Preventive Efficacy and Safety of Rebamipide in Nonsteroidal Anti-Inflammatory Drug-Induced Mucosal Toxicity

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.

Eficácia da combinação fixa de timolol 0, 5% e brinzolamida 1% no tratamento do glaucoma primário de ângulo aberto e na hipertensão ocular / Efficacy of fixed combination of timolol 10% and Brinzolamide 1% for primary open angle glaucoma and ocular hypertension

OBJETIVO: Avaliar a eficácia e conforto dos pacientes portadores de glaucoma primário de ângulo aberto (GPAA) ou hipertensão ocular (HO) em uso da combinação fixa de timolol 0,5% e brinzolamida 1%. MÉTODOS: Foram acompanhados prospectivamente 26 pacientes portadores de GPAA ou HO, num total de 50 olhos que foram instituídos a utilizarem a combinação fixa de timolol 0,5% e brinzolamida 1%. As avaliações foram feitas por um único examinador por tonometria de aplanação (Goldman) em 7 e 30 dias. Os possíveis efeitos colaterais e intolerância foram descritos pelos próprios pacientes através da pergunta: "Você sentiu alguma alteração ao pingar a medicação prescrita?" Os dados foram coletados e analisados estatisticamente. RESULTADOS: Os valores de pressão intraocular (PIO) foram significativamente menores nas avaliações de 7 e 30 dias (p<0,001). A média da redução da PIO foi de 38%, variando de uma média inicial de 23,8 mmHg para 14,6 e 14,4 mmHg nos dias 7 e 30, respectivamente. Dos 26 pacientes incluídos apenas 4 relataram alguma queixa ao pingar o colírio, sendo que as queixas variaram de ardência, leve queimação e embaçamento. CONCLUSÃO: A combinação fixa de timolol 0,5% e brinzolamida 1% mostrou-se eficaz no tratamento de pacientes com GPAA e HO com eficácia semelhante a da literatura e apresentou um baixo índice de efeitos desconfortáveis relatados pelos usuários da medicação.

OBJETICVE: To evaluate the efficacy and side effects of timolol 0,5% and brinzolamide 1% fixed combination in patients with primary open angle glaucoma (POAG) and ocular hypertension (OH). METHODS: 50 eyes of 26 patients with POAG or OH were evaluated with topical therapy with fixed combination of timolol 0.5% and brinzolamide 1%.The measurements with Goldmann tonometry were applied by only one ophthalmologist after 7 and 30 days on medication. The side effects were described by the patient based on the following question: "Did you feel any alteration with the prescribed drops?" The data were collected and analized statistically. RESULTS: The intraocular pressure (IOP) was lower in 7 and 30 days (p<0.001).The mean reduction in IOP was 38% with a variation from 23,8 mmhg to 14.6 and 14.4 mmhg in 7 and 30 days. Four patients had side effects: burning and blurring vision were related. CONCLUSION: the fixed combination of timolol 0.5% and brinzolamide 1% had good results with lower IOP in the treatment of patients with POAG and OH just like in the literature and had few side effects.

Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase > or =15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of > or =15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respect to NSAID-warfarin interaction. In conclusion, special caution is required when an NSAID is administered to warfarin users if patients are taking warfarin >40 mg/week and other medications interacting with warfarin.

Meloxicam e prednisona: efeitos do tratamento oral de curto prazo sobre os níveis de pressão intraocular em cães / Meloxican and prednisone: the effects of orally short term treatment on the intra-ocular pressure levels in dogs

Para possível observação da hipertensão ocular com o uso de antiinflamatórios, foram selecionados 28 cães da raça Beagle. Para avaliação da pressão intra-ocular antes do tratamento, no dia 0 (zero) todos os animais tiveram a pressão intra-ocular avaliada às 08 horas e às 16 horas. No dia seguinte dez cães receberam meloxicam na dose de0,2 mg/kg, e 0,1mg/kg nos restantes quatro dias. Nove cães receberam prednisona na dose de 1,0 mg/kg durante cinco dias. Nove cães receberam somente porção de ração úmida. No quinto dia do tratamento todos os animais tiveram novamente a pressão intra-ocular avaliada às 08 horas e às 16 horas. Em todos os grupos, incluindo o grupo-controle, as maiores médias de pressão intra-ocular foram observadas no dia 5 (cinco). A diferença dos valores de pressão intra-ocular observada entre as medições das 08 horas e das 16 horas foi significativa, independente do tratamento e do dia considerado. O uso dos anti-inflamatórios esteroidal e não-esteroidal não foi capaz de causar hipertensão ocular e alguns fatores podem ser incriminados, como via de administração, dose e duração do tratamento utilizado, além da ausência de doença glaucomatosa nos cães selecionados

