misoprostol and Diarrhea

There is great controversy regarding the most effective route for cervical priming before diagnostic or operative hysteroscopy.. To evaluate the evidence from published randomized clinical trials (RCTs) about the efficacy and safety of oral vs vaginal misoprostol for cervical priming before hysteroscopy.. Electronic databases including PubMed, Cochrane Library, Scopus and Web of Science were searched using the relevant keywords.. All RCTs assessing the effect of oral vs vaginal misoprostol before hysteroscopy for cervical priming were considered. One hundred and ten studies were identified, of which eight studies were deemed eligible for this review.. The extracted outcomes were: cervical canal width, ease of dilatation, time for cervical dilatation and adverse effects (nausea, vomiting, diarrhoea, bleeding, fever, abdominal pain/uterine cramping and any complications during the procedure). All statistical analyses were completed using RevMan.. Eight RCTs with 768 patients were included in this meta-analysis. Cervical canal width did not differ significantly between the two routes of misoprostol administration [mean difference -0.25 mm, 95% confidence interval (CI) -0.92-0.42; p = 0.47]. However, the vaginal route was significantly superior to the oral route for reducing the time for cervical dilatation (standardized mean difference 0.17, 95% CI 0.02-0.32; p = 0.03). No significant differences in adverse effects were found between the routes, except for diarrhoea which was significantly less prevalent with vaginal administration of misoprostol (risk ratio 2.48, 95% CI 1.17-5.26; p = 0.02).. Oral and vaginal administration of misoprostol before hysteroscopy were similar in terms of cervical canal width, ease of dilatation and various adverse effects, except that the vaginal route was associated with faster cervical dilatation and lower prevalence of diarrhoea.

Topics: Abdominal Pain; Administration, Intravaginal; Administration, Oral; Cervix Uteri; Diarrhea; Dilatation; Female; Humans; Hysteroscopy; Misoprostol; Oxytocics; Premedication; Randomized Controlled Trials as Topic

Miscarriage occurs in 10% to 15% of pregnancies. The traditional treatment, after miscarriage, has been to perform surgery to remove any remaining placental tissues in the uterus ('evacuation of uterus'). However, medical treatments, or expectant care (no treatment), may also be effective, safe, and acceptable.. To assess the effectiveness, safety, and acceptability of any medical treatment for incomplete miscarriage (before 24 weeks).. We searched Cochrane Pregnancy and Childbirth's Trials Register (13 May 2016) and reference lists of retrieved papers.. We included randomised controlled trials comparing medical treatment with expectant care or surgery, or alternative methods of medical treatment. We excluded quasi-randomised trials.. Two review authors independently assessed the studies for inclusion, assessed risk of bias, and carried out data extraction. Data entry was checked. We assessed the quality of the evidence using the GRADE approach.. We included 24 studies (5577 women). There were no trials specifically of miscarriage treatment after 13 weeks' gestation.Three trials involving 335 women compared misoprostol treatment (all vaginally administered) with expectant care. There was no difference in complete miscarriage (average risk ratio (RR) 1.23, 95% confidence interval (CI) 0.72 to 2.10; 2 studies, 150 women, random-effects; very low-quality evidence), or in the need for surgical evacuation (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. For unplanned surgical intervention, we did not identify any difference between misoprostol and expectant care (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence).Sixteen trials involving 4044 women addressed the comparison of misoprostol (7 studies used oral administration, 6 studies used vaginal, 2 studies sublingual, 1 study combined vaginal + oral) with surgical evacuation. There was a slightly lower incidence of complete miscarriage with misoprostol (average RR 0.96, 95% CI 0.94 to 0.98; 15 studies, 3862 women, random-effects; very low-quality evidence) but with success rate high for both methods. Overall, there were fewer surgical evacuations with misoprostol (average RR 0.05, 95% CI 0.02 to 0.11; 13 studies, 3070 women, random-effects; very low-quality evidence) but more unplanned procedures (average RR 5.03, 95% CI 2.71 to 9.35; 11 studies, 2690 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. Nausea was more common with misoprostol (average RR 2.50, 95% CI 1.53 to 4.09; 11 studies, 3015 women, random-effects; low-quality evidence). We did not identify any difference in women's satisfaction between misoprostol and surgery (average RR 1.00, 95% CI 0.99 to 1.00; 9 studies, 3349 women, random-effects; moderate-quality evidence). More women had vomiting and diarrhoea with misoprostol compared with surgery (vomiting: average RR 1.97, 95% CI 1.36 to 2.85; 10 studies, 2977 women, random-effects; moderate-quality evidence; diarrhoea: average RR 4.82, 95% CI 1.09 to 21.32; 4 studies, 757 women, random-effects; moderate-quality evidence).Five trials compared different routes of administration, or doses, or both, of misoprostol. There was no clear evidence of one regimen being superior to another. Limited evidence suggests that women generally seem. The available evidence suggests that medical treatment, with misoprostol, and expectant care are both acceptable alternatives to routine surgical evacuation given the availability of health service resources to support all three approaches. Further studies, including long-term follow-up, are clearly needed to confirm these findings. There is an urgent need for studies on women who miscarry at more than 13 weeks' gestation.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Incomplete; Administration, Intravaginal; Administration, Oral; Diarrhea; Extraction, Obstetrical; Female; Gestational Age; Humans; Misoprostol; Nausea; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic; Vomiting; Watchful Waiting

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Chills; Congenital Abnormalities; Diarrhea; Drug Administration Schedule; Female; Fever; Gestational Age; Humans; Milk, Human; Misoprostol; Muscle Cramp; Nausea; Pregnancy; Uterine Hemorrhage; Vomiting

Diarrhoea is a relatively frequent adverse event, accounting for about 7% of all drug adverse effects. More than 700 drugs have been implicated in causing diarrhoea; those most frequently involved are antimicrobials, laxatives, magnesium-containing antacids, lactose- or sorbitol-containing products, nonsteroidal anti-inflammatory drugs, prostaglandins, colchicine, antineoplastics, antiarrhythmic drugs and cholinergic agents. Certain new drugs are likely to induce diarrhoea because of their pharmacodynamic properties; examples include anthraquinone-related agents, alpha-glucosidase inhibitors, lipase inhibitors and cholinesterase inhibitors. Antimicrobials are responsible for 25% of drug-induced diarrhoea. The disease spectrum of antimicrobial-associated diarrhoea ranges from benign diarrhoea to pseudomembranous colitis. Several pathophysiological mechanisms are involved in drug-induced diarrhoea: osmotic diarrhoea, secretory diarrhoea, shortened transit time, exudative diarrhoea and protein-losing enteropathy, and malabsorption or maldigestion of fat and carbohydrates. Often 2 or more mechanisms are present simultaneously. In clinical practice, 2 major types of diarrhoea are seen: acute diarrhoea, which usually appears during the first few days of treatment, and chronic diarrhoea, lasting more than 3 or 4 weeks and which can appear a long time after the start of drug therapy. Both can be severe and poorly tolerated. In a patient presenting with diarrhoea, the medical history is very important, especially the drug history, as it can suggest a diagnosis of drug-induced diarrhoea and thereby avoid multiple diagnostic tests. The clinical examination should cover severity criteria such as fever, rectal emission of blood and mucus, dehydration and bodyweight loss. Establishing a relationship between drug consumption and diarrhoea or colitis can be difficult when the time elapsed between the start of the drug and the onset of symptoms is long, sometimes up to several months or years.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Cardiovascular Agents; Cathartics; Diarrhea; Enterocolitis, Pseudomembranous; Humans; Misoprostol

Misoprostol, a synthetic prostaglandin E1, has been shown to reduce both gastric lesions and clinically relevant gastrointestinal events in patients taking NSAIDs. In patients with multiple risk factors gain in quality of life by avoidance of gastric ulcers seems to offset the loss in quality of life due to diarrhea, the most important misoprostol side effect. From a clinical-epidemiological point of view misoprostol prophylaxis thus seems reasonable in patients with multiple risk factors. Since non-use due to diarrhea varies highly among patients, individual preferences should be considered in the decision making process. From an economic point of view misoprostol prophylaxis seems justified in patients with multiple risk factors. In such patients misoprostol prophylaxis may indeed be cost-saving. However, this needs to be confirmed in further economic evaluations based on newly available effectiveness data and better data on patient preferences from large and representative samples.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Diarrhea; Drug Costs; Gastrointestinal Diseases; Humans; Misoprostol; Quality of Life; Risk Factors; Stomach Ulcer

Data from four double-blind studies of the treatment of patients with rheumatoid arthritis or osteoarthritis were combined. For 4 to 12 weeks, 747 patients received Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol, and 754 patients received 50 mg of diclofenac; the drugs were given twice or three times daily. The five most commonly reported adverse events were abdominal pain by 23.2% of the diclofenac/misoprostol patients and 19.8% of the diclofenac patients; diarrhea by 19.9% and 11.3%; nausea by 11.8% and 6.5%; dyspepsia by 11.2% and 7.8%; and flatulence by 8.0% and 3.1%. Other adverse events, reported by similar proportions of both treatment groups, included headache, gastritis, dizziness, vomiting, and constipation. In the diclofenac/misoprostol-treated patients, the abdominal pain and diarrhea were rated mild in 30.6% and 24.3%, moderate in 49.1% and 51.4%, and severe in 20.2% and 24.3%. Serious adverse events occurred in eight of the diclofenac/misoprostol-treated patients and in 13 of the diclofenac-treated patients; 12.6% and 10.1%, respectively, were withdrawn from the study because of adverse events. Results of laboratory tests of hepatic and renal function were similar in the two treatment groups.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Constipation; Diarrhea; Diclofenac; Dizziness; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Misoprostol; Osteoarthritis; Pain; Vomiting

Misoprostol is an E1 prostaglandin analog. Most of the other synthetic prostaglandins that are being studied in advanced clinical trials for gastrointestinal diseases are E2 derivatives. Misoprostol has shown a dose-related antisecretory effect that lasted 3-5.5 hr. In addition, animal studies have shown cytoprotective properties that are being confirmed in clinical studies. Ulcer-healing trials using four times daily dosing appear to parallel the antisecretory dose-response curve up to a dose of 200 micrograms qid. Evidence presented in this supplement suggests a further increase in healing-rate response at 300 micrograms misoprostol qid. The misoprostol healing rates obtained in duodenal ulcer and gastric ulcer therapy at 200 micrograms qid are not significantly different from those seen in the same studies with cimetidine at a dose of 300 mg qid. No significant rebound in recurrence has been observed during follow-up for 12 months after short-term 100- and 200-micrograms qid misoprostol treatment. The most frequent adverse effects are dose-related diarrhea and abdominal cramping, which are transient in most patients and have not caused a significant problem in clinical use. There is also a tropic effect on the pregnant uterus, which was observed in a special pharmacologic clinical study. No significant abnormalities have been detected in clinical laboratory tests or gastric biopsies. There have also been no adverse effects noted on blood pressure, pulse, platelets, the immune system, pulmonary function, gastrointestinal hormones, or the endocrine system. These previously discussed characteristics of misoprostol, and current data, suggest that this prostaglandin E1 derivative may be an important addition to the treatment of peptic ulcer disease.

