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Toxicology

The role of fomepizole in acetaminophen-related poisoning: a narrative review

Frank Chen1, Shelly ZQ Lu2, Harleen Chohan2,3, Anthony Lau2,4orcid
Clinical and Experimental Emergency Medicine 2026;13(1):13-27.
Published online: August 13, 2025

1Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada

2Department of Pharmacy, Vancouver General Hospital, Vancouver, BC, Canada

3Solid Organ Transplant Program, Vancouver General Hospital, Vancouver, BC, Canada

4Department of Emergency Medicine, Vancouver General Hospital, Vancouver, BC, Canada

Correspondence to: Anthony Lau (Anthony.Lau@vch.ca)
• Received: March 11, 2025   • Revised: April 29, 2025   • Accepted: May 7, 2025

© 2026 The Korean Society of Emergency Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).

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  • 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.
  • Keywords: Acetaminophen; Antidotes; Fomepizole; Liver; Toxicology
What is already known
N-acetylcysteine as the gold standard antidote may not be sufficient in managing cases of acetaminophen (APAP)-related poisoning with delayed presentations or with massive ingestions. Previous scoping and systematic reviews of human data up until July 2021 have suggested that fomepizole may play a potential role in APAP overdoses through inhibition of cytochrome P450 2E1 (CYP2E1)-mediated N-acetyl-p-benzoquinone imine (NAPQI) and JNK-mediated oxidative damage, but they were unclear regarding the hepatoprotective benefits of fomepizole in treating APAP poisoning.
What is new in the current study
This narrative review summarizes the most recent evidence about using fomepizole in humans who have overdosed on APAP to offer new insights into its safety, effectiveness, and role in therapy.
Canada faces nearly 4,500 hospitalizations each year from acetaminophen (APAP)-related poisoning, with 6% of them resulting in liver injuries and acute liver failure requiring liver transplants or leading to death [1]. At therapeutic doses, 50% to 70% of APAP is metabolized by glucuronidation, 25% to 35% by sulfation, and 2% to 5% is excreted unchanged in urine [2]. The remainder undergoes liver metabolism, primarily by cytochrome P450 2E1 (CYP2E1), which generates toxic N-acetyl-p-benzoquinone imine (NAPQI), a key driver of APAP-induced hepatotoxicity [2]. At toxic doses (>4 g/day in adults or >75 mg/kg/day in children), the sulfation process becomes saturated, leading to excessive NAPQI production that depletes intracellular glutathione, causing oxidative liver damage. Fomepizole protects the liver by inhibiting CYP2E1, which reduces NAPQI formation, and blocking JNK activation to mitigate mitochondrial oxidative stress [2].
As the only available antidote for APAP-related poisoning, N-acetylcysteine (NAC) is most effective if initiated within 8 to 10 hours after an overdose, and it is successful in managing most toxic cases. However, with a massive ingestion (APAP levels above the 300 μg line on the Rumack-Matthew Nomogram or >30 g of ingestion) or late presentation (>8–10 hours), NAC alone might not prevent the need for liver transplantation or fulminant liver failure, prompting inquiries into whether additional therapy could be provided [2].
In the absence of robust studies, changes in standards of practice rely heavily on the body of evidence available in human case reports and case series. Previous systematic or scoping reviews summarized preclinical in vivo and in vitro data, along with human case studies on fomepizole in APAP-related poisoning only up to July 2021, and they offered preliminary and inconclusive insights into its use. This narrative review focuses on human experiences and includes several new case studies to identify emerging trends and patterns and better inform more specific recommendations for the indications and role of fomepizole in managing APAP poisoning.
Study design
This review summarizes the current evidence for the use of fomepizole to manage APAP overdose and toxicity. A systematic literature search was performed in the MEDLINE and Embase databases from their inception to November 2024 to identify relevant studies on this topic. The search strategy, developed with the assistance of a librarian, included Medical Subject Headings (MeSH) terms such as “fomepizole,” “acetaminophen,” “antidote,” “overdose,” and “toxicity” (Suppl. 1).
Selection of studies
The review included full-text studies and abstracts from conference proceedings that were written in English and involved the use of fomepizole as an antidote for patients with APAP overdoses. Animal studies, non-English publications, and studies exploring other indications of fomepizole, such as toxic alcohol ingestion in the absence of APAP overdose, were excluded. The references of reviews about fomepizole therapy for APAP toxicity management were hand-searched to identify any original articles that might otherwise have been missed. Two independent reviewers screened titles and abstracts, with a third resolving conflicts and discrepancies, and the data were extracted using a standardized form. Each article was thoroughly screened, and the study design, patient characteristics, treatment protocols, and key outcomes (recovery in liver function or injury, acid-base status, mental status, and timing of discharge) were extracted and summarized in tables. The risk of bias in each included study was identified using a full-text review and the JBI critical appraisal tool (Suppl. 2, 3).
Study analysis
A narrative synthesis was performed by identifying key themes that highlight human experiences with fomepizole protocols, including dosing, concomitant use with NAC and dialysis, timing of initiation, place in therapy (i.e., massive ingestion and late presentation), and effects on patient outcomes based on the risk of hepatotoxicity. No statistical analyses of the results were possible because of the large number of case series and heterogeneity in the data found.
The search strategy yielded 214 potentially relevant citations. After the removal of duplicate citations and initial screening, 51 studies were selected for full article review. Twenty-three studies were excluded after the full-text article review. Therefore, 28 publications were included, comprising 18 case reports and 6 case series describing 45 subjects, along with 1 randomized crossover trial, 1 registry-based study, and 2 conference abstracts [3–31]. One patient was excluded from a case series by Link et al. [21] due to duplication because the same case had already been reported by the same authors in 2020 [15]. Tables 1 and 2 provide more background on the included case studies. The studies sometimes reported a range of demographic characteristics, including age (mean age, 38.1 years), sex (female sex, 65%), dose of APAP ingested (median dose, 53.1 g), time to presentation from ingestion (median time, 5 hours), and various comorbidities among participants.
Among the 24 case reports and case series, most patients were deemed to have a high risk of hepatotoxicity and presented with massive APAP ingestion without other coingestants. In studies that reported the time between ingestion and presentation, the patient distribution was relatively equal between those who presented before and after the 8- to 10-hour mark after APAP ingestion. The most prevalent treatment regimen in these high-risk patients was dual therapy (NAC and fomepizole), with fomepizole most often initiated as a single dose more than 8 to 10 hours after APAP ingestion. Triple therapy (NAC, fomepizole, and dialysis) was also reported, often without indicating a preference for the timing of fomepizole, but in those cases, multidose regimens were seen more frequently than single-dose regimens. Single-dose-fomepizole monotherapy was also used in four of these cases, all of whom had APAP-aminotransferase multiplication product (APAP×AT) of more than 10,000 and developed shock or multiorgan dysfunction following chronic or repeated supratherapeutic APAP ingestions. The few patients who were at possible risk, low risk, or had an undetermined risk of hepatotoxicity typically presented within 8 to 10 hours after consumption and were successfully managed with either dual or triple therapy. In all but one patient, favorable clinical and laboratory outcomes were reported. Specifically, there was consistent resolution of neurocognitive, acid-base, and hemodynamic abnormalities without significant deterioration, organ failure, or the need for a liver transplant. APAP levels declined steadily throughout each patient’s clinical course, and the levels of liver enzymes and markers of liver function rose initially before recovering shortly after fomepizole initiation.
Regarding the ordinal aspect of each patient’s therapeutic regimen, fomepizole was most commonly started either at the same time as NAC or after NAC but before dialysis was initiated. On numerous occasions, the use of fomepizole was rationalized by either persistently elevated or increasing APAP and liver enzyme levels or the severity of patient presentation and possible coingestants prompting concerns about a significant risk of morbidity or near-term mortality. In all cases, fomepizole was most frequently administered at the dose standard for treating toxic alcohol poisoning (15 mg/kg intravenous [IV], followed by 10 mg/kg IV every 12 hours as needed). No adverse events associated with fomepizole were reported in any of these case reports or case series.
Our search also yielded a single double-blinded, randomized, controlled crossover trial, conducted by Kang et al. [27], which examined the effect of fomepizole alone on APAP levels in overdoses. The study involved five healthy volunteers. Participants received APAP alone or with fomepizole, with a 2-week washout period between treatments. Fomepizole significantly reduced the formation of oxidative metabolites, indicating its potential to mitigate APAP toxicity. However, that study's short timeline did not capture effects during peak hepatotoxicity, which occurs 72 to 96 hours after ingestion. No adverse events were reported.
A secondary analysis of the ToxIC (Toxicology Investigators Consortium) database by Filip et al. [28] between January 2015 and July 2020 revealed that when fomepizole was explicitly used to manage APAP-overdose patients (n=25) with markers of critical illness (hepatotoxicity/coagulopathy, metabolic acidosis, need for intubation/vasopressors/continuous renal replacement therapy), an overall mortality rate of 24% (6 of 25) was observed. It is interesting to note that this is higher than the mortality rates observed in the case reports and case series included in our review. However, the patients included in that study exhibited severely toxic clinical presentations, so its mortality rate was confounded by critical illness. Filip et al. [28] also explored prescriber attitudes about the use of fomepizole in that context. Most prescribers indicated that they would consider the use of fomepizole at the standard dose for managing toxic alcohol poisoning in conjunction with dialysis in both acute and chronic APAP overdoses. Most prescribers also agreed that fomepizole is safe in patients with significant metabolic acidosis or hepatotoxicity. No additional patient outcomes were derived from that study.
