Quality, availability and storage conditions of oxytocin and misoprostol in Malawi.

BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries (LMICs). Oxytocin and misoprostol are used for the prevention and treatment of PPH. However, both medicines are chemically unstable and sensitive to environmental conditions. Previous studies reported a high prevalence of substandard oxytocin and misoprostol preparations in LMICs. METHODS: In randomly selected health facilities of four districts of Malawi, the availability of oxytocin and misoprostol was determined, and the knowledge of health workers on storage requirements and use of oxytocics was assessed. Temperature loggers were used to record the storage temperature of oxytocics. Samples of oxytocin injections and misoprostol tablets were collected from the health facilities and from wholesalers. Oxytocin samples were analysed for identity, assay (= quantity of oxytocin) and for pH value according to United States Pharmacopeia 40. Misoprostol samples were analysed for identity, assay, dissolution and related substances according to the International Pharmacopeia 2017. RESULTS: All visited hospitals and health centers had oxytocin available. At non-refrigerated storage sites, the recorded mean kinetic temperature exceeded the oxytocic's storage temperature stated on the labels in 42% of the sites. At refrigerated storage sites, the required temperature of 2-8 °C was exceeded in 33% of the sites. Out of 65 oxytocin samples, 7 (11%) showed moderate deviations from specification, containing 82.2-86.8% of the declared amount of oxytocin. Out of 30 misoprostol samples, 5 (17%) showed extreme deviations, containing only 12.7-30.2% of the declared amount. The extremely substandard misoprostol was reported to the national authorities and to WHO, leading to an immediate recall of the respective brand in Malawi. The UK-based distributor of this brand closed its business shortly thereafter. CONCLUSION: Availability of oxytocin was excellent in Malawi, and its quality was better than reported in previous studies in other LMICs. However, storage conditions at the health facilities often did not meet the requirements. Extremely substandard misoprostol tablets were found, representing a serious risk to maternal health. This shows the need for continued efforts for quality assurance in medicine procurement and registration, as well as for post-marketing surveillance.

Randomised Trial of Oral Misoprostol Versus Manual Vacuum Aspiration for the Treatment of Incomplete Abortion at a Nigerian Tertiary Hospital.

OBJECTIVES: This study aimed to compare the efficacy of oral misoprostol with manual vacuum aspiration (MVA) in first trimester incomplete abortions. METHODS: This randomised controlled trial study was conducted at the University of Ilorin Teaching Hospital, Ilorin, Nigeria between April 2014 and November 2015. Pregnant women who presented with clinical features of incomplete abortion at a gestational age of 13 weeks or less were included. Patients who had profuse vaginal bleeding, an intrauterine device in situ, signs of pelvic infections or who were younger than 18 years old and had no accompanying adults to give informed consent were excluded. A total of 200 participants were randomly and equally allocated to either the MVA or misoprostol treatment group. The treatment group were given 600 µg of misoprostol orally. The primary outcome measure was complete uterine evacuation, while secondary outcome measures included the need for additional surgical evacuation for failed treatment, adverse effects/complications, acceptability of and satisfaction with the treatment. RESULTS: Both misoprostol and MVA had high complete evacuation rates, yet MVA was significantly higher (99% versus 83%, relative risk [RR]: 0.84, confidence interval [CI]: 0.766-0.918; P <0.001). Significantly more women in the misoprostol group required additional MVA for failed treatment than in the MVA treatment group (17% versus 1%, RR: 16.67, CI: 2.260-12.279; P <0.001). No significant difference was found between the misoprostol and MVA treatment groups in terms of satisfaction (92.7% versus 89.8%, RR: 1.04, CI: 0.946-1.127; P = 0.473). CONCLUSION: Treatments with misoprostol and MVA had high complete uterine evacuation rates, as well as high rates of acceptability and satisfaction. However, MVA had a significantly higher complete evacuation rate than misoprostol.

Quality medicines in maternal health: results of oxytocin, misoprostol, magnesium sulfate and calcium gluconate quality audits.