Topics: Alprostadil; Anti-Ulcer Agents; Cimetidine; Clinical Trials as Topic; Diarrhea; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Humans; Immune System; Misoprostol; Peptic Ulcer; Platelet Aggregation; Recurrence; Uterus

To compare the physical and emotional effects of two medical protocols for induced abortion during the second trimester.. The present study was part of a prospective randomized controlled trial comparing mifepristone followed by oxytocin or misoprostol that was conducted at the Hadassah Hebrew University Medical Center, Jerusalem, Israel, from January 10, 2009, to February 22, 2012. Inclusion criteria were pregnancy (14-24weeks), epidural analgesia, and medical induction of abortion (either elective or following missed abortion). A structured questionnaire was used to assess the participants' physical symptoms and emotional responses. The primary outcome for the present analysis was the degree of physical symptoms reported.. Overall, 68 women in the oxytocin group and 67 in the misoprostol group received epidural analgesia and completed the questionnaire. As assessed using a five-point Likert scale, women in the misoprostol group were more likely than those in the oxytocin group to experience diarrhea (1.34±0.84 vs 1.10±0.55; P=0.05) and shivers (3.03±1.75 vs 1.75±1.21; P<0.001). No other between-group differences were detected for the physical or emotional variables evaluated.. Differences in physical symptoms experienced by the two treatment groups did not influence the participants' subsequent emotional response. ClinicalTrials.gov: NCT00784797.

Topics: Abortifacient Agents; Abortion, Induced; Administration, Intravaginal; Administration, Intravenous; Administration, Oral; Adult; Diarrhea; Emotions; Female; Humans; Israel; Mifepristone; Misoprostol; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Prospective Studies; Psychiatric Status Rating Scales; Shivering

To compare the efficacy of oral misoprostol with that of oxytocin for active management of the third stage of labor (AMTSL).. A double-blind randomized control trial was undertaken at a center in Ilorin, Nigeria, between January and June 2013. Every other eligible patient (in the first stage of labor at term, to have a spontaneous vaginal delivery, and no/low risk of postpartum hemorrhage [PPH]) were randomly assigned with computer-generated random numbers to receive oral misoprostol (600μg) plus placebo injection or oral placebo plus oxytocin injection (1mL of 10IU) in the third stage of labor. The primary outcome was amount of blood loss during delivery.. Mean postpartum blood loss was 325.85±164.72mL in the 100 patients given misoprostol and 303.95±163.33mL in the 100 patients given oxytocin (P=0.391). PPH (≥500mL blood loss) was recorded in 15 (15.0%) patients given misoprostol and 14 (14.0%) given oxytocin (P=0.841). Shivering, pyrexia, and diarrhea were all significantly more common in the misoprostol group (P<0.01 for all).. The efficacy of oral misoprostol was similar to that of intramuscular oxytocin. Adverse effects associated with misoprostol were transient and self-limiting. Thus, oral misoprostol is efficacious and a good alternative to oxytocin for AMTSL. Pan African Clinical Trials Registry:PACTR201407000825227.

Topics: Administration, Oral; Adult; Blood Volume; Diarrhea; Double-Blind Method; Female; Fever; Hospitals; Humans; Injections, Intramuscular; Labor Stage, Third; Misoprostol; Nigeria; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Shivering; Young Adult

Dysregulated cytokine metabolism plays a critical role in the pathogenesis of many forms of liver disease, including alcoholic and non-alcoholic liver disease. In this study we examined the efficacy of Misoprostol in modulating LPS-inducible TNFα and IL-10 expression in healthy human subjects and evaluated molecular mechanisms for Misoprostol modulation of cytokines in vitro. Healthy subjects were given 14day courses of Misoprostol at doses of 100, 200, and 300μg four times a day, in random order. Baseline and LPS-inducible cytokine levels were examined ex vivo in whole blood at the beginning and the end of the study. Additionally, in vitro studies were performed using primary human PBMCs and the murine macrophage cell line, RAW 264.7, to investigate underlying mechanisms of misoprostol on cytokine production. Administration of Misoprostol reduced LPS inducible TNF production by 29%, while increasing IL-10 production by 79% in human subjects with no significant dose effect on ex vivo cytokine activity; In vitro, the effect of Misoprostol was largely mediated by increased cAMP levels and consequent changes in CRE and NFκB activity, which are critical for regulating IL-10 and TNF expression. Additionally, chromatin immunoprecipitation (ChIP) studies demonstrated that Misoprostol treatment led to changes in transcription factor and RNA Polymerase II binding, resulting in changes in mRNA levels. In summary, Misoprostol was effective at beneficially modulating TNF and IL-10 levels both in vivo and in vitro; these studies suggest a potential rationale for Misoprostol use in ALD, NASH and other liver diseases where inflammation plays an etiologic role.

Topics: Abdominal Pain; Animals; Anti-Ulcer Agents; Cell Line; Cells, Cultured; Cyclic AMP; Cytokines; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Gene Expression; Humans; Interleukin-10; Leukocytes, Mononuclear; Lipopolysaccharides; Liver Diseases; Macrophages; Male; Mice; Misoprostol; Nausea; Signal Transduction; Tumor Necrosis Factor-alpha

To compare complication rates, efficacy and acceptability of buccal misoprostol to laminaria for cervical preparation before dilation and evacuation (D&E) in South Africa.. We performed a randomized, single-blind trial comparing buccal misoprostol 400 mcg (1-2 doses, administered at least 3 h before D&E) to laminaria inserted the day before D&E among women at 13-19 weeks gestation. The primary outcome was expulsion of the fetus prior to surgery; secondary outcomes included other complications, need for mechanical dilation, procedure duration, side effects and satisfaction. Required sample size was 176 to detect a difference in expulsion of 20% to 5%, with a two-sided alpha of 0.05 and 80% power.. Due to slow enrollment and low incidence of primary outcome, the study was stopped early. One hundred fifty-nine women were randomized, and 156 received treatment (78 in each group). Mean gestational age was 14.8 weeks (range, 13.0-18.6 weeks). Complications were rare and did not differ by group [three in each group; odds ratio (OR), 1; 95% confidence interval (CI), 0.20-5.11]; this included two expulsions in the misoprostol group (2.6%). Misoprostol participants were more likely to require mechanical dilation compared to those receiving laminaria (35% vs. 8%; OR, 6.4; 95% CI, 2.4-16.5). The proportion of women reporting each side effect was similar except for diarrhea (21.3% in misoprostol group vs. 5.2% in laminaria group, p=0.004). Procedure time and satisfaction did not differ between groups.. Both misoprostol and laminaria are associated with a low complication rate in this setting, although misoprostol requires more mechanical dilation and causes more diarrhea.. Cervical preparation using either laminaria or misoprostol can be safely used before D&E up to at least 19 weeks. Physicians using misoprostol must be skilled at mechanical dilation, since this is commonly required.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Buccal; Administration, Intravaginal; Adolescent; Adult; Cervix Uteri; Diarrhea; Dilatation; Early Termination of Clinical Trials; Female; Humans; Laminaria; Misoprostol; Patient Satisfaction; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Premedication; Self Administration; Single-Blind Method; South Africa; Vacuum Curettage; Young Adult

To compare the efficacy of Laminaria tents with Misoprostol for cervical ripening before surgical process in missed abortion.. In a prospective study, 70 women with missed abortion were assigned to have either insertion of a 3 mm intracervical Laminaria tent (n = 35) or vaginal Misoprostol 400 μg (n = 35) on the day prior to suction dilation and curettage (D/C). The women were interviewed just prior to the D/C with regard to pain, vaginal bleeding, and cervical dilator preference.. Cervical dilation was greater in the Laminaria group but not significantly different from that in the Misoprostol group. However, additional cervical dilation before D/C was required in more patients in the Misoprostol group (45.7 vs 14.3%, P = 0.001). Women who received Laminaria reported significantly more pain at the time of insertion (62.8% in Laminaria group vs 22.8% in Misoprostol group) compared with women who received Misoprostol. Conversely, Misoprostol was associated with more nausea, vomiting, diarrhea and vaginal bleeding.. Laminaria tents are more effective cervical dilators than vaginal Misoprostol when inserted the day prior to suction D and C. Vaginal Misoprostol insertion is more comfortable, although it is associated with an increased risk of vaginal bleeding.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Missed; Administration, Intravaginal; Adult; Cervical Ripening; Diarrhea; Dilatation and Curettage; Female; Humans; Labor Stage, First; Laminaria; Misoprostol; Nausea; Pain; Pregnancy; Uterine Hemorrhage; Vomiting; Young Adult

This randomized controlled trial compared the use of sublingual misoprostol with or without an additional 1 week course of sublingual misoprostol for the medical management of silent miscarriage.. A total of 180 women who had silent miscarriage (<13 weeks) was given 600 microg of misoprostol every 3 h for a maximum of three doses. These women were randomized into two groups: (i) no extended course of misoprostol or (ii) an extended course of sublingual misoprostol 400 microg daily for 1 week. The primary outcome measure was complete miscarriage rate.. The success rates for complete miscarriage were similar in both groups (group 1: 92.2%; 95% CI: 86.1-97.5% and group 2: 93.2%; 95% CI: 84.6-96.8%). There were no serious complications. The incidence of diarrhoea was higher (P < 0.01) in the group with an extended course of sublingual misoprostol. Other side-effects were similar.. Sublingual misoprostol is useful for the management of silent miscarriage. An additional 1 week course of sublingual misoprostol did not improve the success rate or shorten the duration of vaginal bleeding. Instead, it increased the incidence of diarrhoea.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Spontaneous; Administration, Sublingual; Diarrhea; Female; Hemorrhage; Humans; Misoprostol; Pregnancy; Pregnancy Trimester, First; Vagina

To compare three methods of labour induction.. Randomised controlled trial.. Academic hospitals in Johannesburg, South Africa.. Women with intact membranes due for induction of labour.. Randomised, sealed opaque envelopes were used to allocate women to labour induction with extra-amniotic Foley catheter/titrated oral misoprostol solution (N = 174), titrated oral misoprostol solution alone (N = 176), or vaginal dinoprostone (N = 176). Misoprostol was dissolved in water and 20-40 g was given 2-hourly.. These were failure to deliver vaginally within 24 hours, additional measures for induction or augmentation of labour, analgesia, and maternal and fetal complications.. In the Foley catheter group, misoprostol was required in all but 1 case. Failure to deliver vaginally within 24 hours was similar for the three groups (79/174 v. 70/176 v. 70/176 respectively). Labour augmentation, caesarean section and instrumental delivery were used somewhat more frequently in the Foley/misoprostol group than in the misoprostol alone group, but these differences were not statistically significant. More analgesia was used in the Foley catheter/misoprostol group than in the misoprostol group (64/172 v. 46/175). Side-effects and neonatal complications were similar for the three groups.. Use of extra-amniotic Foley catheter placement showed no measurable benefits over the use of oral misoprostol alone, or vaginal dinoprostone.