Two abstracts from conference proceedings are also included in this review. An institutional review of the use of fomepizole and NAC in patients with massive APAP ingestion and without co-ingestion of hepatotoxic substances (n=41) by Stott et al. [29] demonstrated that patients who started fomepizole and NAC on the same day had significantly lower peak AST levels and total days on NAC therapy than those who started the treatments on different days. A trend toward fewer deaths and major outcome designations was also observed in the same-day group. Vottero and Mégarbane [30] performed an observational retrospective cohort study in which mortality was observed in one of six patients who presented to a non-liver intensive care unit with acute liver failure and received both fomepizole and NAC.
To our knowledge, this review includes all the latest findings since July 2021 and adds to the available body of evidence summarized by recent systematic and scoping reviews by Mullins et al. [31] and Pourbagher-Shahri et al. [2]. It presents evolving insights into the hepatoprotective mechanisms, optimal dosing strategies, and safety profile of fomepizole in treating APAP poisoning. Prior to this narrative review, the benefits of adding fomepizole to NAC had been suggested by various in vitro and in vivo studies, but human data were quite limited. Thus, it remained unclear in both systematic or scoping reviews whether fomepizole alone or in combination with NAC was a primary contributor to each patient’s positive clinical outcomes [2,31]. Including studies from previous scoping reviews and new cases allowed for a more comprehensive overview of fomepizole use in APAP poisoning, revealing clinical trends and indications that were not addressed in earlier reviews.
Case series and case reports continue to offer insights into how fomepizole fits into patient care in the setting of APAP overdose in a real-life scenario, but observational cohort studies are needed to better understand the clinical outcomes of fomepizole in APAP toxicity management. Most care teams in these case reports did not pre-emptively initiate fomepizole with NAC upon initial toxic presentation. Fomepizole was typically started when APAP concentrations, liver enzyme markers, or a patient’s clinical status were not amenable to an IV NAC infusion. Instances in which fomepizole was initiated close to or at the same time as NAC seemed to occur often in patients who eventually required dialysis. This could imply that the severity of a patient’s toxic presentation factors into whether a clinician chooses to start fomepizole earlier as opposed to later. Beneficial clinical and laboratory effects were observed in these studies, but it remains unclear whether these outcomes can be attributed specifically to fomepizole alone or its use alongside NAC and hemodialysis or if fomepizole offered any significant hepatoprotection. Specifically, APAP concentrations and liver enzyme levels, along with other relevant laboratory markers (lactate, venous blood gas, bilirubin, international normalized ratio), seemed to decrease and become responsive upon the addition of fomepizole, but causality cannot be confirmed. Despite most cases resulting in the resolution of the patient’s general clinical presentation, liver/acid-base disturbances, and altered mental status, these studies did not provide in-depth analyses of their clinically meaningful outcomes. Nonetheless, these results suggest fomepizole’s potential role in improving hepatotoxicity in ways that reduce near-term mortality and the need for liver transplantation.
It has become clear that fomepizole is being used more liberally by prescribers for the management of APAP-related poisoning. The systematic review by Mullins et al. [31] recommended fomepizole as adjunctive therapy in patients with at least one of the following characteristics of severe poisoning: APAP concentration above the 300 line of the APAP treatment nomogram, metabolic acidosis, positive King’s College criteria, or late presentation with evident liver injury and measurable APAP levels. Among the 45 patients in the included case studies, the compiled trends and newly discovered themes across cases provide insight into additional criteria that could be used to determine when fomepizole therapy is warranted and how it could be administered. The severity of a patient’s clinical presentation and risk of mortality/morbidity were among the reasons most commonly cited in these case reports for initiating fomepizole as an adjunct to NAC or dialysis. APAP concentrations and liver enzymes or acid-base abnormalities that were not amenable to NAC infusions were also among the reasons fomepizole was started or multiple doses were administered. Although select cases did report that fomepizole monotherapy provided favorable patient outcomes, the limited clinical experience with this regimen precludes fomepizole from replacing NAC as the standard of care. Limited documentation in each case report makes it difficult to identify a specific timeframe in which the drug should be started. However, it is known that metabolism impairment occurs during an APAP overdose that results in a prolonged half-life of 4 to 8 hours [32]. That supports early initiation of fomepizole to take advantage of its hepatoprotective mechanisms during the APAP metabolism and post-metabolism phases, sourced from its CYP2E1 and JNK inhibition, respectively [33]. This consideration was also offered by Stott et al. [29], who showed that starting fomepizole preemptively on the same day as NAC could limit the severity of hepatotoxicity and reduce the time of NAC therapy. Thus, in addition to the recommendations made by Mullins et al. [31], fomepizole should be administered within 4 to 8 hours at the standard dose used in alcohol poisoning (15 mg/kg IV, followed by 10 mg/kg IV every 12 hours as needed) in patients at high risk of immediate mortality/morbidity. This includes those with severe clinical presentations, APAP levels above the Rumack-Matthew nomogram line, APAP×AT >10,000, and other markers of severe hepatotoxicity (e.g., refractory metabolic acidosis, coagulopathy, encephalopathy, acute kidney injury). Patients with APAP or liver enzyme levels that are not amenable to NAC infusion with or without dialysis should be considered for fomepizole therapy as well. Although fomepizole is removed by dialysis, there are major discrepancies on its dosing in patients receiving dialysis. Up to 42% of survey respondents in the study by Filip et al. [28] suggested that fomepizole redosing is required following dialysis. Fomepizole’s drug product monograph suggests that for alcohol intoxication, doses should be administered every 4 hours during dialysis [34].
No adverse events associated with fomepizole were documented in any case reports or case series included in this review. Furthermore, the lack of adverse events observed in the randomized-controlled trial by Kang et al. [27] and the extensive positive historical experience using fomepizole to treat toxic alcohol poisoning support its safe use in patients with APAP poisoning. Some common adverse reactions experienced with fomepizole, according to its drug monograph, include headache, nausea, dizziness, drowsiness, and metallic taste [34]. Less common side effects include abdominal pain, fever, injection site reactions, phlebitis, hypotension, vomiting, diarrhea, and facial flush [34]. A double-blind randomized-controlled trial by Jacobsen et al. [35] showed that in healthy volunteers, single doses of 10 and 20 mg/kg of fomepizole did not elicit any adverse effects. Doses above that caused mild to moderate and short-lived nausea, dizziness, and vertigo. No adverse effects linked to changes in objective readings (pulse, blood pressure, temperature, and blood/urine chemistries) were reported. However, the results of that study are limited by a lack of blinding to higher doses of fomepizole due to its poor palatability.
The cost of fomepizole as a novel therapy in APAP poisoning warrants consideration. Economic analyses have shown the inflation-adjusted cost of a single dose of fomepizole (15 mg/kg) to be US $748 to $1,123, which is similar to a 20-hour infusion of NAC (US $643 to $735) [36–40]. With the cost of liver transplants in the United States and other countries within the Organization for Economic Co-operation and Development (OECD) often exceeding US $150,000 to $200,000 and the cost of continuous renal replacement therapy, based on data from two tertiary intensive care units in Canada, ranging from CAD $3,486 to $5,117 per week, the potential hepatoprotective benefits of fomepizole could justify a more liberal use of this medication [41,42].
Limitations
Despite a promising place for fomepizole in patients with APAP overdoses, these results are confounded by a lack of standardization and consistency in treatment protocols, which hinders our ability to identify the main contributor to each patient’s clinical outcome. The assessment of each patient case was also complicated by a lack of documentation of pertinent clinical and laboratory information, which hindered our ability to make general inferences about hepatotoxicity risk stratification, the severity of APAP ingestion and toxic manifestation, the safety of fomepizole therapy, and trends in therapeutic interventions. The small sample sizes and lack of comparators in these case studies also limit their generalizability and undermine our ability to determine causative relationships. Selection bias and publication bias are also possible, with unusual or dramatic patient overdose cases being more likely to be published, so these cases probably do not reflect the entire spectrum of APAP overdose events. The included randomized-controlled trial, observational study, and reviews are also limited by small sample sizes and a lack of analyses for additional patient-centered outcomes. It was difficult to appraise the validity and integrity of each study in the abstracts sourced from conference proceedings. Future observational cohort studies would be an appropriate next step and will be essential to further define the hepatoprotective role of fomepizole and its effects on meaningful clinical outcomes in APAP overdose cases.
Conclusions
Human case studies and reports highlight the potential role of fomepizole as an adjunctive therapy in APAP poisoning, particularly in patients for whom intravenous NAC alone is insufficient. Although fomepizole is not a replacement for NAC as the standard of care, it might have contributed to the beneficial outcomes seen in severe poisoning cases, including those with high APAP concentrations, metabolic acidosis, or signs of liver injury. Historical experience with fomepizole in toxic alcohol poisoning and the limited evidence sourced from the randomized, controlled crossover trial suggest that fomepizole exhibits a good safety profile with limited adverse effects. Overall, the evidence supports fomepizole’s consideration in select scenarios, especially in cases with a high risk of hepatotoxicity, severely toxic or refractory clinical status, or late presentation after APAP ingestion. However, in cases of rapid clinical deterioration, a low threshold for hemodialysis remains essential, emphasizing the need for further research to support fomepizole’s role in APAP toxicity management.

