoprostol.
Misoprostol has reduced the rate of endoscopically documented NSAIA-induced gastroduodenal mucosal injury in healthy individuals. The drug also has reduced the rate of gastroduodenal ulcer formation in osteoarthritic patients with GI symptoms but no evidence of ulcer prior to initiation of misoprostol. Gastroduodenal mucosal injury also has been reduced and healing of gastroduodenal ulcer promoted in patients with rheumatoid arthritis who had GI symptoms and evidence of mucosal injury and/or ulcer when misoprostol was initiated. However, misoprostol does not appear to be effective in reducing associated GI symptoms (e.g., pain).
In several short-term (about 1-week duration) studies in a limited number of healthy individuals receiving a NSAIA (e.g., aspirin, ibuprofen, naproxen, tolmetin), reported rates of endoscopically documented gastric or duodenal mucosal injury were 10-30% in those receiving oral misoprostol dosages of 100 or 200 mcg 4 times daily and 70-75% in those receiving placebo. In a limited number of healthy individuals, misoprostol also has been more effective than sucralfate in preventing aspirin-induced gastroduodenal mucosal injury and more effective than cimetidine in preventing tolmetin-induced gastric but not duodenal mucosal injury.
In a multicenter controlled study in patients with osteoarthritis who were receiving chronic NSAIA therapy (e.g., 3 months or longer with ibuprofen, naproxen, or piroxicam) and had GI symptoms but no endoscopic evidence of gastric ulcer, 100 or 200 mcg of misoprostol 4 times daily reduced the rate of NSAIA-induced gastric ulcer formation; at 12 weeks, 21-30% of patients receiving placebo developed gastric ulcers while only 1.4-3 or 6-8% of patients receiving the 200- or 100-mcg regimen, respectively, developed such ulcers. However, the 100-mcg regimen was less effective than the 200-mcg regimen, producing a significant reduction in gastric ulcer formation compared with placebo in only one of the study groups. In addition, misoprostol was not effective in relieving associated GI symptoms (e.g., daytime or nocturnal abdominal pain, nausea, vomiting, anorexia) with either regimen.
In a study in patients with rheumatoid arthritis who were receiving aspirin therapy for at least 4 weeks and had GI symptoms and endoscopically confirmed gastric and/or duodenal injury, 8 weeks of concomitant misoprostol (200 mcg 4 times daily) therapy promoted gastroduodenal healing, including healing of ulcers. Healing of gastric or duodenal mucosal injury occurred at 8 weeks in 70 or 86%, respectively, of patients receiving misoprostol compared with 25 or 53%, respectively, of those receiving placebo, and healing of gastroduodenal ulcers occurred in 67% of patients receiving the drug compared with 26% of those receiving placebo. There was similar evidence of misoprostol-induced healing at 4 weeks. Misoprostol also appeared to prevent formation of new ulcers and did not interfere with the efficacy of aspirin as determined by relief of pain and stiffness, reduction of swelling, improvement of mobility and grip strength, or erythrocyte sedimentation rate (ESR).
For information on the use of misoprostol in fixed combination with diclofenac, a NSAIA,
Misoprostol has been used in the short-term treatment of active, benign, gastric ulcer. However, the drug does not appear to offer any superiority over H2-receptor antagonists and is less effective than these agents in relieving ulcer pain. Because misoprostol is associated with severe adverse effects (e.g., fetal mortality, premature birth, birth defects), it is not considered a drug of choice for the treatment of peptic ulcer disease (e.g., gastric ulcer) and is not included in the current American College of Gastroenterology (ACG) guidelines for the treatment of this condition.
Current epidemiologic and clinical evidence supports a strong association between gastric infection with H. pylori and the pathogenesis of gastric ulcers, and the ACG, National Institutes of Health (NIH), and most clinicians currently recommend that all patients with initial or recurrent gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection. The choice of a particular regimen should be based on the rapidly evolving data on optimal therapy, including consideration of the patient's prior exposure to anti-infective agents, the local prevalence of resistance, patient compliance, and costs of therapy.
(See Duodenal Ulcer: Acute Therapy, in Uses.)For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection, .
Misoprostol has been used in reduced dosage for up to 14 months in a limited number of patients as maintenance therapy following healing of active gastric ulcer to reduce ulcer recurrence. However, additional studies are needed to evaluate the safety and efficacy of maintenance therapy with the drug.
Misoprostol has been used for the short-term treatment of endoscopically or radiographically confirmed active duodenal ulcer. Limited data suggest that misoprostol also may be effective in some patients with duodenal ulcer refractory to H2-antagonist therapy. However, misoprostol does not appear to be effective in reducing daytime and nocturnal pain or antacid consumption in patients with duodenal ulcers; aluminum-containing antacids have been used concomitantly with the drug as needed for relief of pain.
Some clinicians state that misoprostol does not appear to offer any superiority over other existing antiulcer therapies for active duodenal ulcers in terms of healing efficacy, dosing schedule, or recurrence after treatment, but is less effective in relieving associated GI pain. Because misoprostol may represent a risk of uterine bleeding and/or abortion when inadvertently used by pregnant women, it is not considered a drug of choice for the treatment of peptic ulcer disease (e.g., duodenal ulcer) and is not included in the current ACG guidelines for the treatment of this condition.
Current epidemiologic and clinical evidence supports a strong association between gastric infection with Helicobacter pylori and the pathogenesis of duodenal and gastric ulcers; long-term H. pylori infection also has been implicated as a risk factor for gastric cancer. The ACG, NIH, and most clinicians currently recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection. Anti-H. pylori regimens that combine one or more anti-infective agents (e.g., clarithromycin, amoxicillin) with a bismuth salt and/or an antisecretory agent (e.g., omeprazole, lansoprazole, H2-receptor antagonist) have been used successfully for H. pylori eradication. The choice of a particular regimen should be based on the rapidly evolving data on optimal therapy, including consideration of the patient's prior exposure to anti-infective agents, the local prevalence of resistance, patient compliance, and costs of therapy. For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection, and .
Termination of Pregnancy
Misoprostol is used as an adjunct to mifepristone for medical termination of an intrauterine pregnancy. Although Pharmacia, the manufacturer of misoprostol, states that it has not conducted and does not intend to conduct research to support such usage, use of misoprostol with mifepristone for termination of pregnancy is included in the approved labeling of mifepristone in the US and in Europe, and the American College of Obstetricians and Gynecologists (ACOG) states that misoprostol is necessary for termination of pregnancy with mifepristone. For a complete discussion of the use of misoprostol with mifepristone for this indication,
Other Obstetric Uses
ACOG states that misoprostol has been used effectively (e.g., 25 mcg every 3-6 hours intravaginally using tablets formulated for oral administration) to improve cervical inducibility (cervical ''ripening'') in pregnant women with a medical or obstetric need for labor induction. Although Pharmacia, the manufacturer of misoprostol, states that it has not conducted and does not intend to conduct research to support use in pregnancy (e.g., labor induction), vaginal administration of misoprostol appears to be safe and effective for induction of labor in appropriately selected women with unfavorable cervices. However, such use in women with prior uterine surgery or cesarean section should be avoided because of the risk of possible uterine rupture.
Misoprostol also has been used for prevention or treatment of serious postpartum hemorrhage in the presence of uterine atony.
Misoprostol has been used in a limited number of patients for the management of fat malabsorption associated with cystic fibrosis, and for the management of hemorrhagic gastritis, reflux esophagitis, alcohol-induced gastritis, and NSAIA-induced nephropathy. The drug has been effective in some patients with these conditions, but further studies are needed.