Topics: Administration, Intravaginal; Administration, Oral; Adult; Analgesia, Obstetrical; Catheterization; Combined Modality Therapy; Delivery, Obstetric; Diarrhea; Dinoprostone; Female; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Obstetric Labor Complications; Oxytocics; Pregnancy; Pregnancy Outcome; Titrimetry; Treatment Outcome

Prolonged vaginal bleeding is a common complaint after medical abortion. The effect of a 1 week course of daily oral misoprostol after medical abortion with mifepristone and misoprostol on the amount of post-abortal blood loss was studied.. A total of 150 women (gestation

Topics: Abortifacient Agents, Steroidal; Adult; Diarrhea; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Treatment Failure; Uterine Hemorrhage

To evaluate the side effects of 600 microg misoprostol orally during the first 24 hours after administration in the third stage of labour.. Double blind randomised controlled trial.. Tertiary care hospitals in Nigeria and Thailand.. All women participating in the WHO Misoprostol trial in these two hospitals between January 1, 1999 and June 17, 1999.. All women were followed up during the first 24 hours postpartum to evaluate the occurrence of shivering, nausea, vomiting, diarrhoea and other misoprostol-related side effects.. Rates of shivering, nausea, vomiting, diarrhoea and pyrexia within 1 hour and in the intervals 2-6, 7-12, 13-18 and 19-24 hours after delivery.. A total of 1686 women were enrolled. Women who received misoprostol had higher incidence than the oxytocin group of 'any' shivering in the first hour (RR 6.4, 95% CI 3.9 to 10.4) and the period covering 2-6 hours following delivery (RR 4.7, 95% CI 1.9 to 11.2). Pyrexia was also more common in the misoprostol group in both the same time intervals (RR 2.8, 95% CI 1.4 to 5.3 and RR 6.3, 95% CI 3.7 to 10.8, respectively). Diarrhoea was not present in the first hour in either group but appeared in the second time period (2-6 hours) and third time period (7-12 hours) more frequently in the misoprostol group than with oxytocin.. The increased incidence of shivering and pyrexia that occurs with postpartum use of misoprostol persists up to 6 hours following delivery. Approximately 5% of women experience diarrhoea that starts after 1 hour and subsides within 12 hours.

Topics: Administration, Oral; Diarrhea; Double-Blind Method; Female; Fever; Follow-Up Studies; Humans; Labor Stage, Third; Misoprostol; Oxytocics; Postpartum Hemorrhage; Pregnancy; Puerperal Disorders; Risk Factors; Shivering; Time Factors

To compare the incidence of selected spontaneously reported adverse events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX, 12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).. Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint: self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric discomfort, heartburn, nausea, vomiting).. Among 483 patients (80.3% females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively reported diarrhea 6.2% vs 16.2% (p<0.001); drug-related diarrhea 3.7% vs 16.2% (p<0.001); one or more clinical AEs 52.9% vs 73.0% (p<0.001); GI AEs 28.9% vs 48.5% (p<0.001); NSAID-type GI AEs 18.6% vs 29.9% (p=0.004); discontinuations due to abdominal pain 0.4% vs 3.7% (p<0.05); and discontinuations due to any AE 4.1% vs 9.1% (p=0.029). No significant differences were observed in efficacy.. Rofecoxib 12.5 mg qd has improved GI tolerability and similar efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).

Topics: Abdominal Pain; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Diarrhea; Diclofenac; Double-Blind Method; Drug Combinations; Female; Humans; Lactones; Male; Middle Aged; Misoprostol; Osteoarthritis; Severity of Illness Index; Sulfones; Treatment Outcome

The objective of this study was to evaluate the safety and efficacy of 1000 microg misoprostol vaginally (Cytotec) self-administered into the vagina for medical abortion. Three-hundred women with gestations between 42 and 63 days, with previous written consent, received vaginal misoprostol every 24 h up to a maximum of three doses for abortion. Outcome measures assessed included: successful abortion (complete abortion without surgery), side effects, decrease in hemoglobin, mean time of vaginal bleeding, mean expulsion time and mean time of returning of menses. Complete abortion occurred in 279/300 (93.0%, 95% CI 90, 96) patients. Medication to relieve symptoms was administered to all subjects after every misoprostol dose. Vaginal bleeding lasted 14.7 +/- 5.4 days. Mean expulsion time was 8.1 +/- 3.0 h for those who aborted after the first misoprostol dose. The mean drop in hemoglobin was statistically significant (p = 0.0001) but without clinical relevance. The frequencies of nausea and diarrhea were high. According to the observed outcomes, 1000-microg misoprostol vaginally could be a valid method to terminate pregnancies up to nine weeks gestation.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Adolescent; Adult; Diarrhea; Female; Gestational Age; Hemoglobins; Humans; Menstruation; Misoprostol; Nausea; Pregnancy; Self Administration; Time Factors; Uterine Hemorrhage

The objectives of this prospective non-concurrent cohort study were to confirm the efficacy of vaginal misoprostol for early pregnancy termination and to determine whether the incidence of side effects is lower with prophylactic loperamide and acetaminophen. Two-hundred women with an intrauterine pregnancy < or =56 days gestational age seeking medical pregnancy termination in an ambulatory research clinic were enrolled in the study. One-hundred participants (group 1) ingested 4 mg of loperamide and 500 mg of acetaminophen before the vaginal placement of 800 mirog of misoprostol moistened with 2 mL of saline. If abortion had not occurred, the same regimen was repeated every 24 h (maximum three doses). One-hundred participants (group 2) from the same clinic who previously underwent the same misoprostol regimen without prophylactic medication served as a control group for comparison with respect to abortion success and the incidence of side effects. The rate of successful abortion was not statistically significantly different between the two groups (group 1 93%, group 2 89%). The incidence of opiate analgesic use was significantly less in group 1 (4%) compared with group 2 (16%) (OR 0.22, 95% CI 0.06-0.73, p = 0.01). There was a significantly lower incidence of diarrhea in group 1 (23%) compared with group 2 (44%) (OR 0.38, 95% CI 0.20-0.73, p = 0.003). There was no difference in the incidence of fever/chills or the incidence of emesis between the two groups. Vaginal misoprostol is effective for termination of pregnancy < or = 56 days and the incidence of diarrhea and the use of opiate analgesia is significantly reduced with prophylactic loperamide and acetaminophen.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Acetaminophen; Administration, Intravaginal; Adolescent; Adult; Analgesics, Non-Narcotic; Antidiarrheals; Cohort Studies; Diarrhea; Female; Fever; Gestational Age; Humans; Loperamide; Middle Aged; Misoprostol; Patient Satisfaction; Pregnancy; Surveys and Questionnaires; Vomiting

A prospective randomized controlled trial was conducted to compare the efficacy and side-effects of vaginal versus oral misoprostol in the medical management of incomplete miscarriage.. Two hundred and one patients who miscarried consented to randomization using computer-generated randomization model prior to treatment. A total of 800 microg of misoprostol was given either vaginally or orally to the randomized subjects. A second dose was repeated 4 h later if the product of conception had not been passed.. The incidence of complete uterine evacuation following vaginal and oral misoprostol was similar [(58/95) 61.1% versus (67/103) 64.4%]. There was a significantly decreased incidence of diarrhoea [(12/95) 13.6% versus (62/103) 65.3%, P < 0.01] with the use of vaginal misoprostol.. Vaginal misoprostol was as effective as oral misoprostol in medical uterine evacuation in patients with incomplete miscarriage. There was also a reduction in the incidence of diarrhoea with the use of vaginal misoprostol.

Topics: Abortion, Incomplete; Administration, Intravaginal; Administration, Oral; Adult; Diarrhea; Female; Humans; Misoprostol; Pelvic Pain; Pregnancy

The objective of this study was to compare the oral and vaginal administration of misoprostol for cervical priming before surgical abortion up to 63 days' gestation. A total of 900 pregnant women, with ages ranging from 18 to 42 years, who asked for pregnancy termination, were included in this study. Women were randomly allocated to one of the following groups: oral administration of 400 microg misoprostol, 8 h before aspiration; and vaginal self-administration of 400 microg misoprostol, 4 h before aspiration. During admission, all subjects were checked on a 15-min basis. The preoperative cervical dilatation achieved was the main outcome assessed. The cervix was dilated (Hegar > or = 8) in 348 (78%) subjects from the oral treatment group and in 391 (87%) women from the vaginal treatment group; this difference was statistically significant (p = 0.0004). The mean dilatation achieved in the oral treatment group was 8.1 mm (SD 1.6 mm) and it was 8.5 mm (SD 1.5 mm) in the vaginal treatment group; this difference was statistically significant (p = 0.0001). The frequencies of side-effects such as nausea, vomiting, diarrhea and chills reported by women from the vaginal misoprostol group were 10, 8, 18 and 4 times lower, respectively, than those reported by subjects from the oral misoprostol group. In conclusion, vaginal self-administration of misoprostol was the best administration route, as it obtained the same or greater priming effectiveness of the cervix in half the time with a much lower frequency of side-effects.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Administration, Oral; Adolescent; Adult; Analysis of Variance; Chills; Diarrhea; Female; Humans; Misoprostol; Nausea; Pregnancy; Pregnancy Trimester, First

It is known that when misoprostol is given at 200 microg every 3 h after mifepristone pretreatment, the vaginal route is more effective than the oral route. However, women prefer the oral route. This randomized study was to test our hypothesis that oral misoprostol 400 microg is as effective as vaginal misoprostol 200 microg when given every 3 h in termination of second trimester pregnancy after priming with mifepristone. A total of 142 patients was randomly assigned to group 1 (200 mg mifepristone + 400 microg oral misoprostol every 3 h up to five doses) or group 2 (200 mg mifepristone + 200 microg vaginal misoprostol every 3 h up to five doses). The incidence of side-effects and the preference study were assessed through a standardized questionnaire during and after the abortion. For the oral group, both the incidence of diarrhoea (40.0 versus 23.2%, P = 0.03) and the amount of drug used (1734 compared with 812 microg, P < 0.0001) were significantly higher than that of the vaginal group but the incidence of fever appeared to be lower (not significant). There was no significant difference in complete abortion rate: 81.4% in the oral group and 75.4% in the vaginal group. The median induction-abortion interval was similar in the two groups (10.4 versus 10.0 h). The percentage of women who aborted in 24 h was also similar: 57/70 (81.4%) in the oral group and 58/69 (87.0%) in the vaginal group. Overall, 82.0% of women preferred the oral route. Oral misoprostol (400 microg) given every 3 h up to five doses, when combined with mifepristone, was as effective as the vaginal (200 microg) route in second trimester termination of pregnancy. This regimen could also be offered to those women who found repeated vaginal administration unacceptable.

Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Administration, Intravaginal; Administration, Oral; Adolescent; Adult; Diarrhea; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, Second

A study was undertaken to determine whether the combination of oral tamoxifen and moistened misoprostol administered vaginally was superior to that of placebo and moistened misoprostol administered vaginally for elective termination of early pregnancies.A clinical trial was conducted with a study group of 150 healthy women with pregnancies of

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Diarrhea; Double-Blind Method; Estrogen Antagonists; Female; Hemoglobins; Humans; Misoprostol; Patient Satisfaction; Pelvic Pain; Pregnancy; Prospective Studies; Tamoxifen; Ultrasonography, Prenatal; Uterine Hemorrhage; Vomiting

A prospective randomized trial was conducted in 140 women to compare the efficacy of vaginal gemeprost with vaginal misoprostol for termination of second trimester pregnancy. Women requesting termination of second trimester pregnancy were randomized into two groups. Group A women were given 1 mg vaginal gemeprost every 3 h for a maximum of five doses in the first 24 h, whereas group B women were given 400 micrograms vaginal misoprostol every 3 h for a maximum of five doses in 24 h. The median induction-abortion interval in the vaginal misoprostol group (14.1 h) was significantly shorter than that in the gemeprost group (19.5 h). The percentage of women who achieved successful abortion within 24 h in the misoprostol group (80.0%) was significantly higher than that in the gemeprost group (58.6%). There was no significant difference in the incidence of side effects between the two groups except for diarrhea, which was more common in the gemeprost group. The incidence of fever was more common in the misoprostol group. It is concluded that vaginal misoprostol is more effective than gemeprost in termination of second trimester pregnancy.. The efficacies of vaginal gemeprost and vaginal misoprostol for the termination of second-trimester pregnancies were compared in a prospective, randomized trial conducted in Hong Kong, China. 140 women 16-40 years of age requesting pregnancy termination at gestational ages of 14-20 weeks were allocated to receive either 1 mg of gemeprost every 3 hours up to 5 doses (n = 70) or 400 mcg of misoprostol every 3 hours up to 5 doses (n = 70). 56 women (80.0%) in the misoprostol group and 41 (58.6%) in the gemeprost group aborted within 24 hours. In primigravidas, the rate of successful abortion was significantly higher in the misoprostol group (83.3%) than the gemeprost group (55.3%). There were no significant between-group differences in this rate for multigravid women. The median induction-abortion interval was significantly shorter in the misoprostol group (14.1 hours) than the gemeprost group (19.5 hours). Blood loss during the procedure was similar in both groups. Although there was no significant difference in the incidence of side effects, diarrhea was less common in misoprostol acceptors (24.3%) than in women who received gemeprost (40.0%). In addition to being more effective at inducing abortion, misoprostol is substantially less expensive than gemeprost and does not require refrigerated transport and storage facilities. Thus, misoprostol, with or without mifepristone, should be the drug of choice for termination of mid-trimester pregnancies. Further studies are needed, however, to determine the optimal dose and frequency of administration.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Adolescent; Adult; Alprostadil; Diarrhea; Female; Fever; Humans; Misoprostol; Pregnancy; Pregnancy Trimester, Second

To determine whether misoprostol (a prostaglandin E1 analogue) 400 micrograms orally (group 1) or 800 micrograms vaginally (group 2) will cause complete uterine evacuation in women with early pregnancy failure.. Twenty subjects were recruited for a prospective, non-blinded, randomized clinical trial. Early pregnancy failure was diagnosed by transvaginal ultrasound examination; only women with a closed cervical os and minimal vaginal bleeding were enrolled. Subjects returned 24 hours after misoprostol administration for a transvaginal ultrasound examination. If the gestational sac was still present, the misoprostol dose was repeated and the subject returned again 24 hours later. Subjects who failed to expel the pregnancy were offered a suction curettage.. Twelve and eight women were randomized to groups 1 and 2, respectively. Complete uterine evacuation occurred in three of 12 [25%, 95% confidence interval (CI) 1%, 50%] and seven of eight (88%, 95% CI 65%, 100%, P = .010) subjects in groups 1 and 2, respectively. Vomiting occurred in 30% and 13%, respectively, and diarrhea in 50% and 38%, respectively.. Vaginal misoprostol 800 micrograms is more effective than oral misoprostol 400 micrograms for uterine evacuation of early pregnancy failure and may be an effective alternative to dilation and curettage.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Missed; Administration, Intravaginal; Administration, Oral; Adult; Diarrhea; Female; Humans; Misoprostol; Pilot Projects; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Ultrasonography; Vomiting

To compare the abortifacient efficacies of two intravaginally administered misoprostol doses and gemeprost in termination of second-trimester pregnancy.. Eighty-one women between 12 and 24 weeks' gestation requesting abortion were randomized to receive intravaginally either 100 micrograms of misoprostol at 6-hour intervals (n = 27), 200 micrograms of misoprostol at 12-hour intervals (n = 26), or 1.0 mg of gemeprost at 3-hour intervals (n = 28). The regimen was continued until abortion, or for 36 hours, with assessment of the rate of complete and incomplete abortions as well as side effects within 48 hours from the start of the treatment.. The final rates of terminations were 74% in the 100-microgram misoprostol group, 92% in the 200-microgram misoprostol group, and 89% in the gemeprost group. Abortion was complete in 37%, 61%, and 32% in each group, respectively (P = .03, when the 200-microgram misoprostol group was compared with the two other groups). The induction-to-abortion interval was longer (P = .001) in the misoprostol groups (mean 23.1 hours for the 100-microgram and 27.8 hours for the 200-microgram dose) than in the gemeprost group (14.5 hours). There was less pain (P = .01), diarrhea (P = .001), and vomiting (P = .01) in the misoprostol groups than in the gemeprost group. The mean blood loss in the misoprostol groups was lower than in the gemeprost group (P = .001).. Intravaginal application of 200 micrograms of misoprostol at 12-hour intervals in induction of second-trimester abortion is equally effective to a standard gemeprost regimen. Misoprostol causes fewer side effects and is cheaper and more practical to use.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Adult; Alprostadil; Diarrhea; Drug Administration Schedule; Female; Humans; Misoprostol; Nausea; Pain; Pregnancy; Pregnancy Trimester, Second; Time Factors

To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs).. 6-month randomized, double-blind, placebo-controlled trial.. 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada.. 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993.. Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day.. Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy).. Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P < 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months.. In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diarrhea; Double-Blind Method; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Misoprostol; Odds Ratio; Risk Factors

Medical termination of pregnancy can be successfully performed with a combination of mifepristone (RU 486) and a prostaglandin analogue. We conducted a prospective, randomized trial to compare oral with vaginal administration of the prostaglandin E1 analogue misoprostol for first-trimester abortion in women treated initially with mifepristone.. The study population consisted of 270 women seeking abortion within 63 days after the onset of amenorrhea. The dose of mifepristone was 600 mg, and the dose of misoprostol was 800 micrograms. The study had two primary end points: expulsion of the conceptus without the need for a surgical procedure, and abortion within four hours after the administration of misoprostol.. Expulsion of the conceptus without the need for a surgical procedure occurred in 95 percent of the women who received misoprostol vaginally and in 87 percent of those who received it orally (P = 0.03). The rate of continued pregnancy was 7 percent with the oral regimen and 1 percent with the vaginal regimen (P = 0.01). Ninety-three percent of the women receiving misoprostol vaginally had abortions within four hours, as compared with only 78 percent of the women receiving the drug orally (P < 0.001). Vomiting and diarrhea were reported more frequently by the women who received oral misoprostol than by those who received vaginal misoprostol (P = 0.04 and P = 0.002, respectively).. After the administration of mifepristone, vaginal administration of misoprostol is more effective and better tolerated than oral administration for the induction of first-trimester abortion.. During June 1993-January 1994 in Scotland, clinicians recorded data on 270 women attending the fertility control clinic at Aberdeen Royal Hospitals for voluntary termination of early pregnancy (within 63 days from onset of amenorrhea). They received 600 mg of oral RU-486 on day 1 and either 800 mcg of oral misoprostol or 800 mcg misoprostol inserted deep into the vagina 36-48 hours later. Researchers wanted to compare the safety and efficacy of 800 mcg oral misoprostol with the safety and efficacy of 800 mcg vaginal misoprostol in women who had previously received RU-486. 2.6% aborted before receiving misoprostol. Complete abortion without surgical intervention was more frequent in the vaginal misoprostol group than the oral misoprostol group (95% vs. 87%; p = 0.03). The continued pregnancy rate was lower in the vaginal misoprostol group than the oral misoprostol group (1% vs. 7%; p = 0.01). Expulsion of the conceptus was more likely to occur within 4 hours of receiving misoprostol among the vaginal group than the oral group (93% vs. 78%; p 0.001). The oral misoprostol group had a higher incidence than the vaginal misoprostol group of vomiting (44% vs. 31%; p = 0.04) and diarrhea (36% vs. 18%; p = 0.002). The two groups did not differ significantly with respect to other side effects or severity of symptoms. The women in the oral misoprostol group were more likely to think that the antiemetic drug took minutes rather than 1 or more hours to act than those in the vaginal misoprostol group (61% vs. 34%; p 0.001). These findings show that, following administration of RU-486, vaginal misoprostol was better tolerated and more effective than oral misoprostol at inducing abortion in women in the first trimester of pregnancy.

Topics: Abortion, Induced; Administration, Intravaginal; Administration, Oral; Adult; Confidence Intervals; Diarrhea; Female; Follow-Up Studies; Humans; Mifepristone; Misoprostol; Pregnancy; Prospective Studies; Vomiting

A multicentre randomized open clinical trial was conducted to compare the efficacy and side effects of two regimens of mifepristone with misoprostol, and mifepristone with PG05 for termination of early pregnancy (amenorrhoea < = 49 days). Six-hundred women in early pregnancy, who requested medical abortion were randomly allocated into 3 groups. In group 1 (n = 301), an initial dose of mifepristone 50 mg was given, followed by 25 mg every 12 hours up to a total dose of 150 mg mifepristone, plus a single oral dose of misoprostol 600 micrograms in the morning of the third day. In group 2 (n = 150), the same regimen of mifepristone was given, but dl-15-methyl PGF2 alpha (PG05) 1 mg vaginal suppository was inserted on the third day. In group 3 (n = 149), a single dose of mifepristone 200 mg was given and misoprostol 600 micrograms was used as in group 1. The complete abortion rate were 94.4%, 97.3%, and 94.6% for group 1, 2 and 3, respectively. 3.0, 2.0 and 2.7% of women had incomplete abortion, and 1.7, 0.7 and 2.0% of women in the 3 groups were treatment failures; in the remaining 1% in group 1 and 0.7% in group 3, treatment outcome could not be determined. There were no significant differences among the 3 groups. Lower abdominal pain was the main complaint which was reported by 82% of the subjects after PGs administration. The incidence of diarrhoea in PG05 group (38.7%) was significantly higher than that in the other two groups (21.6 and 20.1%) (P < 0.001), and so was vomiting. It was concluded that misoprostol, as an orally effective prostaglandin, in combination with mifepristone for induced abortion of early pregnancy was as effective as PG05 vaginal suppository. Besides, it has advantages of convenience of use, less side effects, easy storage and transfer, and low cost.