Author contributions

Conceptualization: AL, SZQL, HC; Data curation: AL, HC, FC; Writing–original draft: FC, AL; Writing–review & editing: all authors. All authors read and approved the final manuscript.

Conflicts of interest

The authors have no conflicts of interest to declare.

Funding

The authors received no financial support for this study.

Data availability

Data analyzed in this study are available within the article and its supplementary materials.

Supplementary materials are available from https://doi.org/10.15441/ceem.25.059.

Suppl. 1.

Search strategy used for literature search in selected MEDLINE and Embase databases
ceem-25-059-Supplementary-Material-1.pdf

Suppl. 2.

Critical appraisal of included case reports
ceem-25-059-Supplementary-Table-1.pdf

Suppl. 3.

Critical appraisal of included case series
ceem-25-059-Supplementary-Table-2.pdf
Fig. 1.
PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) flowchart for the literature search in MEDLINE and Embase.
ceem-25-059f1.jpg
Table 1.
Summary of included case reports about fomepizole use in acetaminophen overdose
Table 1.
Study Age (yr) Sex Medical history, presentation, timing Ingestion dose and timing (if known) Intervention and timing of interventions after ingestion unless stated otherwise (if known) Laboratory findinga)
 Clinical course
APAP level Liver enzyme level
Williams et al. [3] (2024) 18 Male Depression, anxiety, borderline personality disorder APAP 125 g (1 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV ×3 days  At 4 hr: 738 μg/mL (undetectable at 57 hr) Day 2: AST, 50 U/L Developed shock, decline in mental status, acidosis at 5 hr
Nausea, vomiting 5 hr: intubation, norepinephrine, vasopressin Day 4: ALT, 55 U/L Mental status, liver enzymes returned to baseline on day 3, and no permanent liver toxicities developed
9 hr: fomepizole 15 mg/kg IV, hemodialysis for 4 hr ×3 days
16 hr: CRRT for 4 hr, NAC 70 mg/kg PO every 4 hr, fomepizole decreased to 10 mg/kg IV every 6 hr
Chary et al. [4] (2023) 50 Female SUD - Preadmission: naloxone 4 mg IN and 2 mg IV  Days 1–3: 200 to >530 μg/mL (<100 μg/mL on day 5) Days 3–4: Patient developed grade III encephalopathy and started CRRT on day 5
Unresponsiveness, somnolence, ethanol 293 mg/dL Admission: NAC 150 mg/kg IV, then 12.5 mg/kg/hr IV for 4 hr, then 6.25 mg/kg/hr IV for 16 hr AST, >6,000 U/L (normalized on day 5) Developed neutropenia, and filgrastim was started on day 6
After NAC: intubation ALT, 6,600 U/L Mental status improved by day 7 and returned to baseline by day 10
Day 4: fomepizole 15 mg/kg IV and cryoprecipitate 6 U 12 hr after
Day 5: fomepizole 10 mg/kg IV, CRRT
Day 6: filgrastim 300 μg
Lobo et al. [5] (2023) 59 Male Encephalopathy APAP 100 g, ibuprofen 100 g (5 hr prior) Timing unknown: NAC, fomepizole 15 mg/kg IV  At 24 hr: 535 μg/mL (undetectable at 105 hr) Timing unknown: Patient discharged on day 25
After transfer to tertiary facility: NAC 12.5 mg/kg/hr IV, fomepizole 10 mg/kg IV ×5 doses ALT, 123 U/L (normalized at 97 hr)
31 hr: CRRT ×24 hr AST, 100 U/L (normalized at 5 hr)
Pepin et al. [6] (2023) 7 mo Female Fever, vomiting, cough, encephalopathy APAP 4.8 g, ibuprofen (over 5 days) Timing unknown: NAC 150 mg/kg IV over 1 hr, then 50 mg/kg IV over 4 hr, then 100 mg/kg IV over 16 hr  Timing unknown: 239.6 μg/mL (1 μg/mL on day 5) 8 hr after admission: AST, >27,300 U/L (216 U/L on day 6) Worsening agitation observed on day 4
8 hr after admission: fomepizole 15 mg/kg IV ALT, >11,700 U/L (2,403 U/L on day 6) NAC was stopped on day 4, and patient returned to mental baseline on day 5 and was discharged on day 8
After fomepizole: fresh frozen plasma, platelets, aminocaproic acid 500 mg, vitamin K 3 mg IV
After transfer to transplant facility: fomepizole 10 mg/kg IV every 12 hr ×3 doses, NAC 12.5 mg/kg/hr IV ×81 hr
Ho and Brambl [7] (2023) 37 Male Tachycardia, hypothermia, tachypnoea, hypertension, acidemia, hepatotoxicity, possible alcohol ingestion - Timing unknown intubation, activated charcoal 50 g, NAC 140 mg/kg PO, NAC 150 mg/kg IV then 24 mg/kg/hr IV, fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr ×4 doses  On admission: 707 μg/mL (undetectable on day 3) Day 2: transaminases, >3,000 U/L Despite fomepizole, charcoal, NAC, and hemodialysis, patient continued to be acidotic and developed significant hepatotoxicity
12 hr after admission: hemodialysis Other outcomes were not documented
Kusnik et al. [8] (2022) 58 Female Fibromyalgia, AUD Unknown quantity (6–18 hr prior) 6–18 hr: NAC ×21 hr, multivitamins, pantoprazole  On 6–18 hr: 126.3 μg/mL (undetectable at 40 hr) Days after 27 hr: Kidney function improved 80 hr after admission without hemodialysis
Altered mental status, abdominal pain ×2 days, AKI 15–27 hr: NAC increased to 12.5 mg/kg/hr IV, then decreased to 6.25 mg/kg/hr IV after APAP undetectable AST, 34,665–13,995 U/L (normalized ≈4 wk after admission) Encephalopathy improved 1 day after admission
36–48 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr given at 30, 45, 57, 69, and 81 hr Liver and kidney function returned to baseline 4 wk after admission
Timing unknown: albumin, midodrine, octreotide
Bassi et al. [9] (2022) 23 Male Agitation, laryngospasms APAP 188.5 g, naproxen, ibuprofen, hydrocodone, loratadine (1–3 hr prior) Admission: NAC 200 mg/kg IV over 4 hr, then 100 mg/kg IV over 16 hr, activated charcoal 50g 20 hr after admission: 287 μg/mL (undetectable at 96 hr) AST (timing unknown): 209 and 298 U/L Recovered without liver transplant
34 hr: NAC infusion rate doubled, fomepizole 15 mg/kg IV, activated charcoal 50g
47 hr: endoscopy
Before transfer to transplant facility: CRRT
Dion et al. [10] (2022) 17 Male Undiagnosed eating disorder APAP 50–75 g, caffeinated drink, sennosides (2 hr prior) 3 hr: NAC 300 mg/kg IV, fomepizole 15 mg/kg IV  At 12 hr: 391.8 μg/mL (2.8 μg/mL at 60 hr) No significant increases in liver enzymes were observed Abdominal pain resolved by day 3, and patient was cleared for discharge on day 4
Abdominal pain, altered mental status, apnea Day 2: fomepizole 15 mg/kg IV, NAC 300 mg/kg IV ×48 hr
Chiu et al. [11] (2021) 20 Female Anxiety, self-harm/prior suicide attempts APAP >120 g, ibuprofen 65 g, oxycodone 300 mg (2 hr prior) Timing unknown: intubation, norepinephrine 0.3 μg/kg/min ×2 days, epinephrine 0.2 μg/kg/min ×2 days, sodium bicarbonate  At 7 hr: ≈680 μg/mL (undetectable at 32 hr) Admission day 2: ALT 76 U/L 24 hr after admission, patient was awake and oriented and followed commands
Tachycardia, refractory shock, altered LOC, metabolic acidosis 3 hr: activated charcoal, NAC 150 mg/kg IV then 15 mg/kg/hr IV ×3 days, fomepizole 1,000 mg IV (10 mg/kg IV every 4 hr during dialysis and for an additional day 700 mg IV every 12 hr; total 2 days of fomepizole) Metabolic acidosis was refractory to NAC and fomepizole, requiring dialysis
6 hr: hemodialysis Acid-base/hemodynamic status returned to baseline without organ failure
Homan et al. [12] (2021) 58 Female AUD, hypertension, hyperlipidemia, hepatic steatosis - Timing unknown: fluids, NAC, fomepizole (unknown dose), lactulose, rifaximin, vitamin K, albumin, octreotide, midodrine  Unknown timing: 58.3 (units unknown) Unknown timing: AST, 19,816 Pancreatitis, coagulopathy, and hepatorenal syndrome developed
Abdominal pain, nausea, vomiting, lethargy, encephalopathy, RUQ tenderness ALT, 5,544 (units unknown) Mental status and laboratory abnormalities improved gradually, and APAP levels became undetectable
Cuninghame et al. [13] (2021) 24 Female Endometriosis, chronic pelvic pain, depression, anxiety, previous suicide attempts APAP 50 g, gabapentin 25.5 g, morphine 60 mg (16 hr prior) 16 hr: NAC 60 mg/kg IV then 12 mg/kg/hr IV, fomepizole 600 mg IV q6 hr  18 hr: 602 μg/mL (undetectable on admission day 8) 88 hr: transaminases >8,000 U/L Fulminant liver failure progressed with cerebral edema, encephalopathy, hypoglycemia, petechial hemorrhage, diffuse axonal injury, coagulopathy
Altered mental status, metabolic acidosis 18 hr: intubation Altered mental status and metabolic acidosis were refractory to all interventions
43 hr: hemodialysis First case report of fatal APAP ingestion refractory to both hemodialysis and CRRT at time of writing
56 hr: second hemodialysis run
66 hr: CRRT
48 hr after CRRT: whole bowel irrigation, colonic decompression
16 days after admission: life-sustaining measures withdrawn
Woolum et al. [14] (2020) 55 M with Male Type I bipolar depressive disorder, previous suicidal ideation, diabetes, CKD stage III APAP 65 g (7 hr prior) Before admission: naloxone 1.5 mg IV  At 7 hr: 883 μg/mL (undetectable on admission day 3) Admission day 2: AST, 1,791 U/L Patient was discharged after 4 days of hospitalization without systemic, hepatic, or mental abnormalities
Unresponsive Admission: intubation, NAC 6.25 mg/kg/hr IV, sodium bicarbonate, fomepizole 15 mg/kg IV ALT, 743 U/L (normalized ≈4 days after admission)
3 hr after admission: hemodialysis ×3 hr, NAC increased to 18.75 mg/kg/hr IV ×3 days
Link et al. [15] (2020) 45 Male - - 4 hr after admission: NAC 150 mg/kg IV, then 12.5 mg/kg/hr IV, then 18.75 mg/kg/hr IV at 8 hr (stopped at 35 hr), fomepizole 15 mg/kg IV, then 15 mg/kg IV at 16 hr, then 10 mg/kg IV at 28 hr  4 hr after admission: 791 μg/mL (<74.5 μg/mL at 28 hr after admission) ALT remained WNL No liver injuries were sustained, and liver enzymes, neurocognition returned to baseline on day 8
8 hr after admission: CRRT until 23 hr
Hidalgo et al. [16] (2020) 18 Female Lethargy APAP 46 g (10 hr prior) 10 hr: NAC IV  At 10 hr: > 250 μg/mL (undetectable 18 hr after dialysis) At 58 hr: Discharged after 6 days without issues
After NAC: fomepizole 15 mg/kg IV, hemodialysis ×4 hr AST, 3,820 IU/L
After dialysis: fomepizole 10 mg/kg IV ALT, 4,346 IU/L
After second dose of fomepizole: CRRT (normalized at unknown time)
Shah and Beuhler [17] (2020) 33 Male AUD APAP 25 g (taken over past 2 days) 9 hr after admission: NAC 150 mg/kg IV, then 12 mg/kg/hr IV ×4 hr, then 6.25 mg/kg/hr IV ×9 hr  Admission: 337 μg/mL (20 μg/mL at 42 hr) Admission day 3: Patient was medically cleared and did well
Abdominal pain, tachycardia, tachypnea 11 hr after admission: fomepizole 15 mg/kg IV AST, 198 U/L
ALT, 301 U/L
Kiernan et al. [18] (2019) 64 Female Comatose, anion gap metabolic acidosis, lactatemia APAP 104 g, diphenhydramine 5.2 g (3 hr prior) 3 hr: intubation, epinephrine 100 μg IV, dopamine 10 μg/kg/min IV then 15 μg/kg/min IV, norepinephrine 10 μg/min IV  At 3 hr: 1,017 μg/mL (< 15 μg/mL at 48 hr) At 3 hr: Complete resolution of metabolic acidosis and coma without hepatitis or sequelae, discharged 8 days after admission
After initial therapy: sodium bicarbonate IV AST, 21 IU/L;
2 hr after first APAP level: NAC 200 mg/kg IV during dialysis 300 mg/kg IV at 15 hr and 100 mg/kg IV at 16 hr ALT, 99 IU/L
7 hr after first APAP level: fomepizole 15 mg/kg IV then 10 mg/kg IV at 15 hr
10 hr after first APAP level: hemodialysis ×6 hr
Villano et al. [19] (2015) 28 Male Depressed LOC, unresponsiveness, tachycardia, tachypnea, acidemia Unknown dose (16 hr prior) Timing unknown: fomepizole (unknown dose), NAC ×45 hr  At 16 hr: 616 μg/mL At 16 hr: ALT, 27 U/L Recovery was made without hemodialysis
After initial labs: AST, 67 U/L
Zell-Kanter et al. [20] (2013) 59- Female Depression - Timing unknown: intubation, activated charcoal 1/kg, sodium bicarbonate 1–2 mEq/kg, NAC ×59 hr, naloxone, fomepizole ×1 dose (unknown dose)  Several hours after initial readings: 1,193 mg/L Admission day 2: Patient treated successfully by admission day 4
Obtunded, agonal respirations AST, 3,150 U/L
ALT, 2,780 U/L (normalized on admission day 4)

APAP, acetaminophen; NAC, N-acetylcysteine; IV, intravenous; CRRT, continuous renal replacement therapy; PO, per oral; AST, aspartate transaminase; ALT, alanine transaminase; SUD, substance use disorder; IN, intranasal; AUD, alcohol use disorder; AKI, acute kidney injury; LOC, loss of consciousness; RUQ, right upper quadrant; CKD, chronic kidney disease; WNL, within normal limits.

a)Highest reported level.