In order to observe a possible ocular hypertension associated with the use of anti-inflammatory drugs, 28 beagle dogs were selected. For evaluation of intraocular pressure before treatment, the totality of animals had their intraocular pressure measured at 8 a.m. and 4 p.m.on day 0 (zero). On the following day 10 animals received meloxican on dose of 0.2 mg/Kg and 0.1 mg/Kg on the four remaining days. Nine dogs received prednisone on dose of 1,0 mg/Kg during five days. Nine dogs received only wet feeding. On the fifth day of treatment the totality of dogs had their intraocular pressure measured at 8 a.m.and 4 p.m. For all groups, including control-group, the highest average values of intraocular pressure were observed on day 5 (five). The difference between the two evaluations of intra-ocular pressure (8a.m. and 4 p.m) was significant, independent of treatment and of the considered day. The use of both steroidal or non-steroidal antiinflammatory were not capable of causing ocular hypertension and some factors can be pointed out, such as route of administration, dosage and duration of therapy chosen, besides absence of glaucomatous disorder between the selected dogs

Tear film and ocular surface alterations in chronic users of antiglaucoma medications

PURPOSE: Tear film can be altered by chronic medications that may disrupt the equilibrium responsible for the functioning of the lacrimal gland and ocular surface. The purpose of this study was to determine if antiglaucomatous chronic treatment induced alterations in the tear film and ocular surface. METHODS: After informed consent, 21 patients using antiglaucomatous eye drops for more than 8 months and 20 age- and sex-matched volunteers without eye and systemic medications (control group) were enrolled. The data of ocular discomfort, fluorescein and lisamine green staining, tear film break-up time and Schirmer test were collected and compared by Student's t test. The impression cytology data were graded and compared by chi-square test. RESULTS: Patients chronically using antiglaucomatous medications presented with significant higher fluorescein staining (p=0.003), lisamine green staining (p=0.02) and lower TFBUT (p=0.001). The other comparedparameters, including impression cytology were similar between the treated and control group (p>0.05). CONCLUSIONS: The present study shows that the tear film and the ocular surface are altered in patients under antiglaucomatous medications. In common, all medications were preserved with benzalkonium chloride. Efforts to minimize the adverse effects of chronic use of antiglaucomatous drugs must be addressed.

OBJETIVO: O filme lacrimal pode ser alterado por medicações crônicas, que podem comprometer o equilíbrio responsável pela função da glândula lacrimal e da superfície ocular. O objetivo desse estudo foi determinar se o tratamento crônico com drogas antiglaucomatosas induz alterações no filme lacrimal e superfície ocular. MÉTODOS: Após o consentimento informado, 21 pacientes usando drogas antiglaucomatosas por mais de 8 meses e 20 voluntários com similar distribuição etária e por sexo, não usuários de medicação ocular ou sistêmica (grupo controle) foram incluídos. Os dados do desconforto ocular, coloração com fluoresceína e lissamina verde, tempo de ruptura do filme lacrimal e teste de Schirmer foram colhidos e analisados pelo teste t de Student. A citologia de impressão foi avaliada e comparada pelo teste de qui-quadrado. RESULTADOS: Pacientes usando cronicamente medicação antiglaucomatosa apresentaram ignificativamente maior coloração por fluoresceína (p=0,003), lissamina verde (p=0,02) e menor TRFL (p=0,001). Os outros parâmetros comparados, incluindo a citologia de impressão foram similares entre o grupo tratado e controle (p>0,05). CONCLUSÕES: Esse estudo demonstra que o filme lacrimal e a superfície ocular estão alterados em usuários de medicação antiglaucomatosa. Essas medicações apresentam em comum o cloreto de benzalcônio como conservante. Esforços para minimizar efeitos adversos do uso crônico de drogas antiglaucomatosas devem ser considerados.