Topics: Abdominal Pain; Abortion, Induced; Administration, Oral; Adolescent; Adult; China; Diarrhea; Dinoprost; Dose-Response Relationship, Drug; Female; Humans; Mifepristone; Misoprostol; Pessaries; Pregnancy; Pregnancy Trimester, First; Uterine Hemorrhage

A randomized, double-blind, controlled study was performed with 18 arthritic dogs administered aspirin (25 mg/kg of body weight, PO, q 8 h) and excipient (control group) or aspirin and misoprostol (100 micrograms, PO, q 8 h). Dogs in the misoprostol (n = 10) and control (n = 8) groups were primarily compared by use of sequential gastroduodenoscopy, changes in PCV, and prevalence of clinical signs of gastrointestinal disturbance over a 14-day treatment period. The misoprostol/aspirin-treated group had significantly (P < 0.05) less gastroduodenal hemorrhage and ulceration and a significantly (P < 0.05) lower prevalence of vomiting than did the control group.

Topics: Animals; Aspirin; Diarrhea; Dog Diseases; Dogs; Double-Blind Method; Duodenoscopy; Female; Gastrointestinal Hemorrhage; Gastroscopy; Male; Misoprostol; Osteoarthritis; Peptic Ulcer; Vomiting

Data from four double-blind studies of the treatment of patients with rheumatoid arthritis or osteoarthritis were combined. For 4 to 12 weeks, 747 patients received Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol, and 754 patients received 50 mg of diclofenac; the drugs were given twice or three times daily. The five most commonly reported adverse events were abdominal pain by 23.2% of the diclofenac/misoprostol patients and 19.8% of the diclofenac patients; diarrhea by 19.9% and 11.3%; nausea by 11.8% and 6.5%; dyspepsia by 11.2% and 7.8%; and flatulence by 8.0% and 3.1%. Other adverse events, reported by similar proportions of both treatment groups, included headache, gastritis, dizziness, vomiting, and constipation. In the diclofenac/misoprostol-treated patients, the abdominal pain and diarrhea were rated mild in 30.6% and 24.3%, moderate in 49.1% and 51.4%, and severe in 20.2% and 24.3%. Serious adverse events occurred in eight of the diclofenac/misoprostol-treated patients and in 13 of the diclofenac-treated patients; 12.6% and 10.1%, respectively, were withdrawn from the study because of adverse events. Results of laboratory tests of hepatic and renal function were similar in the two treatment groups.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Constipation; Diarrhea; Diclofenac; Dizziness; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Misoprostol; Osteoarthritis; Pain; Vomiting

Ninety-one normal, healthy volunteers participated in a single-center, double-blind, placebo-controlled, randomized, parallel group study: 1) to compare the prostaglandin E1 analog, misoprostol, given at a dose of 200 micrograms bid, with the recommended dose of 200 micrograms qid in protecting the gastroduodenal mucosa against injury due to anti-inflammatory doses of aspirin (3900 mg/day); and 2) to determine whether the reduced dose was associated with a lesser incidence of gastrointestinal (GI) side effects, particularly diarrhea. All subjects received 975 mg of aspirin qid with meals and at bedtime. They were concurrently administered either misoprostol 200 micrograms qid, misoprostol 200 micrograms bid and placebo bid, or placebo qid. All subjects were endoscopically normal at the onset of the study and were re-endoscoped on the morning of the 7th day of therapy, 2 h after the morning dose of medications. Gastric and duodenal mucosa were assessed separately on a 0-7 scale which gave a greater weight to erosions than to hemorrhages. GI symptoms, especially bowel habits, were assessed by means of diary cards. Subjects in both misoprostol groups had significantly less gastric and duodenal mucosal injury than subjects who received placebo (p less than 0.007 for each pairwise comparison). There was no statistically significant difference between the two misoprostol groups (p less than 0.093). Subjects in the misoprostol 200 micrograms qid group had significantly more loose and watery bowel movements than the subjects in the misoprostol 200 micrograms bid group (p less than 0.013), whereas there were no significant differences in bowel habits between the misoprostol 200 micrograms bid and placebo groups (p less than 0.122). More subjects in the misoprostol 200 micrograms qid group reported abdominal pain, loose stools, watery stools, flatulence, dyspepsia, and nausea than in the misoprostol 200 micrograms bid and placebo groups. In conclusion, the adverse events in the misoprostol 200 micrograms bid group were not significantly different from those in the placebo group, and were significantly better than in the misoprostol 200 micrograms qid group. The lower dose retained mucosal protective activity that was statistically indistinguishable from that of misoprostol 200 micrograms qid.

Topics: Adult; Aspirin; Diarrhea; Double-Blind Method; Duodenal Diseases; Duodenoscopy; Female; Gastric Mucosa; Gastroscopy; Humans; Intestinal Mucosa; Male; Middle Aged; Misoprostol; Stomach Diseases

This study was undertaken to evaluate the safety and therapeutic efficacy of the prostaglandin E1 analogue, misoprostol, when compared with ranitidine in the healing of duodenal ulcers. Sixty patients with endoscopically proven duodenal ulcers participated in a double-blind controlled randomised trial comparing misoprostol 400 microgram and ranitidine 150 mg, both given twice daily orally for up to 8 weeks. Patient characteristics at entry into the trial were similar in the two treatment groups, except that there were 6 women in the ranitidine-treated group and none in the misoprostol-treated group. Ulcers were 0.3 - 2.0 cm in length. Healing was determined by endoscopy at 4 weeks; if ulcers were not healed, endoscopy was repeated at 8 weeks. All patients were given antacid tablets to be used as needed for pain up to a maximum of 8 tablets per day. Healing rates at 4 weeks for a total of 58 evaluate patients in the two treatment groups were: misoprostol (15/29; 51.7%) and ranitidine (20/29; 69.0%). Healing rates at 8 weeks for a total of 55 evaluable patients in the two treatment groups were: misoprostol (21/27; 77.8%) and ranitidine (24/28; 85.7%). The healing rate for misoprostol did not differ significantly from that for ranitidine at both the 4-week (P = 0.28) and the 8-week assessment (P = 0.68). Diarrhoea was the most common side-effect but was usually mild. It occurred in 11 patients on misoprostol and 1 patient on ranitidine. These results indicate that misoprostol 400 micrograms was taken twice daily orally for up to 8 weeks is effective and safe for the treatment of duodenal ulcer.

Topics: Adult; Alprostadil; Anti-Ulcer Agents; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Misoprostol; Random Allocation; Ranitidine; Smoking; Time Factors

Misoprostol is an E1 prostaglandin analog. Most of the other synthetic prostaglandins that are being studied in advanced clinical trials for gastrointestinal diseases are E2 derivatives. Misoprostol has shown a dose-related antisecretory effect that lasted 3-5.5 hr. In addition, animal studies have shown cytoprotective properties that are being confirmed in clinical studies. Ulcer-healing trials using four times daily dosing appear to parallel the antisecretory dose-response curve up to a dose of 200 micrograms qid. Evidence presented in this supplement suggests a further increase in healing-rate response at 300 micrograms misoprostol qid. The misoprostol healing rates obtained in duodenal ulcer and gastric ulcer therapy at 200 micrograms qid are not significantly different from those seen in the same studies with cimetidine at a dose of 300 mg qid. No significant rebound in recurrence has been observed during follow-up for 12 months after short-term 100- and 200-micrograms qid misoprostol treatment. The most frequent adverse effects are dose-related diarrhea and abdominal cramping, which are transient in most patients and have not caused a significant problem in clinical use. There is also a tropic effect on the pregnant uterus, which was observed in a special pharmacologic clinical study. No significant abnormalities have been detected in clinical laboratory tests or gastric biopsies. There have also been no adverse effects noted on blood pressure, pulse, platelets, the immune system, pulmonary function, gastrointestinal hormones, or the endocrine system. These previously discussed characteristics of misoprostol, and current data, suggest that this prostaglandin E1 derivative may be an important addition to the treatment of peptic ulcer disease.

Topics: Alprostadil; Anti-Ulcer Agents; Cimetidine; Clinical Trials as Topic; Diarrhea; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Humans; Immune System; Misoprostol; Peptic Ulcer; Platelet Aggregation; Recurrence; Uterus

This study was undertaken to evaluate the efficacy of misoprostol taken twice daily for the healing of duodenal ulcer. Three hundred thirty patients with endoscopically proven duodenal ulcer participated in a multicenter, double-blind, controlled trial comparing placebo with misoprostol 200 micrograms and 400 micrograms twice daily for up to four weeks. Patient characteristics were similar in all three treatment groups. Ulcers were between 0.3 cm and 2.0 cm in length. Healing was determined by endoscopy at two weeks; if ulcers were not healed, endoscopy was repeated at four weeks. All patients were given Al(OH)3 antacid (up to 54 meq a day) to be used as needed for pain. Healing rates at four weeks for a total of 280 evaluable patients in the three treatment groups were as follows: misoprostol 400 micrograms bid, 65.4%; misoprostol 200 micrograms bid, 52.9%; and placebo, 42.2%. Misoprostol 400 micrograms bid was superior to placebo (P = 0.002) in healing ulcers. However, the healing rate for misoprostol 200 micrograms bid did not differ significantly from placebo. The percentage of nonsmokers who healed at four weeks was higher than that of smokers in both misoprostol-treatment groups, although the difference was not analyzed for statistical significance. There were no differences in antacid consumption or pain relief among the three experimental groups during the study. Diarrhea was the most common side effect but was mild and self-limiting, occurring in 8.9%, 5.9%, and 1.8% of the misoprostol 400 micrograms, 200 micrograms, and placebo groups, respectively. These results indicate that misoprostol 400 micrograms taken twice daily for four weeks is effective and safe for the treatment of duodenal ulcers.

Topics: Adult; Aged; Alprostadil; Anti-Ulcer Agents; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Duodenal Ulcer; Humans; Middle Aged; Misoprostol; Prostaglandins; Smoking; Wound Healing

Patients with endoscopically documented duodenal ulcer participated in a double-blind, multicenter trial comparing placebo with misoprostol 100 micrograms administered q.i.d. for up to four weeks in the treatment of duodenal ulcer. Ulcers were examined endoscopically at two weeks and, if not healed, again at four weeks. Acetaminophen was permitted for pain relief. At four weeks, of 286 patients admitted to the study, the cumulative healing rate for the 227 evaluable patients was 64.9% for misoprostol and 47.4% for placebo (P = 0.008). Misoprostol was also significantly superior to placebo in promoting ulcer healing when all patients entering the study (intent-to-treat cohort) were compared (P = 0.018), and in a modified intent-to-treat cohort consisting of all patients whose final endoscopic results were known (P = 0.005). Ulcer symptoms were similar in both treatment groups, and most patients in both groups were pain free at the end of the first two weeks of treatment. Diarrhea was the most frequently reported adverse experience (8.5% for misoprostol and 3.5% for placebo). This symptom was mild and self-limiting in spite of continued use of misoprostol. We conclude that misoprostol 100 micrograms q.i.d. for four weeks is safe and effective in the healing of duodenal ulcers.

