Real-world safety and effectiveness of intravenous fomepizole in patients with ethylene glycol and methanol poisoning in Japan: results of a 7-year post-marketing surveillance study.

BACKGROUND: Fomepizole is a competitive alcohol dehydrogenase inhibitor used for the treatment of ethylene glycol and methanol poisoning. We evaluated the safety and effectiveness of fomepizole in patients with ethylene glycol or methanol poisoning in Japan. RESEARCH DESIGN AND METHODS: This retrospective post-marketing surveillance study conducted in Japan registered patients who received fomepizole intravenous infusion per the package insert (January 2015-June 2022). Endpoints included adverse drug reactions/infections (ADRs), arterial blood pH, and treatment outcomes. RESULTS: Of 147 patients registered (91 institutions), 131 and 126 were included in the safety and effectiveness analysis set, respectively. Mean age was 43.6 years, and 66.4% were male. Mean time from poison ingestion to treatment was 15.1 hours; 66.4% received concomitant hemodialysis. No serious ADRs were reported. ADRs were reported in seven patients; the most-reported ADR was vomiting (2.3%). Seven patients died, 105 survived without sequelae, and 19 survived with sequelae. Most common sequelae were renal failure or renal dysfunction. Mean arterial blood pH increased to 7.4 by 4 hours of treatment, remaining stable for 24 hours post-treatment. CONCLUSIONS: Fomepizole is well tolerated and helps improve clinical outcomes in patients with ethylene glycol or methanol poisoning in Japan. TRIAL REGISTRATION: Japanese Pharmaceutical Information Center (JapicCTI-152817).

Simple triage and rapid decontamination of mass casualties with colored clothes pegs (STARDOM-CCP) system against chemical releases.

The efficiency and speed with which first responders, paramedics, and emergency physicians respond to an event caused by the release of a chemical is an important concern in all modern cities worldwide. A system for the initial triage and decontamination of victims of a chemical release was developed using colored clothes pegs of the following seven colors: red, yellow, green, black, white, and blue. Red indicates the need for emergency care, yellow for semi-emergency care, green for non-emergency care, black for expectant, white for dry decontamination, and blue for wet decontamination. The system can be employed as one of the techniques directed at improving the efficiency of decontamination in countries where there is a risk of chemical releases. It is recommended that this system should be adopted internationally and used for both drills and actual events.

[Post-marketing surveillance of acetylcysteine oral solution 17.6% "SENJU" for the antidote to acetaminophen overdose--use--results surveillance].

Use-result surveillance was conducted to investigate the safety and efficacy of Acetylcysteine Oral Solution 17.6 % "SENJU" having the indication for the antidote to acetaminophen (Paracetamol) overdose. Ninety six cases (patients) were collected for the safety evaluation, and 13 cases (incidence was 13.5 %) showed 29 adverse drug reactions as follows: 4 cases of nausea; 3 cases of vomiting; 2 cases each of liver dysfunction, headache, abdominal pain, diarrhea, blood bilirubin increased; and one case each of CK increased, anaemia, prothrombin time prolonged, gamma-glutamyltransferase increased, LDH increased, body temperature increased, proteinuria, blood potassium decreased, thrombocytopenia, platelet count increased, white blood cell decreased, and blood amylase increased. One case of severe liver dysfunction which was ameliorated later was found. Neither case showing transitional chronic liver dysfunction, nor case of death was observed. Patient background analysis showed that 79.2% of the total patients was female, and that 28.1% was patients with mental disease. Gastrolavage, active charcoal administration, and extracorporeal removal of toxins were performed in cases of 71.9%, 50.0% and 7.3%, respectively. Those concomitant treatments, however, showed no influence for the incidence of adverse drug reaction or the drug effectiveness. Blood acetaminophen assay was performed in only 43.8% of the total cases. This rate indicates that the medical treatment procedure needs more consideration on the clinical standard for the antidote to acetaminophen overdose and on its practical application.

[Simultaneous determination of propanil, carbaryl and 3,4-dichloroaniline in human serum by HPLC with UV detector following solid phase extraction].

In case of poisoning by herbicide compounded with Propanil (DCPA) and Carbaryl (NAC), we attempted simultaneous solid-phase extractions of DCPA, NAC, and 3,4-dichloroaniline (DCA), a metabolite of DCPA, from the patient's serum, and quantitative analytical method using HPLC-UV detection. With this HPLC method, the quantitative detection limits in the serum are 0.005 microgram/ml for DCPA and DCA and 0.001 microgram/ml for NAC, and the UV spectra of all three compounds could easily be obtained using a diode-array detection limit of 0.05 microgram/ml. When the three compounds were added to serum at concentrations ranging from 0.1-10.0 micrograms/ml, the recovery rates were satisfactory at between 91.1% and 101.9%. On analysis of the serum of patient who had ingested Kusanon A Emulsion, the ingested substance apparently caused an increase in the DCA concentration, which led to the appearance of methemoglobinemia. The possibility that the DCA concentration might be used for prognostic purposes was suggested.

[Clinical evaluation of triage as drug-of-abuse test kit].

There are about 60,000 chemical substances which may cause poisoning. Identifying the cause substances is, therefore, very important for patient at emergency department. Triage is an immunoassay kit for the qualitative test for the metabolites of 8 major abuse drugs in urine. We assessed the usefullness of Triage on two patient groups. The first Group consists of the patients considered having not taken substances at initial diagnosis; the second Group consists of the patients considered having taken substances. The result are as follows. 1) The rate of Triage positive patients in the first Group were: attempt-suicide 23%, coma 24%, shock 10%, trauma 7%, respectively. Except for the habitually used medicine, narcotic and stimulant drugs were detected. In the first Group, negative result of Triage was effective in diagnosing the patients as not poisoned, excluding the possitivity of 8 major drugs usage. 2) The rate of Triage positive patients in the second Group were very high: attempt-suicide 77%, coma 51%, shock 57%, trauma 30%, respectively, showing mostly any of 8 major drugs were the cause of poisoning. In the second Group, positive result of Triage was effective in diagnosing the patient as poisoning or as coexisting poisoning with other diseases. 3) The specificity of Triage diagnosis in the first Group was 80% (113/142). The specificity and the sensitivity in the second Group were 64% (50/78) and 97% (74/76), respectively. These results means that Triage is very useful for diagnosis on 8 major drugs poisoning. 4) Triage is efficient for identifying the cause substances in drug poisoning and, therefore, can save medical expense. Triage is a very useful test kit at emergency department.