BACKGROUND: The high level of maternal mortality and morbidity as a result of complications due to childbirth is unacceptable. The impact of quality medicines in the management of these complications cannot be overemphasized. Most of those medicines are sensitive to environmental conditions and must be handled properly. In this study, the quality of oxytocin injection, misoprostol tablets, magnesium sulfate, and calcium gluconate injections was assessed across the six geopolitical zones of Nigeria. METHOD: Simple, stratified random sampling of health facilities in each of the political zones of Nigeria. Analysis for identification and content of active pharmaceutical ingredient was performed using high-performance liquid chromatography procedures of 159 samples of oxytocin injection and 166 samples of misoprostol tablets. Titrimetric methods were used to analyze 164 samples of magnesium sulfate and 148 samples of calcium gluconate injection. Other tests included sterility, pH measurement, and fill volume. RESULTS: Samples of these commodities were procured mainly from wholesale and retail pharmacies, where these were readily available, while the federal medical centers reported low availability. Approximately, 74.2% of oxytocin injection samples failed the assay test, with the northeast and southeast zones registering the highest failure rates. Misoprostol tablets recorded a percentage failure of 33.7%. Magnesium sulfate and Calcium gluconate injection samples recorded a failure rate of 6.8% and 2.4%, respectively. CONCLUSION: The prevalence of particularly of oxytocin and misoprostol commodities was of substandard quality. Strengthening the supply chain of these important medicines is paramount to ensuring their effectiveness in reducing maternal deaths in Nigeria.

Accessibility and potency of uterotonic drugs purchased by simulated clients in four districts in India.

BACKGROUND: Surveillance of drug quality for antibiotics, antiretrovirals, antimalarials and vaccines is better established than surveillance for maternal health drugs in low-income countries, particularly uterotonic drugs for the prevention and treatment of postpartum hemorrhage. The objectives of this study are to: assess private sector accessibility of four drugs used for uterotonic purposes (oxytocin, methylergometrine, misoprostol, valethamate bromide); and to assess potency of oxytocin and methylergometrine ampoules purchased by simulated clients. METHODS: The study was conducted in Hassan and Bagalkot districts in Karnataka state and Agra and Gorakhpur districts in Uttar Pradesh state. A sample of 877 private pharmacies was selected (using a stratified, systematic sampling with random start), among which 847 were successfully visited. The target sample size for assessment of accessibility was 50 pharmacies per drug, per district. The target sample size for potency assessment was 100 purchases each of oxytocin and methylergometrine across all districts. Successful drug purchases varied by state. RESULTS: In Agra and Gorakhpur, 90%-100% of visits for each of the drugs resulted in a purchase. In Bagalkot and Hassan, only 29%-52% of visits for each drug resulted in a purchase. Regarding potency, the percent of active pharmaceutical ingredient was assessed using United States Pharmacopeia monograph #33 for both drugs; 193 and 188 ampoules of oxytocin and methylergometrine, respectively, were assessed. The percent of oxytocin ampoules outside manufacturer specification ranged from 33%-40% in Karnataka and from 22%-50% in Uttar Pradesh. In Bagalkot and Hassan, 96% and 100% of the methylergometrine ampoules were outside manufacturer specification, respectively. In Agra and Gorakhpur, 54% and 44% were outside manufacturer specification, respectively. CONCLUSION: Private sector accessibility of uterotonic drugs in study districts in Karnataka warrants attention. Most importantly, interventions to assure quality oxytocin and particularly methylergometrine are needed in study districts in both states.

Where there are (few) skilled birth attendants.

Recent efforts to reduce maternal mortality in developing countries have focused primarily on two long-term aims: training and deploying skilled birth attendants and upgrading emergency obstetric care facilities. Given the future population-level benefits, strengthening of health systems makes excellent strategic sense but it does not address the immediate safe-delivery needs of the estimated 45 million women who are likely to deliver at home, without a skilled birth attendant. There are currently 28 countries from four major regions in which fewer than half of all births are attended by skilled birth attendants. Sixty-nine percent of maternal deaths in these four regions can be attributed to these 28 countries, despite the fact that these countries only constitute 34% of the total population in these regions. Trends documenting the change in the proportion of births accompanied by a skilled attendant in these 28 countries over the last 15-20 years offer no indication that adequate change is imminent. To rapidly reduce maternal mortality in regions where births in the home without skilled birth attendants are common, governments and community-based organizations could implement a cost-effective, complementary strategy involving health workers who are likely to be present when births in the home take place. Training community-based birth attendants in primary and secondary prevention technologies (e.g. misoprostol, family planning, measurement of blood loss, and postpartum care) will increase the chance that women in the lowest economic quintiles will also benefit from global safe motherhood efforts.