Topics: Adult; Aged; Alprostadil; Anti-Ulcer Agents; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Duodenal Ulcer; Duodenoscopy; Female; Headache; Humans; Male; Middle Aged; Misoprostol; Pain; Placebos; Random Allocation

Misoprostol, a synthetic analog of prostaglandin E1, inhibits gastric acid production and is cytoprotective at doses well tolerated by patients in preliminary trials. This multicenter double-blind study was performed in out-patients with endoscopically demonstrated duodenal ulcers, to compare the efficacy in ulcer healing and the safety of two dosages of misoprostol and placebo. Up to six antacid tablets daily were permitted for pain. 308 patients enrolled and were randomized to three treatment groups: placebo, misoprostol 50 micrograms and misoprostol 200 micrograms. After two weeks of treatment, the three groups had similar percentages of patients with complete ulcer healing. However, after four weeks, 76.6% of patients taking misoprostol 200 micrograms q.i.d. had complete healing, compared with 42.6% on misoprostol 50 micrograms q.i.d. and 51% on placebo (P less than 0.001, 200 micrograms versus placebo). Patients taking misoprostol 200 micrograms used less antacid than the others. Diarrhea, mild and self-limiting, was present in 13% of the 200 micrograms group versus 5% on placebo. We conclude that misoprostol 200 micrograms q.i.d. is effective, safe and well tolerated in the treatment of duodenal ulcers.

Topics: Adolescent; Adult; Aged; Alcohol Drinking; Alprostadil; Antacids; Anti-Ulcer Agents; Clinical Trials as Topic; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Duodenal Ulcer; Duodenoscopy; Female; Gastric Mucosa; Humans; Male; Middle Aged; Misoprostol; Pain; Random Allocation; Smoking

The number of subjects who had participated in completed clinical trials of misoprostol as of 1 May 1984 was 2272. Of this number 1549 subjects were exposed to misoprostol doses as high as 400 micrograms q.i.d. and for periods up to eight weeks. In ongoing trials subjects are receiving as much as 300 micrograms q.i.d. for up to 12 weeks, or 400 micrograms daily for up to one year. Five large controlled multicenter multicountry clinical trials have been conducted with misoprostol, including double-blind placebo-controlled comparisons of misoprostol in two duodenal ulcer studies and one gastric ulcer study, and double-blind comparisons of two doses of misoprostol and cimetidine in duodenal ulcer and gastric ulcer studies. In the placebo-controlled trials the only complaint clearly associated with misoprostol therapy in a meaningful number of patients was diarrhea, defined as any change in bowel habits whether or not this included true watery diarrhea. The incidence of diarrhea was higher with misoprostol 200 micrograms (13.1% of 107 subjects) and misoprostol 100 micrograms (9.5% of 199 subjects) than with placebo (3.8% of 314 subjects). This relatively high incidence of diarrhea is offset by the fact that only four subjects had withdrawn from studies worldwide because of diarrhea. It appears that compliance was excellent. In the cimetidine-controlled studies, diarrhea and related complaints were greater with misoprostol 200 micrograms (5.6% of 337 subjects) than with misoprostol 50 micrograms (3.0% of 328 subjects) or with cimetidine 300 micrograms q.i.d. (1.8% of 327 subjects).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alprostadil; Anti-Ulcer Agents; Biopsy; Cimetidine; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Gastric Mucosa; Gastrointestinal Diseases; Humans; Iron; Liver Function Tests; Misoprostol; Peptic Ulcer; Placebos; Pyloric Antrum; Recurrence

Research on medical abortion has been conducted in Hong Kong since the 1990s. It was not until 2011 that the first-trimester medical abortion service was launched. Mifepristone was registered in Hong Kong in April 2014 and all institutions that are listed in the Gazette as a provider for legal abortion can purchase mifepristone from the local provider. This article aimed to share our 3-year experience of this service with the local medical community. Our current protocol is safe and effective, and advocates 200-mg mifepristone and 400-µg sublingual misoprostol 24 to 48 hours later, followed by a second dose of 400-µg sublingual misoprostol 4 hours later if the patient does not respond. The complete abortion rate is 97.0% and ongoing pregnancy rate is 0.4%. Some minor side-effects have been reported and include diarrhoea, fever, abdominal pain, and allergy. There have been no serious adverse events such as heavy bleeding requiring transfusion, anaphylactic reaction, septicaemia, or death.

Topics: Abdominal Pain; Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Adolescent; Adult; Clinical Protocols; Diarrhea; Drug Hypersensitivity; Female; Fever; Hong Kong; Humans; Middle Aged; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First; Treatment Failure; Young Adult

Therapeutic interruption of the pregnancies of the 2nd and 3-rd quarter is often badly accepted by the patients and it is original that his realization is easy, effective and the less traumatic possible. In this indication, the sulprostone (Nalador) is a big contribution.. The purpose of our study is to review this product, to describe our experience concerning its use in the therapeutic interruptions of pregnancies and to study alternatives in case of failure or of against indication in its use.. It is about a forward-looking study opened from the 01-07-02 led in the service "A" of the CMNT. We brought together 30 women where a therapeutic interruption of the pregnancy was put and who did'nt present of against indications to the sulprostone.. The average age was of 27 years with extremes from 18 to 39 years 50% of our patients were nullipares. The terms of pregnancy varied from 16 to 28 LIMITED COMPANIES with an average of 20 LIMITED COMPANIES. The indications of these terminations of pregnancy were maternal in 33.33% of cases and foetal in 66.66% of cases. The average number of light bulbs of Nalador used by the women was of 2.25 with extremes going from 1 to 4. The delay of eviction from the beginning of the induction was on average of 21 hours, with a rate of success of 90%. We did not regret any break uterine Delivery was incomplete requiring a uterine revision under general anesthetic in 5 cases. Tolerance was good in general In case of failure alternatives were: the misoprostol (cytotec *), the Probe extra amniotic dries and the wet Probe.. The sulprostone by intravenous way constitutes an effective method of medical interruption of the pregnancy in the 2-nd and 3-rd quarter with a satisfactory tolerance and a rate of success of 90 %.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Therapeutic; Adolescent; Adult; Congenital Abnormalities; Diarrhea; Dinoprostone; Female; Fetal Death; Gestational Age; Humans; Misoprostol; Parity; Pelvic Pain; Pregnancy; Prospective Studies; Time Factors; Treatment Outcome; Vomiting

To assess the effectiveness of intravaginal misoprostol for second trimester uterine evacuation, we studied 70 women with singleton pregnancies complicated by fetal malformation or dead fetuses. Participants received 200 microg misoprostol administered at 4-hour intervals. Gestations with dead fetuses had a shorter induction-abortion interval [14.2 hours, standard deviation (SD) 4.3] than those with live, malformed fetuses (20.2 hours, SD 7.3) (P< 0.001). The abortion rate was significantly higher for gestations with dead fetuses (92.1%) than those with live, malformed fetuses (68.8%) (P< 0.05). There were no major complications and no significant difference in the incidence of side-effects. All women aborted within 38 hours. Administration of misoprostol is an effective clinical method to terminate second trimester, complicated pregnancy.

Topics: Abdominal Pain; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Congenital Abnormalities; Diarrhea; Drug Administration Schedule; Female; Fetal Death; Fever; Gestational Age; Hospitals, Military; Humans; Jordan; Misoprostol; Nausea; Parity; Postpartum Hemorrhage; Pregnancy; Pregnancy Trimester, Second; Time Factors; Treatment Outcome; Ultrasonography, Prenatal; Vomiting

Misoprostol is a synthetic prostaglandin E1 used during the first trimester of pregnancy as an adjacent to RU486 for medical termination of pregnancy. We present a case of a healthy 23-year-old woman who was admitted due to misoprostol overdose, used to induce an illegal abortion. Manifestations of toxicity included abdominal pain, vomiting, diarrhea and confusion. Treatment was supportive and included gastric lavage and administration of activated charcoal. Recovery was completed within a few hours, and the patient was scheduled for a dilatation and curettage the following day.

Topics: Abdominal Pain; Abortifacient Agents, Nonsteroidal; Abortion, Criminal; Adult; Diarrhea; Drug Overdose; Female; Gastric Lavage; Gestational Age; Humans; Misoprostol; Poisoning; Pregnancy; Vomiting

Misoprostol is a prostaglandin E(1) analogue that has been used for medical abortion. We conducted this prospective study to compare the efficacy of vaginal misoprostol for abortion in women at a gestational age of <42 days and in women at a gestational age of 42-56 days.. A total of 160 women seeking medical termination of a pregnancy of <56 days were enrolled in the study. Medical termination was performed using 800 micro g of vaginal misoprostol, repeated every 24 h for a maximum of three doses.. The overall complete abortion rate was 91.3%. In group A (gestation <42 days) complete abortion occurred in 96.3% of women, whereas in group B (gestation = 42-56 days) complete abortion occurred in 86.3% of women (P < 0.025). The two groups did not differ significantly with respect to side-effects (incidence of pain, bleeding, nausea, diarrhoea, fever and headache). Women who had aborted successfully were significantly more satisfied with the method compared with women who did not (P < 0.001).. The vaginal misoprostol-alone regimen is highly effective for women seeking medical abortion of pregnancies of

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Adolescent; Adult; Diarrhea; Female; Fever; Gestational Age; Headache; Humans; Misoprostol; Nausea; Pain; Patient Satisfaction; Pregnancy; Treatment Outcome; Uterine Hemorrhage

To evaluate the efficacy of a regimen of vaginal misoprostol in causing the complete expulsion of first-trimester missed abortions, or alternatively dilating the cervix for surgical evacuation.. Seventy-four women with a transvaginal ultrasound diagnosis of a first-trimester missed abortion and no more than slight vaginal bleeding were consecutively enrolled. Misoprostol (600 microg) was administered vaginally and repeated 4 h later if necessary. Surgical evacuation was performed when complete expulsion was not documented on the ultrasound 10-12 h after treatment.. Complete medical evacuation occurred in 42 women (56.8%), 11 (14.9%) of which required only one dose. Seventy women (94.6%) experienced abdominal pain, 73 (98.6%) vaginal bleeding, 10 (13.5%) nausea, 4 (5.4%) vomiting, 5 (6.8%) diarrhea, and 4 (5.4%) transient hyperthermia. There was one case of heavy vaginal bleeding requiring emergency surgical evacuation, and one re-admission for incomplete abortion at 30 days. All but 4 (5.4%) women had permeable cervices at the time of surgery.. The described regimen of vaginal misoprostol is safe and reasonably effective in inducing complete evacuation in missed abortions. When this does not occur, it almost always provides adequate cervical dilatation for surgery.