Table 2.
Summary of included case series about fomepizole use in acetaminophen overdose
Table 2.
Study Age (yr) Sex Medical history and presentation Ingestion dose and timing (if known) Timing of interventions after ingestion unless stated otherwise (if known) Laboratory findinga)
 Clinical course
APAP level and APAP × AT Liver enzyme level
Link et al. [21] (2022) (n=7) 47 Female Lightheadedness, confusion, hypoglycemia APAP 1 g every 4 hr ×2–3 days (12 hr prior) 16 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 16 hr: 10.8 μg/mL 29 hr: ALT, 3,325 U/L (118 U/L at 258 hr) AKI developed during hospitalization and was managed with CRRT
Several hours after NAC: intubation, norepinephrine, vasopressin, angiotensin II APAP × AT, 26,322 41 hr: AST, 9,305 U/L (77 U/L at 258 hr) Patient developed hypotension requiring vasopressors
After intubation/vasopressors: CRRT A full recovery was made, and no liver failure was observed at discharge
24 hr: fomepizole 15 mg/kg IV ×4 doses at 24, 36, 57, 70 hr
43 Female HIV, SUD, depression, epilepsy APAP 5 g (12 hr prior) 19 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 19 hr: 18 μg/mL 30 hr: A full and rapid recovery was made, and the patient was discharged without new impairments
Hemorrhoidal pain 31 hr: fomepizole 15 mg/kg IV APAP × AT, 50,620 ALT, 3,555 U/L Transaminases recovered quickly
AST, 12,655 U/L
114 hr:
ALT, 382 U/L
AST, 64 U/L
18 Female APAP 25 g, diphenhydramine 300–600 mg (4 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg IV 4 hr: 159 μg/mL 4 hr: 159 μg/mL No significant liver injury occurred
8 hr: fomepizole 15 mg/kg IV ×2 doses at 8 and 21 hr APAP × AT, 2,560
51 Female ESRD, diabetes, COPD, depression, intimate partner violence APAP 6.5–9.75 g (4 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 4 hr: 313 μg/mL 18 hr: Transaminases improved quickly
16 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV at 27 hr APAP × AT, 5,008 ALT, 693 U/L
20-24 hr: hemodialysis AST, 1,450 U/L
93 hr:
ALT, 240 U/L AST, 84 U/L
15 Female Diabetes, history of self-harm - 18 hr: NAC 150 mg/kg IV then NAC 12.5 mg/kg/hr IV 18 hr: 89 μg/mL 22 hr: No outcomes documented
Decreased responsiveness, 26 hr: fomepizole 15 mg/kg IV APAP × AT, 1,602 ALT, 55 U/L
AST, 142 U/L
43 hr:
ALT, 36 U/L
AST, 37 U/L
16 Female Abdominal pain, vomiting APAP 15 tablets (1 day prior; unknown dose) 24 hr: NAC 150 mg/kg IV then NAC 12.5 mg/kg/hr IV 24 hr: 24 μg/mL 32 hr: Transaminases continued to rise despite NAC but were managed with fomepizole
32 hr: fomepizole 15 mg/kg IV APAP × AT, 97,488 ALT, 3,812 U/L Transaminases improved, and a full recovery was made
After fomepizole: vitamin K 10 mg IV and lactulose AST, 6,222
220 hr:
ALT, 284 U/L
AST, 32 U/L
64 Female AUD - Before admission: intubation 6 hr: 411.5 μg/mL 45 hr: AST, 1,103 U/L Transaminases started to improve without clinical signs of deterioration by hour 81
Unresponsive 5 hr: NAC 150 mg/kg IV then NAC 12.5 mg/kg/hr IV infusion APAP × AT, 83,268 52 hr: ALT 1,260 U/L
13 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV at 23 hr 81 hr:
AST, 160 U/L
ALT, 721 U/L
Kaiser et al. [22] (2021) (n=4) 30 Female Shock, multiorgan dysfunction, hypotension Acute APAP ingestion (timing unknown) Timing unknown: fomepizole 15 mg/kg IV ×1 dose 31 hr: APAP × AT, 31,020 - Improved after fomepizole infusion and survived to hospital discharge
46 Male Shock, multiorgan dysfunction, hypotension Repeated supratherapeutic APAP ingestion (timing unknown) Timing unknown: fomepizole 15 mg/kg IV ×1 dose Initial: APAP × AT, 90,252 - Improved after fomepizole infusion and survived to hospital discharge
44 Male Shock, multiorgan dysfunction, hypotension Repeated supratherapeutic APAP ingestion (timing unknown) Timing unknown: fomepizole 15 mg/kg IV ×1 dose Initial: APAP × AT, 231,763 - Improved after fomepizole infusion and survived to hospital discharge
54 Male Shock, multiorgan dysfunction, hypotension Chronic APAP ingestion (timing unknown) Timing unknown: fomepizole 15 mg/kg IV ×1 dose Initial: APAP × AT, 39,592 Improved after fomepizole infusion and survived to hospital discharge
Shah et al. [23] (2021) (n=2) 44 Female SUD - Admission: crystalloid 40 mL/kg IV 13 hr after admission: 108.1 μg/mL 3 Days after admission: ALT, >5,000 IU/L Shock developed during admission and required IV NAC
Altered mental status 19 hr after admission: NAC 140 mg/kg PO then 70 mg/kg PO every 4 hr, fomepizole 15 mg/kg IV AST, 8,372 IU/L Patient survived to discharge
3 Days after admission: NAC 150 mg/kg IV then 15 mg/kg/hr IV
56 Female Breast cancer, bipolar disorder, chronic pain syndrome - Admission: crystalloid 40 mL/kg IV 19 hr after initial labs: >300 μg/mL 4 Days after admission: ALT, 4,553 IU/L Patient survived to discharge
Altered mental status After crystalloid: NAC 150 mg/kg IV then 15 mg/kg/hr IV AST, 2,579 IU/L
19 hr after initial labs: fomepizole 15 mg/kg IV
Shah et al. [24] (2020) (n=3) 62 Female SIRS, lactic acidosis, arterial acidemia, Unknown dose (5 hr prior) Timing unknown: NAC, fomepizole (unknown dose) 5 hr: 1,014 μg/mL 5 hr: Survived to hospital discharge without liver transplant
APAP × AT, 521,202 ALT, 10 IU/L
AST, 13 IU/L
56 Female SIRS, lactic acidosis, arterial acidemia, - Timing unknown: crystalloid 40 mL/kg IV, NAC, fomepizole (unknown dose) Timing unknown: 298 μg/mL Timing unknown: ALT, 326 IU/L Survived to hospital discharge without liver transplant
APAP × AT, 97,148 AST, 245 IU/L
58 Female SIRS, lactic acidosis, arterial acidemia, - Timing unknown: crystalloid 4L IV, NAC, fomepizole (unknown dose) Timing unknown: 22.4 μg/mL Timing unknown: transaminases 3,466–11,001 IU/L Survived to hospital discharge without liver transplant
APAP × AT, 133,750
Rampon et al. [25] (2020) (n=6) 49 Female Depression APAP, benzodiazepines, other unknown coingestants (4 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 4 hr: 140.8 μg/mL (undetectable after hemodialysis) 62 hr: Persistently elevated APAP levels were seen despite NAC and fomepizole; hemodialysis started to address this
Encephalopathy, salicylates 45 mg/dL 6 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr ALT, 79 U/L No biochemical or clinical evidence of liver failure developed
36 hr: hemodialysis ×1 session AST, 51 U/L Therapy was well tolerated
110 hr:
ALT, 60 U/L
AST, 26 U/L
14 Female Encephalopathy, lethargy APAP, diphenhydramine (4 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5mg/kg/hr IV 6 hr: 251.6 μg/mL 4 hr: AST, 19 U/L Persistently elevated APAP levels were seen despite NAC; fomepizole was started to address this
6 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr 102 hr: ALT, 12 U/L No biochemical or clinical evidence of liver failure developed
Therapy was well tolerated
9 Male - - 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 4 hr: 281.7 μg/mL 20 hr: AST, 47 U/L Persistently elevated APAP levels were seen despite NAC; fomepizole was started to address this
6 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr 40 hr: ALT, 41 U/L No evidence of liver failure was observed
Therapy was well tolerated
15 Female Depression, prior suicide attempts APAP 50 g, unknown coingestants (2 hr prior) 2 hr: activated charcoal, NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 8.5 hr: 311.9 μg/mL 16 hr: Persistently elevated APAP levels were seen despite NAC; fomepizole was started to address this
Nausea, vomiting 8.5–9 hr: NAC increased to 18.75 mg/kg/hr IV, fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr ALT, 15 U/L No evidence of liver failure was observed
AST, 16 U/L Therapy was well tolerated
42 Female Nausea, lethargy, tachycardia APAP 100 g, ibuprofen 40 g, loperamide 400 mg (5 hr prior) 5 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 5 hr: 201.8 μg/mL 12 hr: Persistently elevated APAP levels were seen despite NAC; fomepizole was started to address this
6 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr ALT, 29 U/L No evidence of liver failure was observed
AST, 54 U/L Therapy was well tolerated
15 Female Nausea, RUQ pain, abdominal tenderness APAP 50–62.5 g (2 hr prior) 2 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV ×21 hr 4 hr: 361 μg/mL 13 hr: No evidence of hepatocellular injury or liver failure was observed
5.5 hr: fomepizole 15 mg/kg IV ALT, 19 U/L Therapy was well tolerated
AST, 10 U/L

APAP, acetaminophen; APAP × ATb), acetaminophen-aminotransferase multiplication product; NAC, N-acetylcysteine; IV, intravenous; CRRT, continuous renal replacement therapy; ALT, alanine transaminase; AST, aspartate transaminase; AKI, acute kidney injury; SUD, substance use disorder; ESRD, end-stage renal disease; COPD, chronic obstructive pulmonary disease; AUD, alcohol use disorder; PO, per oral; SIRS, systemic inflammatory response syndrome; RUQ, right upper quadrant; CKD, chronic kidney disease; ECG, electrocardiogram.

a)Hours after ingestion if known unless stated otherwise.

b)When the APAP nomogram cannot be used (i.e., when the time after ingestion is unknown), an APAP×AT multiplication product was calculated by multiplying APAP and ALT or AST levels (whichever is higher). A value above the threshold of 10,000 mg/L ×U/L suggests a potential risk of hepatotoxicity and the need to initiate therapy for APAP toxicity.