[New formulation of sublingual misoprostol (25 mcg) for induction of labor]. / Nova formulação de misoprostol sublingual na indução do trabalho de parto.

OBJECTIVES: To determine effectiveness and safety of sublingual misoprostol in tablets of 25 mcg, given every 6 hours for induction of labor in high-risk pregnant women hospitalized in two teaching hospitals in the Northeast of Brazil. METHODS: An open, non-randomized clinical trial was conducted, including 40 women with high-risk pregnancies hospitalized at "Maternidade-Escola Assis Chateaubriand" and "Instituto Materno-Infantil de Pernambuco". All of them had gestational age >or= 37 weeks, alive fetus with good vitality and Bishop scores

Nova formulação de misoprostol sublingual na indução do trabalho de parto / New formulation of sublingual misoprostol (25mcg) for induction of labor

OBJETIVO: Testar a efetividade e segurança do comprimido sublingual de misoprostol, na dose de 25 mcg a cada seis horas, para indução do parto em gestantes de alto risco internadas em dois hospitais-escola do Nordeste do Brasil. MÉTODOS: Realizou-se um ensaio clínico aberto, não randomizado, incluindo 40 gestantes de alto risco internadas nas Enfermarias de Patologia Obstétrica da Maternidade-Escola Assis Chateaubriand e Instituto Materno-Infantil de Pernambuco. Todas tinham idade gestacional maior que 37 semanas, feto único com boa vitalidade e escores de Bishop menores ou iguais a 7. Utilizou-se o comprimido de 25 mcg de misoprostol via sublingual, repetindo-se a cada seis horas, até no máximo de quatro doses. A análise estatística foi realizada no programa de domínio público Epi-Info 3.2.2. RESULTADOS: O trabalho de parto foi desencadeado em todas as gestantes. O intervalo entre a primeira dose e o início das contrações foi de 4,8±3,8 horas. O intervalo entre a primeira dose e o parto variou de 8 a 31 horas, com 95 por cento dos partos ocorrendo nas primeiras 24 horas, sendo 75 por cento por via vaginal. Houve necessidade de mais de uma dose de misoprostol em 60 por cento dos casos. A taquissistolia ocorreu em 12,5 por cento das gestantes. Não ocorreram complicações neonatais. CONCLUSÃO: O comprimido sublingual de 25 mcg de misoprostol foi efetivo para desencadeamento do trabalho de parto em gestantes de alto-risco. A eficácia desta nova via deve ser comparada à da via vaginal em futuros estudos clínicos randomizados.

A randomized trial comparing oral misoprostol with intra-amniotic prostaglandin F2alpha for second trimester terminations.

OBJECTIVE: To compare the efficacy of oral misoprostol with that of intra-amniotic prostaglandin F2alpha (PGF2alpha) for second trimester pregnancy termination. METHODS: One hundred seventeen women with pregnancies of between 16 and 22 weeks' gestation were randomly assigned after insertion of laminaria to receive either oral misoprostol 400 microg every 4 hours (to a maximum of four doses) or intra-amniotic PGF2alpha 40 mg. The rate of complete abortion within 24 hours was the primary outcome for power analysis. Secondary outcome measures were the rate of dilatation and curettage (D&C) for retained placenta and the rates of fever and gastrointestinal complications. RESULTS: Patient characteristics were similar in both groups. The rate of complete abortion within 24 hours was similar in the misoprostol (63%) and PGF2alpha (66%) groups. The rate of retained placenta requiring D&C was significantly greater in the PGF2alpha group (22.4% vs. 3.4%, P = 0.002). There were no differences in other maternal morbidities. Parous patients treated with oral misoprostol had a significantly greater rate of complete abortion than nulliparous patients (84% vs. 57%, P = 0.04). CONCLUSIONS: Oral misoprostol is as effective as intra-amniotic PGF2alpha for second trimester pregnancy termination when laminaria is inserted before treatment. Parous patients have a higher success rate than nulliparous patients with use of oral misoprostol. Oral misoprostol is associated with a very low rate of placental retention.

Misoprostol in gynecology.