Topics: Abdominal Pain; Abortifacient Agents, Nonsteroidal; Abortion, Missed; Administration, Intravaginal; Adolescent; Adult; Diarrhea; Drug Administration Schedule; Female; Fever; Humans; Misoprostol; Nausea; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Time Factors; Ultrasonography; Uterine Hemorrhage; Vomiting

Twenty women who requested early first trimester termination of pregnancy were recruited to study the tolerability of a 2-week course of oral misoprostol after termination of pregnancy by mifepristone and vaginal misoprostol. Ten patients (50%) complained of mild diarrhea during the 2-week course of misoprostol. Otherwise, there were no other significant side effects. The 2-week course of misoprostol was well tolerated by women who underwent early first trimester termination of pregnancy with mifepristone and misoprostol.. A pilot study was conducted to assess whether prolonged use of misoprostol is well tolerated by women who have undergone termination of an early pregnancy with mifepristone and misoprostol and if this regimen increases the complete abortion rate and decreases the duration of bleeding. Enrolled were 20 women from Hong Kong and Shanghai with a menstrual delay of 21 days or less; the mean duration of pregnancy was 40.8 +or- 4.7 days. Women were given 200 mg of oral mifepristone, followed 48 hours later by 400 mcg of vaginal misoprostol. Oral misoprostol (400 mcg) was continued twice daily for 2 weeks. 11 women (55%) aborted during the initial 4-hour observation period and all had complete abortion. The mean duration of bleeding was 25.2 +or- 4.3 days. Nausea, diarrhea, and lower abdominal pain were the most common side effects of misoprostol, but all women were able to complete the 2-week course of treatment. On the basis of the findings of this pilot study, a prospective, randomized study with a larger number of patients is recommended to confirm whether a 2-week course of misoprostol can increase the abortion rate and decrease the duration of postabortal bleeding.

Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Administration, Intravaginal; Adolescent; Adult; Diarrhea; Female; Gestational Age; Humans; Mifepristone; Misoprostol; Parity; Pilot Projects; Pregnancy

Topics: Aged; Anti-Ulcer Agents; Diarrhea; Female; Humans; Misoprostol

The effectiveness of a combined regimen of mifepristone and vaginal misoprostol for termination of pregnancies of 9-13 weeks of gestation was investigated in 120 UK abortion patients (median age, 22.1 years; median duration of amenorrhea, 10.3 weeks). Each woman received a single oral dose of 200 mg of mifepristone 36-48 hours before admission, at which time 800 mcg of misoprostol was administered vaginally. Where indicated, a further two doses of 400 mcg of misoprostol (vaginal or oral) were provided every 3 hours. All 120 women aborted on the day of prostaglandin administration; however, 6 women (5%) required exploratory curettage after the procedure for retained placenta. The median prostaglandin dose was 1200 mcg (range, 800-1600 mcg). The median time from misoprostol administration to abortion was 4.33 hours (range, 1.3-16.0 hours). 60 women (50%) required oral analgesics and 26 (22%) received parenteral analgesia. Diarrhea occurred in 38 women (32%). The median duration of bleeding after abortion was 12.5 days (range, 3-43 days). In questionnaires administered to 73 women, only 3 (4%) expressed dissatisfaction with medical abortion, because of pain or prolonged bleeding. The relatively high dose of misoprostol used in this study and the vaginal route of administration are presumed to account for the 95% success rate. Extension of medical abortion to later gestation times would decrease the need for surgery and expand women's choice of methods of pregnancy termination.

Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Administration, Intravaginal; Administration, Oral; Adolescent; Adult; Analgesics; Diarrhea; Female; Follow-Up Studies; Gestational Age; Humans; Mifepristone; Misoprostol; Pain; Patient Satisfaction; Pregnancy; Pregnancy Trimester, First; Uterine Hemorrhage; Vomiting

Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Diarrhea; Drug Interactions; Drug Resistance, Microbial; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metronidazole; Misoprostol; Peptic Ulcer; Proton Pump Inhibitors; Salicylates; Salicylic Acid; Sucralfate; Tetracycline

Topics: Animals; Cobalt Radioisotopes; Diarrhea; Drug Administration Schedule; Drug Synergism; Gamma Rays; Iloprost; Lethal Dose 50; Male; Mice; Mice, Inbred Strains; Misoprostol; Radiation-Protective Agents; Superoxide Dismutase

To determine the mode of protective effects of misoprostol against the chronic gastrointestinal ulceration from the NSAID, diclofenac, studies were undertaken in domestic pigs, a model of human gastrointestinal ulceration, to determine (1) the effects of repeated daily dosing for 10 days of diclofenac 5 mg/kg/day twice a day (as Voltaren tablets) on the gastrointestinal morphology, 59fe-red blood loss, mucosal myeloperoxidase (MPO) activity (as an indicator of leukocyte infiltration), and mucosal leukotrienes (LTS); and (2) the mucosal protective effects of 10-40 micrograms/kg/day misoprostol twice a day (as Cytotec tablets) given with diclofenac 5 mg/kg/day twice a day compared with diclofenac 5 mg/kg/day alone and aspirin 150 mg/kg/twice a day (USP tablets) as a standard. These effects were compared with the dose range for potential diarrheagenic effects of misoprostol (determined by fecal analysis of NA+, K+, CL-, CA2+, H2O, and phenol red transit) given alone or with diclofenac to determine if this could be discriminated from antiulcer effects of misoprostol. Plasma and gastric mucosal concentrations of the drugs were determined to establish if misoprostol affects diclofenac absorption/elimination, and vice versa. The results showed that: (1) diclofenac produced gastric mucosal damage without any prior or concurrent bleeding from the gastrointestinal tract, although aspirin significantly increased blood loss; (2) misoprostol produced a dose-related reduction in diclofenac-induced mucosal damage of the upper gastrointestinal tract; (3) no significant increase in mucosal MPO occurred with diclofenac despite mucosal damage being evident, (4) mucosal LTS were unaffected by the drug treatments; (5) plasma, gastric and intestinal concentrations of diclofenac were not affected by misoprostol, while conversely plasma misoprostol concentrations were not influenced by the diclofenac treatment; (6) no significant effects on fecal water, electrolyte, or phenol red transit times were observed with an of the drug-treatments; and (7) mild diarrhea observed as "loose bowel motions" was only observed in most pigs receiving the misoprostol treatments during fasting on days 9-10. Thus, misoprostol protects against chronic lesions/ulcers in the upper gastrointestinal tract from diclofenac without: (1) signs of diarrhea becoming evident (the latter occurring when there is reduced food intake), (2) generalized leukocyte infiltration or effects on mucosal LTs, or (3) any re

Topics: Animals; Biological Availability; Diarrhea; Diclofenac; Digestive System; Gastric Mucosa; Intestinal Mucosa; Leukocytes; Leukotrienes; Male; Misoprostol; Peroxidase; Swine

To determine the effect of misoprostol, a synthetic prostaglandin E1 analogue, on the gastrointestinal tract (GIT) symptoms associated with non-steroidal anti-inflammatory drug (NSAID) administration and on the haemoglobin value, in children.. Retrospective chart review of children attending the paediatric rheumatology clinic at a tertiary referral hospital over a three year period, who were receiving NSAIDs and were prescribed misoprostol for treatment of GIT symptoms or anaemia.. Twenty five children (mean age 12.0 (SD 2.8) (range 7-17) years were prescribed misoprostol (mean dose 308.4 (76.5) micrograms/m2/day; 9.8 (2.5) micrograms/kg/day) while NSAID therapy was continued. Of the 22 (88%) patients with GIT complaints, 18 (82%) had complete resolution of symptoms and two (9%) had some improvement. Four patients (18%) had a recurrence of symptoms after initial resolution while still receiving misoprostol. Misoprostol therapy was associated with a statistically significant increase in haemoglobin concentration (mean value before misoprostol 115 (18) g/l; after misoprostol 126 (15) g/l (p = 0.02)). The only adverse effect reported was self limited diarrhoea in one child.. Misoprostol appeared to be effective in the treatment of GIT symptoms in children receiving NSAIDs and to result in significant increase in the haemoglobin concentration. Further prospective studies are needed to evaluate the role of misoprostol therapy for NSAID associated GIT complaints in the paediatric population.

Topics: Abdominal Pain; Adolescent; Anemia; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Child; Diarrhea; Female; Gastrointestinal Diseases; Hemoglobins; Humans; Male; Misoprostol; Retrospective Studies

Medically induced abortion using a new regimen of oral mifepristone 600 mg and vaginal misoprostol 800 micrograms (PGE1 analogue) was carried out in 100 women. Abortion occurred in all patients without resort to surgery. In 99 women, the abortion occurred within 4 hours of the administration of the prostaglandin. Sixty-seven patients did not request any form of analgesia. This regimen is highly effective, has a low incidence of side effects (mainly gastrointestinal) and appears to be highly acceptable to women.. Obstetrician-gynecologists recruited 100 women (mean age = 24.1 years and mean duration of amenorrhea = 51 days) attending the Aberdeen Royal Infirmary in Scotland to undergo elected abortion into an open study of the use of a new regimen of oral mifepristone (600 mg) and vaginally-administered misoprostol (800 mcg). This was the first pregnancy for 77 of the women. No surgical intervention was required in any of the cases. The conceptus was expelled and confirmed within 4 hours after administration of misoprostol in 99 women. The other woman aborted within 2 hours after an ultrasound scan. One women bled heavily and did not completely abort. She was readmitted to the hospital, where she received a blood transfusion. An oxytocic injection resulted in a complete abortion. One woman had a complete abortion with just mifepristone. Vomiting (17%) and diarrhea (12%) were the leading side effects. None of the women with these gastrointestinal effects needed any treatment. Most women (66%) did not ask for any analgesia. Bleeding after the abortion lasted on average 9.5 days. Before and after mean hemoglobin levels were similar (13.1 and 12.9, respectively). No one developed an infection. These findings support those of another study that misoprostol administered vaginally is much more effective at terminating pregnancy than when it is administered orally. They also show that women find vaginally administered misoprostol very acceptable.

Topics: Abortion, Induced; Administration, Oral; Adult; Diarrhea; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Time Factors; Vagina; Vomiting

SC-53450 is a new polybutadiene-based polymer system with an acid labile diisopropyl silyl ether linker to which the active isomer of misoprostol (SC-30249) is attached covalently at position C-11. It was studied in rats and dogs to define its profile of gastrointestinal effects relative to misoprostol-hydroxypropyl methylcellulose (HPMC) and the systemic availability of prostaglandin from the polymer. Results of rat studies indicate that SC-53450 has a spectrum of mucosal protective activity similar to misoprostol-HPMC, being protective against indomethacin-induced gastric, cysteamine/indomethacin-induced duodenal and indomethacin-induced lower small bowel damage. SC-53450, in contrast to misoprostol-HPMC, was not diarrheagenic in the rat when administered intragastrically. The observation that SC-53450 is more than 4 times more potent than misoprostol-HPMC suggests the possibility of sustained gastric availability of the prostaglandin SC-30249. SC-53450 exhibited gastric antisecretory activity in histamine-stimulated gastric fistula dogs and protected against acidified aspirin-induced gastric damage in normal fasted beagles. Rat and dog experiments indicate that little, if any, polymer-derived prostaglandin is available systemically, suggesting SC-53450 will have reduced abuse potential in abortion induction. SC-53450 is a potential candidate to replace the present misoprostol formulation in the marketplace for the prevention of nonsteroidal anti-inflammatory drug-induced gastric damage.