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The role of fomepizole in acetaminophen-related poisoning: a narrative review
Clin Exp Emerg Med. 2026;13(1):13-27.   Published online August 13, 2025
DOI: https://doi.org/10.15441/ceem.25.059
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The role of fomepizole in acetaminophen-related poisoning: a narrative review
Clin Exp Emerg Med. 2026;13(1):13-27.   Published online August 13, 2025
DOI: https://doi.org/10.15441/ceem.25.059
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The role of fomepizole in acetaminophen-related poisoning: a narrative review
Study Age (yr) Sex Medical history, presentation, timing Ingestion dose and timing (if known) Intervention and timing of interventions after ingestion unless stated otherwise (if known) Laboratory findinga)
 Clinical course
APAP level Liver enzyme level
Williams et al. [3] (2024) 18 Male Depression, anxiety, borderline personality disorder APAP 125 g (1 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV ×3 days  At 4 hr: 738 μg/mL (undetectable at 57 hr) Day 2: AST, 50 U/L Developed shock, decline in mental status, acidosis at 5 hr
Nausea, vomiting 5 hr: intubation, norepinephrine, vasopressin Day 4: ALT, 55 U/L Mental status, liver enzymes returned to baseline on day 3, and no permanent liver toxicities developed
9 hr: fomepizole 15 mg/kg IV, hemodialysis for 4 hr ×3 days
16 hr: CRRT for 4 hr, NAC 70 mg/kg PO every 4 hr, fomepizole decreased to 10 mg/kg IV every 6 hr
Chary et al. [4] (2023) 50 Female SUD - Preadmission: naloxone 4 mg IN and 2 mg IV  Days 1–3: 200 to >530 μg/mL (<100 μg/mL on day 5) Days 3–4: Patient developed grade III encephalopathy and started CRRT on day 5
Unresponsiveness, somnolence, ethanol 293 mg/dL Admission: NAC 150 mg/kg IV, then 12.5 mg/kg/hr IV for 4 hr, then 6.25 mg/kg/hr IV for 16 hr AST, >6,000 U/L (normalized on day 5) Developed neutropenia, and filgrastim was started on day 6
After NAC: intubation ALT, 6,600 U/L Mental status improved by day 7 and returned to baseline by day 10
Day 4: fomepizole 15 mg/kg IV and cryoprecipitate 6 U 12 hr after
Day 5: fomepizole 10 mg/kg IV, CRRT
Day 6: filgrastim 300 μg
Lobo et al. [5] (2023) 59 Male Encephalopathy APAP 100 g, ibuprofen 100 g (5 hr prior) Timing unknown: NAC, fomepizole 15 mg/kg IV  At 24 hr: 535 μg/mL (undetectable at 105 hr) Timing unknown: Patient discharged on day 25
After transfer to tertiary facility: NAC 12.5 mg/kg/hr IV, fomepizole 10 mg/kg IV ×5 doses ALT, 123 U/L (normalized at 97 hr)
31 hr: CRRT ×24 hr AST, 100 U/L (normalized at 5 hr)
Pepin et al. [6] (2023) 7 mo Female Fever, vomiting, cough, encephalopathy APAP 4.8 g, ibuprofen (over 5 days) Timing unknown: NAC 150 mg/kg IV over 1 hr, then 50 mg/kg IV over 4 hr, then 100 mg/kg IV over 16 hr  Timing unknown: 239.6 μg/mL (1 μg/mL on day 5) 8 hr after admission: AST, >27,300 U/L (216 U/L on day 6) Worsening agitation observed on day 4
8 hr after admission: fomepizole 15 mg/kg IV ALT, >11,700 U/L (2,403 U/L on day 6) NAC was stopped on day 4, and patient returned to mental baseline on day 5 and was discharged on day 8
After fomepizole: fresh frozen plasma, platelets, aminocaproic acid 500 mg, vitamin K 3 mg IV
After transfer to transplant facility: fomepizole 10 mg/kg IV every 12 hr ×3 doses, NAC 12.5 mg/kg/hr IV ×81 hr
Ho and Brambl [7] (2023) 37 Male Tachycardia, hypothermia, tachypnoea, hypertension, acidemia, hepatotoxicity, possible alcohol ingestion - Timing unknown intubation, activated charcoal 50 g, NAC 140 mg/kg PO, NAC 150 mg/kg IV then 24 mg/kg/hr IV, fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr ×4 doses  On admission: 707 μg/mL (undetectable on day 3) Day 2: transaminases, >3,000 U/L Despite fomepizole, charcoal, NAC, and hemodialysis, patient continued to be acidotic and developed significant hepatotoxicity
12 hr after admission: hemodialysis Other outcomes were not documented
Kusnik et al. [8] (2022) 58 Female Fibromyalgia, AUD Unknown quantity (6–18 hr prior) 6–18 hr: NAC ×21 hr, multivitamins, pantoprazole  On 6–18 hr: 126.3 μg/mL (undetectable at 40 hr) Days after 27 hr: Kidney function improved 80 hr after admission without hemodialysis
Altered mental status, abdominal pain ×2 days, AKI 15–27 hr: NAC increased to 12.5 mg/kg/hr IV, then decreased to 6.25 mg/kg/hr IV after APAP undetectable AST, 34,665–13,995 U/L (normalized ≈4 wk after admission) Encephalopathy improved 1 day after admission
36–48 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr given at 30, 45, 57, 69, and 81 hr Liver and kidney function returned to baseline 4 wk after admission
Timing unknown: albumin, midodrine, octreotide
Bassi et al. [9] (2022) 23 Male Agitation, laryngospasms APAP 188.5 g, naproxen, ibuprofen, hydrocodone, loratadine (1–3 hr prior) Admission: NAC 200 mg/kg IV over 4 hr, then 100 mg/kg IV over 16 hr, activated charcoal 50g 20 hr after admission: 287 μg/mL (undetectable at 96 hr) AST (timing unknown): 209 and 298 U/L Recovered without liver transplant
34 hr: NAC infusion rate doubled, fomepizole 15 mg/kg IV, activated charcoal 50g
47 hr: endoscopy
Before transfer to transplant facility: CRRT
Dion et al. [10] (2022) 17 Male Undiagnosed eating disorder APAP 50–75 g, caffeinated drink, sennosides (2 hr prior) 3 hr: NAC 300 mg/kg IV, fomepizole 15 mg/kg IV  At 12 hr: 391.8 μg/mL (2.8 μg/mL at 60 hr) No significant increases in liver enzymes were observed Abdominal pain resolved by day 3, and patient was cleared for discharge on day 4
Abdominal pain, altered mental status, apnea Day 2: fomepizole 15 mg/kg IV, NAC 300 mg/kg IV ×48 hr
Chiu et al. [11] (2021) 20 Female Anxiety, self-harm/prior suicide attempts APAP >120 g, ibuprofen 65 g, oxycodone 300 mg (2 hr prior) Timing unknown: intubation, norepinephrine 0.3 μg/kg/min ×2 days, epinephrine 0.2 μg/kg/min ×2 days, sodium bicarbonate  At 7 hr: ≈680 μg/mL (undetectable at 32 hr) Admission day 2: ALT 76 U/L 24 hr after admission, patient was awake and oriented and followed commands
Tachycardia, refractory shock, altered LOC, metabolic acidosis 3 hr: activated charcoal, NAC 150 mg/kg IV then 15 mg/kg/hr IV ×3 days, fomepizole 1,000 mg IV (10 mg/kg IV every 4 hr during dialysis and for an additional day 700 mg IV every 12 hr; total 2 days of fomepizole) Metabolic acidosis was refractory to NAC and fomepizole, requiring dialysis
6 hr: hemodialysis Acid-base/hemodynamic status returned to baseline without organ failure