Misoprostol is an important medication for gynecologic practice; however, it is not approved by the US Food and Drug Administration for any gynecologic indication. Evidence-based practice must guide our use of this important drug. Its use for medical abortion in conjunction with mifepristone or methotrexate is supported by a large body of high-quality evidence. There is also a rapidly growing amount of literature on the use of misoprostol for the management of miscarriage; however, more research is needed to optimize use. Solid evidence supports the efficacy of misoprostol for cervical ripening before first-trimester suction curettage abortion, and good evidence supports its use before hysteroscopy in premenopausal women; however, complications are rare with these procedures, making it difficult to assess any impact on complication rates. Most studies have not demonstrated a benefit for using misoprostol as a cervical ripening agent in postmenopausal women.

Early intrauterine pregnancy failure: a randomized trial of medical versus surgical treatment.

OBJECTIVE: The purpose of this study was to determine whether medical treatment of early pregnancy failure represents a reasonable alternative to surgical therapy. STUDY DESIGN: Patients who were diagnosed with pregnancy failure before 12 weeks of gestation were randomly assigned to receive either medical (intravaginal misoprostol) or surgical therapy (dilatation and curettage). In the medical arm of the study, 800 microg of misoprostol was placed within the posterior vaginal fornix. Patients subsequently were seen 24 and 48 hours after the initial dosing; intravaginal misoprostol was readministered only if ultrasound images revealed evidence of persistent pregnancy tissue. By 72 hours after initial study entry, if either a gestational sac or placental tissue was present, the medical treatment was considered a failure, and uterine curettage was performed. Statistical analysis was performed with the two-tailed unpaired t test, chi(2) analysis, Fisher exact test, and Mann-Whitney U test; a probability value of <.05 was considered statistically significant. RESULTS: A total of 50 women were enrolled, with 2 patients in the surgical arm experiencing spontaneous pregnancy loss before their scheduled procedures. Twenty-five women received medical therapy; 25 women were randomized to surgical procedure. Fifteen patients in the medical group (60%; 95% CI, 0.41-0.79) had successful pregnancy termination and did not require curettage. There were no significant differences between the medical and surgical groups with respect to either posttreatment hematocrit level or the time needed to achieve negative human chorionic gonadotropin test results. CONCLUSION: Intravaginal misoprostol is an effective agent for the treatment of early pregnancy failure. Medical treatment of early pregnancy failure represents a reasonable alternative to immediate surgical therapy.

A comparison of medical induction and dilation and evacuation for second-trimester abortion.

OBJECTIVE: The purpose of this study was to compare complication rates of patients who undergo dilation and evacuation or medical abortion between 14 and 24 weeks of gestation. STUDY DESIGN: We present a retrospective cohort study of 297 women who underwent either dilation and evacuation or medical abortion. Statistical methods included the Student t test, the chi(2) test, the Fisher exact test (where appropriate), and logistic regression. RESULTS: The overall complication rate was significantly lower in patients who underwent dilation and evacuation than in patients who underwent medical abortion (4% vs 29%; P <.001). Medical abortions with misoprostol resulted in a lower complication rate than abortions with other medications (odds ratio, 0.2; 95% CI, 0.1-0.4). More Laminaria was associated with a decreased risk of complications with surgical abortions (odds ratio, 0.9; 95% CI, 0.7-1.0). CONCLUSION: Dilation evacuation is the safest method of second-trimester abortion. Misoprostol is safer than other methods for medical abortion. Maximal use of Laminaria will decrease complication rates in surgical abortion.

Oral misoprostol versus vaginal gemeprost for cervical dilatation prior to vacuum aspiration in women in the sixth to twelfth week of gestation.