Comparison of endoscopic gastric mucosa features after administration of piroxicam to meloxicam and their correlation with dyspepsia symptoms in elderly patient with knee osteoarthritis.

AIM: to know the effect of piroxicam (COX-1 and COX-2 inhibitor NSAID) and meloxicam (selective COX-2 inhibitor NSAID) against the gastric mucosa. METHODS: a random, double-blind-parallel study and repeat measurement against 20 elderly-patients with knee-OA was conducted. Patients were divided into 2 equal groups, every group got piroxicam 20 mg/day or meloxicam 15 mg/day for 3 weeks. On the second group, sukralfat 2 x 1 g/day were given. To examine the difference before and after treatment, we used Wilcoxon signed rank test, to examine the difference within those groups we used Mann-whitney U test, to examine the correlation between endoscopic score and dyspepsia, we used the Spearman correlation test with significant correlation interpretation by Guilford rules. RESULTS: one of piroxicam group was resigned, so that there was 19 person left to complete this study. Piroxicam has caused elevation of endoscopic score in 78% subject compared to the beginning of study, and 22% of the subject has developed ulcers. Alteration of endoscopic feature after administration of this piroxicam was statistically significant (p< 0,05). Mild dyspepsia symptoms after piroxicam administration were positive on 67% subjects (p< 0,05). After administration of meloxicam, 40% subjects have elevated endoscopic score compared to beginning of the study (p< 0,05). Mild dyspepsia symptoms after meloxicam administration were positive on 40% subjects (p> 0,05). Meloxicam has less elevation of endoscopic score compared to the piroxicam (p< 0,05). By statistics, both of groups showed no difference in dyspepsia symptoms (p> 0,05). There was no significant correlation between elevation of endoscopic score and dyspepsia on both of groups. Nevertheless, it tends to have weak positive correlation (piroxicam group r= 0,306, p> 0,05, meloxicam group r= 0,330, p> 0,05). CONCLUSION: on this study, we conclude that the administration of either piroxicam or meloxicam in elderly-patient with knee-OA has caused the gastric mucosa impairment. The impairment after meloxicam administration is milder than piroxicam. There is no significant difference of dyspepsia symptoms in both of groups. There is correlation between endoscopic gastric mucosa features with the dyspepsia symptoms.

Safety and efficacy of meloxicam 7.5 mg in the treatment of osteoarthritis in Thai patients.

A prospective, open trial to evaluate the safety and efficacy of oral meloxicam 7.5 mg once daily over a period of 28 days in Thai patients with osteoarthritis was conducted in 3 major hospitals in Bangkok, Thailand. A total of 137 patients were enrolled and completed the study protocol. The mean age of the patients was 57.6 years and 88 per cent were female. Pain on movement and pain at rest evaluated after treatment by visual analog scale (VAS) were significantly improved with respect to the baseline status (p<0.001). The final efficacy was reported as satisfactory or good in 97 per cent and 94 per cent as determined by patients and physicians respectively. Patient status evaluated at the end of the study reported improvement of their arthritic condition in 84 per cent. Drug tolerability assessed by patients and physicians and was good or satisfactory in 99 per cent and 98 per cent. GI adverse event was reported in 8.8 per cent. Other adverse events were itching/rash in 2.0 per cent and headache/insomnia in 1.5 per cent of patients. No patients withdrew from the study due to adverse events. No GI bleeding or perforation were observed. No hospitalization was observed during the study. There was no significant change of blood chemistry and hematological profile between pre and post treatment examination. Results from this study suggest that oral meloxicam 7.5 mg for 28 days is a safe and effective treatment regimen with high GI tolerability profile for the treatment of osteoarthritis in Thai patients.

Colestasis inducida por meloxican / Meloxicam-induced cholestasis

The cholestasis by meloxicam has not been often described. However, we present here the clinic, laboratory, histologic and follow up of a patient with cholestatic hepatitis produced by this drug.