Homan et al. [12] (2021) 58 Female AUD, hypertension, hyperlipidemia, hepatic steatosis - Timing unknown: fluids, NAC, fomepizole (unknown dose), lactulose, rifaximin, vitamin K, albumin, octreotide, midodrine  Unknown timing: 58.3 (units unknown) Unknown timing: AST, 19,816 Pancreatitis, coagulopathy, and hepatorenal syndrome developed
Abdominal pain, nausea, vomiting, lethargy, encephalopathy, RUQ tenderness ALT, 5,544 (units unknown) Mental status and laboratory abnormalities improved gradually, and APAP levels became undetectable
Cuninghame et al. [13] (2021) 24 Female Endometriosis, chronic pelvic pain, depression, anxiety, previous suicide attempts APAP 50 g, gabapentin 25.5 g, morphine 60 mg (16 hr prior) 16 hr: NAC 60 mg/kg IV then 12 mg/kg/hr IV, fomepizole 600 mg IV q6 hr  18 hr: 602 μg/mL (undetectable on admission day 8) 88 hr: transaminases >8,000 U/L Fulminant liver failure progressed with cerebral edema, encephalopathy, hypoglycemia, petechial hemorrhage, diffuse axonal injury, coagulopathy
Altered mental status, metabolic acidosis 18 hr: intubation Altered mental status and metabolic acidosis were refractory to all interventions
43 hr: hemodialysis First case report of fatal APAP ingestion refractory to both hemodialysis and CRRT at time of writing
56 hr: second hemodialysis run
66 hr: CRRT
48 hr after CRRT: whole bowel irrigation, colonic decompression
16 days after admission: life-sustaining measures withdrawn
Woolum et al. [14] (2020) 55 M with Male Type I bipolar depressive disorder, previous suicidal ideation, diabetes, CKD stage III APAP 65 g (7 hr prior) Before admission: naloxone 1.5 mg IV  At 7 hr: 883 μg/mL (undetectable on admission day 3) Admission day 2: AST, 1,791 U/L Patient was discharged after 4 days of hospitalization without systemic, hepatic, or mental abnormalities
Unresponsive Admission: intubation, NAC 6.25 mg/kg/hr IV, sodium bicarbonate, fomepizole 15 mg/kg IV ALT, 743 U/L (normalized ≈4 days after admission)
3 hr after admission: hemodialysis ×3 hr, NAC increased to 18.75 mg/kg/hr IV ×3 days
Link et al. [15] (2020) 45 Male - - 4 hr after admission: NAC 150 mg/kg IV, then 12.5 mg/kg/hr IV, then 18.75 mg/kg/hr IV at 8 hr (stopped at 35 hr), fomepizole 15 mg/kg IV, then 15 mg/kg IV at 16 hr, then 10 mg/kg IV at 28 hr  4 hr after admission: 791 μg/mL (<74.5 μg/mL at 28 hr after admission) ALT remained WNL No liver injuries were sustained, and liver enzymes, neurocognition returned to baseline on day 8
8 hr after admission: CRRT until 23 hr
Hidalgo et al. [16] (2020) 18 Female Lethargy APAP 46 g (10 hr prior) 10 hr: NAC IV  At 10 hr: > 250 μg/mL (undetectable 18 hr after dialysis) At 58 hr: Discharged after 6 days without issues
After NAC: fomepizole 15 mg/kg IV, hemodialysis ×4 hr AST, 3,820 IU/L
After dialysis: fomepizole 10 mg/kg IV ALT, 4,346 IU/L
After second dose of fomepizole: CRRT (normalized at unknown time)
Shah and Beuhler [17] (2020) 33 Male AUD APAP 25 g (taken over past 2 days) 9 hr after admission: NAC 150 mg/kg IV, then 12 mg/kg/hr IV ×4 hr, then 6.25 mg/kg/hr IV ×9 hr  Admission: 337 μg/mL (20 μg/mL at 42 hr) Admission day 3: Patient was medically cleared and did well
Abdominal pain, tachycardia, tachypnea 11 hr after admission: fomepizole 15 mg/kg IV AST, 198 U/L
ALT, 301 U/L
Kiernan et al. [18] (2019) 64 Female Comatose, anion gap metabolic acidosis, lactatemia APAP 104 g, diphenhydramine 5.2 g (3 hr prior) 3 hr: intubation, epinephrine 100 μg IV, dopamine 10 μg/kg/min IV then 15 μg/kg/min IV, norepinephrine 10 μg/min IV  At 3 hr: 1,017 μg/mL (< 15 μg/mL at 48 hr) At 3 hr: Complete resolution of metabolic acidosis and coma without hepatitis or sequelae, discharged 8 days after admission
After initial therapy: sodium bicarbonate IV AST, 21 IU/L;
2 hr after first APAP level: NAC 200 mg/kg IV during dialysis 300 mg/kg IV at 15 hr and 100 mg/kg IV at 16 hr ALT, 99 IU/L
7 hr after first APAP level: fomepizole 15 mg/kg IV then 10 mg/kg IV at 15 hr
10 hr after first APAP level: hemodialysis ×6 hr
Villano et al. [19] (2015) 28 Male Depressed LOC, unresponsiveness, tachycardia, tachypnea, acidemia Unknown dose (16 hr prior) Timing unknown: fomepizole (unknown dose), NAC ×45 hr  At 16 hr: 616 μg/mL At 16 hr: ALT, 27 U/L Recovery was made without hemodialysis
After initial labs: AST, 67 U/L
Zell-Kanter et al. [20] (2013) 59- Female Depression - Timing unknown: intubation, activated charcoal 1/kg, sodium bicarbonate 1–2 mEq/kg, NAC ×59 hr, naloxone, fomepizole ×1 dose (unknown dose)  Several hours after initial readings: 1,193 mg/L Admission day 2: Patient treated successfully by admission day 4
Obtunded, agonal respirations AST, 3,150 U/L
ALT, 2,780 U/L (normalized on admission day 4)
Study Age (yr) Sex Medical history and presentation Ingestion dose and timing (if known) Timing of interventions after ingestion unless stated otherwise (if known) Laboratory findinga)
 Clinical course
APAP level and APAP × AT Liver enzyme level
Link et al. [21] (2022) (n=7) 47 Female Lightheadedness, confusion, hypoglycemia APAP 1 g every 4 hr ×2–3 days (12 hr prior) 16 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 16 hr: 10.8 μg/mL 29 hr: ALT, 3,325 U/L (118 U/L at 258 hr) AKI developed during hospitalization and was managed with CRRT
Several hours after NAC: intubation, norepinephrine, vasopressin, angiotensin II APAP × AT, 26,322 41 hr: AST, 9,305 U/L (77 U/L at 258 hr) Patient developed hypotension requiring vasopressors
After intubation/vasopressors: CRRT A full recovery was made, and no liver failure was observed at discharge
24 hr: fomepizole 15 mg/kg IV ×4 doses at 24, 36, 57, 70 hr
43 Female HIV, SUD, depression, epilepsy APAP 5 g (12 hr prior) 19 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 19 hr: 18 μg/mL 30 hr: A full and rapid recovery was made, and the patient was discharged without new impairments
Hemorrhoidal pain 31 hr: fomepizole 15 mg/kg IV APAP × AT, 50,620 ALT, 3,555 U/L Transaminases recovered quickly
AST, 12,655 U/L
114 hr:
ALT, 382 U/L
AST, 64 U/L
18 Female APAP 25 g, diphenhydramine 300–600 mg (4 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg IV 4 hr: 159 μg/mL 4 hr: 159 μg/mL No significant liver injury occurred
8 hr: fomepizole 15 mg/kg IV ×2 doses at 8 and 21 hr APAP × AT, 2,560
51 Female ESRD, diabetes, COPD, depression, intimate partner violence APAP 6.5–9.75 g (4 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 4 hr: 313 μg/mL 18 hr: Transaminases improved quickly
16 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV at 27 hr APAP × AT, 5,008 ALT, 693 U/L