The effectiveness of oral misoprostol versus vaginal gemeprost for cervical dilatation prior to vacuum aspiration was compared in women in the 6th to 12th week of pregnancy. Sixty-four nulliparous women requesting termination of pregnancy between 6th to 12th weeks of gestation were randomized to receive either 400 micrograms misoprostol orally or 1 mg vaginal gemeprost at 12 hr or 3 hr prior to vacuum aspiration, respectively. The cervical dilatation at vacuum aspiration, the ease of the subsequent surgical procedure, and the incidence of complications and side effects were compared between these two methods of cervical priming. The median cervical dilatation at vacuum aspiration in the misoprostol group was significantly greater than that in the gemeprost group (8.0 mm versus 7.0 mm, p < 0.02). Preoperative side effects were significantly less frequent in the misoprostol group (p < 0.01). The ease of dilatation assessed subjectively by the operating surgeons was also improved significantly in the misoprostol group (p < 0.01). However, the duration of operation and blood loss were similar in both groups. Since misoprostol is also much cheaper and more convenient to use, we conclude that oral misoprostol is better than vaginal gemeprost for cervical dilatation prior to vacuum aspiration in first trimester pregnancy.

PIP: Given the importance of adequate cervical dilatation to vacuum aspiration abortion, the effectiveness of oral misoprostol and vaginal gemeprost was compared. The 64 study subjects, all in the first 6-12 weeks of pregnancy, were randomly assigned either to take 400 mcg of misoprostol the night before pregnancy termination or were given 50 mg of vitamin B6 (placebo for misoprostol) to be taken the night before the procedure followed by vaginal insertion of 1 mg of gemeprost three hours preoperatively. Preoperative side-effects--nausea, vomiting, abdominal pain, and vaginal spotting--were significantly greater (p 0.01) in the gemeprost group; 28 out of 32 women in the misoprostol group compared to only 17 out of 32 in the gemeprost group experienced no side effects. The mean baseline cervical dilatation of 8.1 mm in the misoprostol group was significantly greater (p 0.01) than that in the gemeprost group (7.0 mm) and the ease of further dilatation was rated by surgeons as easier than normal for 87.5% of women in the former group compared to 59.4% in the latter group (p 0.01). The duration of the procedure and mean blood loss were similar in both groups. In addition to being more effective than gemeprost, misoprostol is less expensive and stable at room temperature. This is the first prospective, randomized study of oral as opposed to vaginal administration of misoprostol for cervical dilatation.

Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol [corrected].

The efficacy and tolerability of mifepristone in combination with misoprostol for termination of early pregnancy (up to 49 days of amenorrhea) are established. We studied the efficacy and tolerability of this combination therapy for termination of pregnancy in women up to 63 days of amenorrhea. We also examined the effect of an additional dose of misoprostol in cases of nonexpulsion within 3 hours after the first dose. The multicenter trial included 1,108 women, mean age 27.9 +/- 6.2 years. The mean duration of pregnancy was 51.7 +/- 9.2 days. On day 1, the women received an oral dose of mifepristone, 600 mg. On day 3, they received an oral dose of misoprostol, 400 micrograms, and were monitored for up to 3 hours. If they did not expel the conceptus within 3 hours, an additional dose of 200 micrograms of misoprostol was given and they were monitored for 2 more hours. From days 10 to 18, the women were followed up with clinical examination, human chorionic gonadotropin measurement, or ultrasound examination. Overall, the procedure was successful in 92.9% of women. Efficacy decreased with the duration of pregnancy, especially after 56 days of amenorrhea. Up to 42 days of amenorrhea, the success rate was 97.6%; between days 42 and 49, 94.8%; between days 50 and 56, 93.4%; between days 57 and 63, 86.8%; and after day 63, 83.3%. The most common side effects were moderate uterine cramps (80.5%) and gastrointestinal (GI) symptoms (34.9%), especially vomiting (18.3%) and diarrhea (10.5%). GI symptoms were generally mild. A second dose of misoprostol was given to 61.6% of the women. In a subgroup analysis, we assessed the efficacy of 600 mg of mifepristone plus 400 or 600 micrograms of misoprostol (one or two doses) in women with up to 49 days of amenorrhea and compared it with the efficacy in women who received mifepristone plus only 400 micrograms (one dose) of misoprostol in a previous study. The overall rate of success (termination of pregnancy) was 95.5% in the current study compared with 95.4% in the previous study. The additional dose of misoprostol did not significantly increase the overall rate of success, but did increase the rate of termination within the monitoring period (69.7% versus 64.9% (and within 72 hours after administration of mifepristone (92.7% versus 90.4%). We have confirmed that the combination of mifepristone and misoprostol was effective, safe, and well tolerated for termination of pregnancies at 49 or fewer days of amenorrhea. The efficacy decreased slightly between 49 and 56 days, and then decreased significantly between 56 and 63 days. For maximal safety and tolerability, we recommend this method only for women with 49 or fewer days of amenorrhea. A second dose of misoprostol did not improve overall efficacy, but did increase the rate of early termination.