Topics: Animals; Antacids; Aspirin; Biological Availability; Butadienes; Depression, Chemical; Diarrhea; Dogs; Drug Carriers; Ethanol; Female; Gastric Mucosa; Hypromellose Derivatives; Indomethacin; Intestinal Diseases; Male; Methylcellulose; Misoprostol; Polymers; Rats; Rats, Inbred Strains; Stomach Diseases

The application of functionalized polymers to site-directed delivery of the antiulcer prostaglandin, misoprostol, is described. By use of homogeneous catalysis, the simple polymer, polybutadiene, was modified to incorporate the specialized requirements for controlled delivery of misoprostol to the stomach. An acid labile silyl ether bond to the C-11 hydroxyl of misoprostol was installed as the primary rate determining step for drug release, and a series of analogs, in which the steric hindrance about the silicon atom was varied, was prepared and evaluated for in vitro release rates, efficacy against indomethacin induced gastric damage and diarrheagenic activity. The diisopropylsilyl analog, the slowest releasing system studied, showed efficacy equal to misoprostol against indomethacin-induced gastric damage and no diarrhea at the highest dose tested.

Topics: Animals; Butadienes; Delayed-Action Preparations; Diarrhea; Drug Delivery Systems; Elastomers; Hydrogen-Ion Concentration; Male; Misoprostol; Polymers; Rats; Stomach; Structure-Activity Relationship

Topics: Aged; Crohn Disease; Diarrhea; Humans; Misoprostol; Risk Factors

We conducted a pilot study examining the relative preferences for various nonsteroidal antiinflammatory drug associated adverse gastrointestinal events and misoprostol prophylaxis for these events. Thirty patients with rheumatoid arthritis volunteered to participate. A trained nurse interviewer administered the structured pretested interview. Respondents rated 18 hypothetical health states on a category rating scale with anchors at 0 (immediate death) and 100 (full health for life). Linear contrasts were created to test the null hypotheses of equal preferences, using t tests for correlated means. Our results suggest that respondents place a high value on the avoidance of (in order of decreasing importance) surgery, hospitalization, prophylaxis induced diarrhea and uncomplicated ulcer requiring outpatient treatment. The avoidance of ulcer symptoms (primarily dyspepsia) and the inconvenience of an additional medication taken 4 times daily (in the absence of diarrhea) appeared to be substantially less important from these patients' perspective. Further work is underway to confirm these preliminary findings.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diarrhea; Female; Humans; Male; Middle Aged; Misoprostol; Patient Participation; Pilot Projects; Stomach Ulcer

Prostaglandin E (PGE) receptors in canine small intestinal mucosal and muscle membrane preparations were labeled with [3H] PGE1. Saturable, high affinity binding of [3H] PGE1 was observed in both preparations. The density of binding sites (fmol/mg protein) was 39 for mucosal membranes and 60 for muscle membranes, with corresponding dissociation constants of 10.6 nM and 5.8 nM, respectively. [3H] PGE1 binding sites in both preparations showed stereospecificity and high affinity for natural PGE1 and PGE2, but not for I or F-type PGs. Synthetic PGEs such as misoprostol and enisoprost had lower affinity than PGE1 or PGE2. Several analogs of enisoprost bound weakly to the binding sites. A highly significant correlation (C.C. = 0.9) was demonstrated between mucosal and muscle binding potency for a series of enisoprost analogs. There was also a significant positive correlation between the receptor binding potency and rat diarrheagenic activity for these analogs. These results indicate that PGE receptors in canine intestinal mucosa and muscle can be directly studied with [3H] PGE1 binding. The mucosal and muscle PGE receptors may have similar ligand binding specificity. We speculate that these receptors are likely to be associated with the diarrheagenic activity of PGEs.

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Diarrhea; Dogs; Intestine, Small; Male; Misoprostol; Molecular Structure; Rats; Receptors, Prostaglandin; Receptors, Prostaglandin E; Sensitivity and Specificity; Tritium

To report a case of profuse diarrhea after misoprostol use in a patient with a history of Crohn's disease and to discuss the role of eicosanoids in Crohn's disease.. Patient medical records, case reports, review articles identified by MEDLINE, and personal communication with the physician, patient, and manufacturer.. From interviews, the manufacturer, and pertinent published sources by one author and reviewed by the others.. A 55-year-old woman presented to clinic complaining of multiple joint pains. Her medical history was significant for peptic ulcer disease, hypertension, and Crohn's disease in remission since May 1989. Her joint pains were treated with ibuprofen 600 mg po qid and misoprostol 200 micrograms po qid (after meals and at bedtime). Following the administration of three doses of ibuprofen and misoprostol, the patient experienced abdominal cramps, pain, and voluminous, watery diarrhea for two days. Upon discontinuation of the ibuprofen and misoprostol, all of her gastrointestinal symptoms resolved within 12 hours. Rechallenge with ibuprofen alone failed to produce a recurrence of symptoms. Enhanced synthesis of intestinal eicosanoids has been demonstrated in Crohn's disease. Misoprostol, a synthetic analog of one of the eicosanoids, could induce a flare-up of Crohn's disease as suggested in this patient.. Misoprostol should be used with caution in patients with known inflammatory bowel disease.

Topics: Crohn Disease; Diarrhea; Eicosanoids; Female; Humans; Middle Aged; Misoprostol

Topics: Alprostadil; Animals; Cats; Diarrhea; Dinoprostone; Dogs; Enprostil; Ethanol; Female; Gastric Acid; Gastric Mucosa; Gastritis; Guinea Pigs; Histamine; Indomethacin; Misoprostol; Muscle, Smooth; Myometrium; Prostaglandins E, Synthetic; Rats; Receptors, Prostaglandin; Uterine Contraction

Topics: Alprostadil; Anti-Ulcer Agents; Colitis, Ulcerative; Crohn Disease; Diarrhea; Female; Humans; Male; Middle Aged; Misoprostol

Topics: Alprostadil; Anti-Ulcer Agents; Diarrhea; Humans; Misoprostol; Psyllium

Topics: Alprostadil; Anti-Ulcer Agents; Crohn Disease; Diarrhea; Female; Humans; Middle Aged; Misoprostol; Naproxen; Peptic Ulcer

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Diarrhea; Female; Humans; Misoprostol; Peptic Ulcer; Pregnancy; Stomach Ulcer

A stereospecific synthesis and the gastric antisecretory and diarrheal activity of a 3E,5Z diene analogue of misoprostol are described. The key intermediate in the synthesis was an alpha chain truncated acetylene that was obtained by a cuprate/enolate capture procedure on the corresponding cyclopentenone. Palladium-catalyzed coupling of the acetylene with methyl 4-iodo-3(E)-butenoate provided the conjugated enyne. Although selective hydrogenation of the enyne with Lindlar catalyst failed, the desired 3E,5Z diene was obtained with P-2 nickel as catalyst. The diene was about 3 times more potent than misoprostol in inhibiting gastric acid secretion in dogs and also in producing diarrhea in rats.

Topics: Alprostadil; Animals; Arbaprostil; Diarrhea; Dogs; Gastric Juice; Indicators and Reagents; Magnetic Resonance Spectroscopy; Male; Misoprostol; Prostaglandins E, Synthetic; Rats; Structure-Activity Relationship

Misoprostol is a synthetic prostaglandin which is related structurally to naturally occurring prostaglandin E1 (PGE1). PGE1 has long been recognized as an effective inhibitor of gastric acid secretion when administered intravenously. However, three major problems have prevented the use of natural PGE1 as a therapeutic treatment for peptic ulcer disease. Each of these problems, lack of oral activity, side-effects, and short duration of action, has been overcome by the chemical development of misoprostol from PGE1. The major structural alteration of PGE1 was the relocation of the 15-hydroxy group to the adjacent 16-position. This important modification significantly reduced typical prostaglandin side-effects such as diarrhea, yet retained full antisecretory potency and also provided a degree of oral activity. The second modification was the addition of a methyl group to carbon-16 to prevent metabolic oxidation of the hydroxy group. This structural change greatly increased both oral potency and duration of action and completed the synthetic development of misoprostol. Misoprostol is chemically unstable at room temperature, as is PGE1. This problem has been solved by pharmaceutical formulation studies which led to a stable and solid dosage form.

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Chemical Phenomena; Chemistry; Diarrhea; Drug Stability; Gastric Acid; Misoprostol; Prostaglandins E; Structure-Activity Relationship

Misoprostol, a synthetic derivative of prostaglandin E1, was tested and shown to be an effective gastric antisecretory agent against histamine-, pentagastrin-, and meal-stimulated acid secretion in dogs. Misoprostol reduced the volume of acid secretion as well as the hydrogen ion concentration. Misoprostol did not reduce gastric mucosal blood flow, nor did it alter meal-stimulated serum gastrin levels. Misoprostol inhibited acid secretion in histamine-stimulated isolated gastric glands indicating a direct antisecretory effect on parietal cells. The potency of misoprostol was greatest when administered in direct contact with the gastric mucosa indicating local absorption and action. Misoprostol strengthened the gastric mucosal barrier as shown by the attenuation of aspirin-induced lowering of transmucosal electrical potential differences. Misoprostol protected the gastric mucosa of rats subjected to ethanol-, taurocholate-, pyloric ligation-, stress- and indomethacin-induced damage. Misoprostol also protected against indomethacin-induced intestinal lesions in rats and reduced duodenal ulcer formation in guinea-pigs and cats. The doses of misoprostol required to protect against gastric damage were about one-tenth of those required to inhibit acid secretion. The results of these and other studies indicate that misoprostol is a safe agent with unique properties that should provide a new approach for treatment of ulcer diseases of the gastrointestinal tract.

Topics: Airway Resistance; Alprostadil; Animals; Anti-Ulcer Agents; Diarrhea; Drug Contamination; Drug Evaluation, Preclinical; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Hemodynamics; Isomerism; Membrane Potentials; Misoprostol; Regional Blood Flow; Stomach Ulcer

The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to the appropriate cyclopentenones. Although the trans and acetylenic derivatives were weak inhibitors of gastric acid secretion, the cis olefin was more potent and longer acting than the saturated parent compound. Selectivity with respect to unwanted diarrheagenic effects was found to be improved over that of both the parent 16-hydroxy compound and the reference standards, (15S)-15-methyl- and 16,16-dimethylprostaglandin E2.

Topics: Animals; Diarrhea; Dogs; Female; Gastric Mucosa; Histamine; Isomerism; Male; Prostaglandins E, Synthetic; Rats