20-24 hr: hemodialysis AST, 1,450 U/L
93 hr:
ALT, 240 U/L AST, 84 U/L
15 Female Diabetes, history of self-harm - 18 hr: NAC 150 mg/kg IV then NAC 12.5 mg/kg/hr IV 18 hr: 89 μg/mL 22 hr: No outcomes documented
Decreased responsiveness, 26 hr: fomepizole 15 mg/kg IV APAP × AT, 1,602 ALT, 55 U/L
AST, 142 U/L
43 hr:
ALT, 36 U/L
AST, 37 U/L
16 Female Abdominal pain, vomiting APAP 15 tablets (1 day prior; unknown dose) 24 hr: NAC 150 mg/kg IV then NAC 12.5 mg/kg/hr IV 24 hr: 24 μg/mL 32 hr: Transaminases continued to rise despite NAC but were managed with fomepizole
32 hr: fomepizole 15 mg/kg IV APAP × AT, 97,488 ALT, 3,812 U/L Transaminases improved, and a full recovery was made
After fomepizole: vitamin K 10 mg IV and lactulose AST, 6,222
220 hr:
ALT, 284 U/L
AST, 32 U/L
64 Female AUD - Before admission: intubation 6 hr: 411.5 μg/mL 45 hr: AST, 1,103 U/L Transaminases started to improve without clinical signs of deterioration by hour 81
Unresponsive 5 hr: NAC 150 mg/kg IV then NAC 12.5 mg/kg/hr IV infusion APAP × AT, 83,268 52 hr: ALT 1,260 U/L
13 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV at 23 hr 81 hr:
AST, 160 U/L
ALT, 721 U/L
Kaiser et al. [22] (2021) (n=4) 30 Female Shock, multiorgan dysfunction, hypotension Acute APAP ingestion (timing unknown) Timing unknown: fomepizole 15 mg/kg IV ×1 dose 31 hr: APAP × AT, 31,020 - Improved after fomepizole infusion and survived to hospital discharge
46 Male Shock, multiorgan dysfunction, hypotension Repeated supratherapeutic APAP ingestion (timing unknown) Timing unknown: fomepizole 15 mg/kg IV ×1 dose Initial: APAP × AT, 90,252 - Improved after fomepizole infusion and survived to hospital discharge
44 Male Shock, multiorgan dysfunction, hypotension Repeated supratherapeutic APAP ingestion (timing unknown) Timing unknown: fomepizole 15 mg/kg IV ×1 dose Initial: APAP × AT, 231,763 - Improved after fomepizole infusion and survived to hospital discharge
54 Male Shock, multiorgan dysfunction, hypotension Chronic APAP ingestion (timing unknown) Timing unknown: fomepizole 15 mg/kg IV ×1 dose Initial: APAP × AT, 39,592 Improved after fomepizole infusion and survived to hospital discharge
Shah et al. [23] (2021) (n=2) 44 Female SUD - Admission: crystalloid 40 mL/kg IV 13 hr after admission: 108.1 μg/mL 3 Days after admission: ALT, >5,000 IU/L Shock developed during admission and required IV NAC
Altered mental status 19 hr after admission: NAC 140 mg/kg PO then 70 mg/kg PO every 4 hr, fomepizole 15 mg/kg IV AST, 8,372 IU/L Patient survived to discharge
3 Days after admission: NAC 150 mg/kg IV then 15 mg/kg/hr IV
56 Female Breast cancer, bipolar disorder, chronic pain syndrome - Admission: crystalloid 40 mL/kg IV 19 hr after initial labs: >300 μg/mL 4 Days after admission: ALT, 4,553 IU/L Patient survived to discharge
Altered mental status After crystalloid: NAC 150 mg/kg IV then 15 mg/kg/hr IV AST, 2,579 IU/L
19 hr after initial labs: fomepizole 15 mg/kg IV
Shah et al. [24] (2020) (n=3) 62 Female SIRS, lactic acidosis, arterial acidemia, Unknown dose (5 hr prior) Timing unknown: NAC, fomepizole (unknown dose) 5 hr: 1,014 μg/mL 5 hr: Survived to hospital discharge without liver transplant
APAP × AT, 521,202 ALT, 10 IU/L
AST, 13 IU/L
56 Female SIRS, lactic acidosis, arterial acidemia, - Timing unknown: crystalloid 40 mL/kg IV, NAC, fomepizole (unknown dose) Timing unknown: 298 μg/mL Timing unknown: ALT, 326 IU/L Survived to hospital discharge without liver transplant
APAP × AT, 97,148 AST, 245 IU/L
58 Female SIRS, lactic acidosis, arterial acidemia, - Timing unknown: crystalloid 4L IV, NAC, fomepizole (unknown dose) Timing unknown: 22.4 μg/mL Timing unknown: transaminases 3,466–11,001 IU/L Survived to hospital discharge without liver transplant
APAP × AT, 133,750
Rampon et al. [25] (2020) (n=6) 49 Female Depression APAP, benzodiazepines, other unknown coingestants (4 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 4 hr: 140.8 μg/mL (undetectable after hemodialysis) 62 hr: Persistently elevated APAP levels were seen despite NAC and fomepizole; hemodialysis started to address this
Encephalopathy, salicylates 45 mg/dL 6 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr ALT, 79 U/L No biochemical or clinical evidence of liver failure developed
36 hr: hemodialysis ×1 session AST, 51 U/L Therapy was well tolerated
110 hr:
ALT, 60 U/L
AST, 26 U/L
14 Female Encephalopathy, lethargy APAP, diphenhydramine (4 hr prior) 4 hr: NAC 150 mg/kg IV then 12.5mg/kg/hr IV 6 hr: 251.6 μg/mL 4 hr: AST, 19 U/L Persistently elevated APAP levels were seen despite NAC; fomepizole was started to address this
6 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr 102 hr: ALT, 12 U/L No biochemical or clinical evidence of liver failure developed
Therapy was well tolerated
9 Male - - 4 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 4 hr: 281.7 μg/mL 20 hr: AST, 47 U/L Persistently elevated APAP levels were seen despite NAC; fomepizole was started to address this
6 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr 40 hr: ALT, 41 U/L No evidence of liver failure was observed
Therapy was well tolerated
15 Female Depression, prior suicide attempts APAP 50 g, unknown coingestants (2 hr prior) 2 hr: activated charcoal, NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 8.5 hr: 311.9 μg/mL 16 hr: Persistently elevated APAP levels were seen despite NAC; fomepizole was started to address this
Nausea, vomiting 8.5–9 hr: NAC increased to 18.75 mg/kg/hr IV, fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr ALT, 15 U/L No evidence of liver failure was observed
AST, 16 U/L Therapy was well tolerated
42 Female Nausea, lethargy, tachycardia APAP 100 g, ibuprofen 40 g, loperamide 400 mg (5 hr prior) 5 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV 5 hr: 201.8 μg/mL 12 hr: Persistently elevated APAP levels were seen despite NAC; fomepizole was started to address this
6 hr: fomepizole 15 mg/kg IV then 10 mg/kg IV every 12 hr ALT, 29 U/L No evidence of liver failure was observed
AST, 54 U/L Therapy was well tolerated
15 Female Nausea, RUQ pain, abdominal tenderness APAP 50–62.5 g (2 hr prior) 2 hr: NAC 150 mg/kg IV then 12.5 mg/kg/hr IV ×21 hr 4 hr: 361 μg/mL 13 hr: No evidence of hepatocellular injury or liver failure was observed
5.5 hr: fomepizole 15 mg/kg IV ALT, 19 U/L Therapy was well tolerated
AST, 10 U/L
Table 1. Summary of included case reports about fomepizole use in acetaminophen overdose

