Fomepizole 100mg/20ml solution for infusion ampoules

Objectives. The optimal antidote for the treatment of ethylene glycol or methanol intoxication is not known. The objective of this systematic review is to describe all available data on the use of ethanol and fomepizole for methanol and ethylene glycol intoxication. Data Source. A systematic search of MEDLINE and EMBASE was conducted. Study Selection. Published studies involving the use of ethanol or fomepizole, or both, in adults who presented within 72 hours of toxic alcohol ingestion were included. Our search yielded a total of 145 studies for our analysis. There were no randomized controlled trials, and no head-to-head trials. Data Extraction. Variables were evaluated for all publications by one independent author using a standardized data collection form. Data Synthesis. 897 patients with toxic alcohol ingestion were identified. 720 (80.3%) were treated with ethanol (505 Me, 215 EG), 146 (16.3%) with fomepizole (81 Me, 65 EG), and 33 (3.7%) with both antidotes (18 Me, 15 EG). Mortality in patients treated with ethanol was 21.8% for Me and 18.1% for EG. In those administered fomepizole, mortality was 17.1% for Me and 4.1% for EG. Adverse events were uncommon. Conclusion. The data supporting the use of one antidote is inconclusive. Further investigation is warranted.

Abstract licence: CC BY 3.0

Acetaminophen (APAP) overdose is the clinically most relevant drug hepatotoxicity in western countries, and, because of translational relevance of animal models, APAP is mechanistically the most studied drug. This review covers intracellular signaling events starting with drug metabolism and the central role of mitochondrial dysfunction involving oxidant stress and peroxynitrite. Mitochondria-derived endonucleases trigger nuclear DNA fragmentation, the point of no return for cell death. In addition, adaptive mechanisms that limit cell death are discussed including autophagy, mitochondrial morphology changes, and biogenesis. Extensive evidence supports oncotic necrosis as the mode of cell death; however, a partial overlap with signaling events of apoptosis, ferroptosis, and pyroptosis is the basis for controversial discussions. Furthermore, an update on sterile inflammation in injury and repair with activation of Kupffer cells, monocyte-derived macrophages, and neutrophils is provided. Understanding these mechanisms of cell death led to discovery of N-acetylcysteine and recently fomepizole as effective antidotes against APAP toxicity.

Abstract licence: CC BY

N-acetylcysteine (NAC) as the gold standard antidote in cases of acetaminophen (APAP)-related poisoning might not be sufficient with delayed presentation or massive ingestion. Human reports published up to July 2021 suggest that fomepizole could play a role in APAP overdoses by inhibiting cytochrome P450 2E1 (CYP2E1)-mediated N-acetyl-p-benzoquinone imine (NAPQI) production and JNK-mediated oxidative damage. This narrative review builds on previous systematic and scoping reviews by adding the latest evidence about the use of fomepizole in APAP poisoning to better understand the hepatoprotective role and safety profile of this medication, as well as its practical place in therapy. A systematic search of MEDLINE and Embase was completed through November 2024. Studies involving human patients with APAP toxicity who received fomepizole treatment were included. Each case was summarized in tables to identify clinical trends, particularly the risk of hepatotoxicity, quantity of ingestion, time of presentation since ingestion, therapeutic and dosing regimens, and clinical outcomes. This review covers 28 studies and 45 patients across 18 case reports and 6 case series. When used with NAC, fomepizole seemed to result in favorable laboratory and clinical outcomes in most patients at high risk of hepatotoxicity because of late presentation or massive APAP ingestion. The available data suggest that fomepizole might complement NAC in treating severe APAP toxicity. Though they lack detailed clinical outcome analyses, case studies suggest that fomepizole could improve hepatotoxicity, survival, and transplant-free days.

Abstract licence: CC BY-NC 3.0

Kejadian keracunan metanol sering karena konsumsi yang tidak disengaja atau disengaja. Paparan metanol sangat berbahaya, dengan morbiditas dan mortalitas yang signifikan jika tidak diobati. Perawatan utama keracunan metanol adalah etanol atau fomepizole. Fomepizol diakui lebih aman dan efektif dibandingkan etanol. Namun, hambatan penggunaan fomepizol adalah harganya mahal dan ketersediaannya yang terbatas di beberapa daerah, terutama di negara-negara berkembang. Dalam ulasan ini menjelaskan tentang pilihan antara penggunaan etanol dan fomepizol ketika fomepizol tidak tersedia. Studi ini merupakan studi tinjauan literatur. Literatur relevan yang digunakan untuk melakukan tinjauan literatur ini berasal dari database pubmed, dengan menggunakan kata kunci pencarian "Methanol"[tw] OR "Methanol poison*"[tw] OR "Methanol toxic*"[tw] OR "Methanol intoxic*"[tw]. Hasil dari penelusuran didapatkan 8 artikel yang memenuhi kriteria inklusi dan eksklusi untuk direview. Penghambatan alkohol dehidrogenase merupakan dasar untuk pengobatan keracunan metanol. Penanganan dasar keracunan metanol harus segera dilakukan dengan memberikan antidotum seperti fomepizol atau etanol untuk mencegah metanol termetabolisme menjadi metabolit yang dapat menyebabkan asidosis metabolik, kerusakan mata hingga kematian. Penanganan keracunan metanol menggunakan fomepizol ataupun etanol tidak menunjukkan perbedaan efektivitas klinis antara keduanya, meskipun fomepizol memberikan efek samping yang lebih baik. Etanol sebagai antidotum pada keracunan metanol masih dapat diberikan sebagai altenatif ketika fomepizol tidak tersedia.

Abstract licence: CC BY-NC 4.0