Termination of early pregnancy by two regimens of mifepristone with misoprostol and mifepristone with PG05--a multicentre randomized clinical trial in China.

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.

Methotrexate and misoprostol for abortion at 57-63 days gestation.

Methotrexate and misoprostol have been shown in preliminary studies to be effective for abortion at < or = 56 days gestation with minimal side effects. RU-486 is used in combination with prostaglandin for abortion < or = 49 days gestation in France but < or = 63 days gestation in England. This pilot study was performed to evaluate if methotrexate and misoprsotol may also be effective up to 63 days gestation. Ten pregnant women between 57-63 days gestation were treated with methotrexate 50 mg/m2 intramuscularly followed 3 days later by misoprostol 800 micrograms vaginally. Abortion occurred in 6 women; abortion occurred in one of the women after a repeat dose of misoprostol 24 hours after the first dose. The remaining 4 women all had a surgical abortion. In the successfully treated women, vaginal bleeding lasted 14 +/- 4 (mean +/- standard deviation) days and serum beta-hCG was < or = 25 IU/L by 32 +/- 5 days after the methotrexate injection. No methotrexate side effects occurred. Methotrexate and misoprostol do not appear to be as effective for medical abortion between 57 and 63 days gestation as compared to < or = 56 days gestation.

Arthrotec: a therapeutic option in the management of arthritis.

Arthrotec (Searle) is a new concept in NSAID therapy that provides powerful anti-inflammatory efficacy with enhanced upper GI safety. Arthrotec comprises an enteric-coated core of diclofenac sodium (50 mg) surrounded by a mantle of misoprostol (200 mcg). Two multicentre trials evaluated the efficacy of Arthrotec in rheumatoid arthritis (RA) and osteoarthritis (OA) patients who were randomised to receive either Arthrotec or diclofenac. The results of all arthritis assessments showed Arthrotec to be as effective as diclofenac in treating the signs and symptoms of RA and OA. Two endoscopic studies compared the antiarthritic efficacy and gastroduodenal safety of Arthrotec and diclofenac. In a 12-week study of RA patients, the antiarthritic efficacy of Arthrotec was equivalent to diclofenac; in addition, 60% fewer patients taking Arthrotec experienced ulcers than did those taking diclofenac (4.4% Arthrotec vs 11.1% diclofenac: P = 0.034). In a 4-week study of OA patients, Arthrotec's efficacy was equivalent to that of diclofenac and the Arthrotec group developed no ulcers, while 3.6% of the diclofenac group had ulcers (P = 0.015). In a trial conducted to compare the efficacy and upper gastroduodenal safety of Arthrotec with those of piroxicam and naproxen, patients with OA received either Arthrotec BID piroxicam 10 mg BID, or naproxen 375 BID for 4 weeks. Arthritis assessments showed Arthrotec to be at least as effective as piroxicam and naproxen in treating OA. Post-treatment endoscopy data indicated that gastroduodenal ulcers developed in 1.5% of patients receiving Arthrotec, 10.3% of patients receiving piroxicam, and 8.6% patients in the naproxen group.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of Arthrotec in the treatment of osteoarthritis.

In a double-blind study, 455 patients with osteoarthritis were randomly assigned to receive a combination of Arthrotec, 50 mg of diclofenac and 200 micrograms of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 4 weeks. At weeks 2 and 4 of treatment, no significant differences between the treatment groups were noted in changes from baseline on the physicians' and patients' global assessment of osteoarthritis. On a measure of arthritis severity, patients with both arthritis of the hip and knee showed improvement from week 2 to week 4, with no significant differences between treatment groups.

Efficacy of Arthrotec in the treatment of rheumatoid arthritis.

In a double-blind study, 346 patients with active rheumatoid arthritis were randomly assigned to receive Arthrotec, a combination of 50 mg of diclofenac and 200 *g of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 12 weeks. At weeks 4, 8, and 12 of treatment, no clinically significant differences between the two treatment groups were noted on measures of joint tenderness, pain, and swelling or on physicians' and patients' assessments of disease severity.