APAP, acetaminophen; NAC, N-acetylcysteine; IV, intravenous; CRRT, continuous renal replacement therapy; PO, per oral; AST, aspartate transaminase; ALT, alanine transaminase; SUD, substance use disorder; IN, intranasal; AUD, alcohol use disorder; AKI, acute kidney injury; LOC, loss of consciousness; RUQ, right upper quadrant; CKD, chronic kidney disease; WNL, within normal limits.

Highest reported level.

Table 2. Summary of included case series about fomepizole use in acetaminophen overdose

APAP, acetaminophen; APAP × ATb), acetaminophen-aminotransferase multiplication product; NAC, N-acetylcysteine; IV, intravenous; CRRT, continuous renal replacement therapy; ALT, alanine transaminase; AST, aspartate transaminase; AKI, acute kidney injury; SUD, substance use disorder; ESRD, end-stage renal disease; COPD, chronic obstructive pulmonary disease; AUD, alcohol use disorder; PO, per oral; SIRS, systemic inflammatory response syndrome; RUQ, right upper quadrant; CKD, chronic kidney disease; ECG, electrocardiogram.

Hours after ingestion if known unless stated otherwise.

When the APAP nomogram cannot be used (i.e., when the time after ingestion is unknown), an APAP×AT multiplication product was calculated by multiplying APAP and ALT or AST levels (whichever is higher). A value above the threshold of 10,000 mg/L ×U/L suggests a potential risk of hepatotoxicity and the need to initiate therapy for APAP toxicity.

Table 1.

Table 2.

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