Efeito do meloxicam sobre a lesäo de isquemia e reperfusäo em músculo esquelético de ratos / Effect of meloxicam on ischemia and reperfusion injury in skeletal muscle of rats

Os antiinflamatórios não esteroidais, derivados do piroxicam, agem como varredores de radicais livres de oxigênio em experimentos in vitro. O objetivo deste trabalho foi analisar o efeito do meloxicam em músculos esqueléticos de ratos submetidos à isquemia e reperfusão com base na análise de liberação de malondialdeído da membrana celular ( indicador de peroxidação lipídica provocada pelos radicais livres). Dezoito ratos Wistar foram divididos em 2 grupos de 9. O grupo I (grupo sham) foi tratado previamente com 3g/kg de peso de solução fisiológica e o grupo II com 3g/kg de peso de meloxicam por via peritoneal. Após 5 min os ratos foram submetidos a 3h de isquemia total ( torniquete) e 45 min de reperfusão das patas posteriores esquerdas. Colheram-se biópsias dos músculos isquêmicos e reperfundidos e das patas controles (contralaterais) para a dosagem de malondialdeído. A análise das diferenças de concentração do malondiadeído nas patas controles e reperfundidas no grupo I (43,7 +/- 60,7; n=9) em relação ao grupo II (21,7 +/- 49,5; n=9) não mostrou alteração significante (p=0,3). Os dados obtidos, neste trabalho, mostram que o meloxicam não protege a musculatura esquelética dos danos causados pela isquemia e reperfusão, com base na análise do malondialdeído tissular após 3h de isquemia e 45 min de reperfusão.

Fotosensibilidad por piroxicam / Piroxicam photosensitivity

Se comunica la experiencia en cuatro pacientes adultos que presentaron manifestaciones cutáneas estrechamente relacionadas al suministro por vía oral de piroxicam, analgésico y antiinflamatorio no esteroideo relacionado químicamente con los exicanes. Las lesiones cutáneas en todos ellos tuvieron caracteres muy similares, situándose en zonas expuestas como la cara y el dorso de las manos, con presencia de numerosas placas eritemato-vesiculosas, confluentes, acompañadas de ardor; surgieron a los poco días (entre 3 y 7) de tomar el medicamento. El estudio histológico mostró intensa reacción inflamatoria en la dermis y ampollas intraepidérmicas. La revisión de la literatura y lo observado en estos cuatro casos parecen indicar que lo anterior se debe a una reacción fotoalérgica y que las radiaciones ultravioleta de onda larga desencadenan el fenómeno

Pipotiazina de açäo prolongada e de administraçäo mensal no tratamento de manutençäo de esquizofrênicos em consultório particular com seguimento máximo de cinco anos / Prolonged action and monthly administration of pipothiazine in the treatment of schizophrenic patients in private clinic with maximum follow-up of 5 years

O objetivo deste trabalho foi avaliar a palmitato de pipotiazina no tratamento de manutençäo a longo termo em consultório particular. Quarenta e oito doentes foram seguidos por período de três a cinco anos. Interrupçäo do tratamento ocorreu em 44% dos casos, por motivos diversos e em maior proporçäo na fase inicial (<5 meses), confirmando deduçäo anterior sobre a importância da educaçäo contínua do doente e da família antes e no decorrer do tratamento. Os doentes que permaneceram em tratamento se beneficiaram com remissäo dos sintomas produtivos, melhora do relacionamento familiar e social, e muitos deles com a retomada das atividades. A dose média nas últimas quatro aplicaçöes foi de 53 mg IM. Reaçäo extrapiramidal ocorreu em baixa freqüência. O número de doentes utilizando antiparkinsoniano e seu consumo foram reduzidos no decorrer do tratamento. Amenorréia ocorreu em proporçäo elevada

Comparative study of piroxicam and ibuprofen in rheumatoid arthritis.

Piroxicam was compared with ibuprofen in a 8 weeks randomised open clinical trial in 31 patients (16 patients with piroxicam and 15 patients with ibuprofen) with rheumatoid arthritis. Piroxicam was given in a dosage of 20mg once daily and ibuprofen 400mg three times a day. Both drugs appeared to be equally effective and there were only few minor side effects in patients on either drug. The once daily administration gives piroxicam a clear practical advantage over ibuprofen.