Hyperammonemia secondary to asparaginase: A case series

Nussbaum, Vicki M; Lubcke, Nicole; Findlay, Russell

doi:10.1177/1078155214551590

Cited by 38 publications

(33 citation statements)

References 14 publications

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“…In cats, significant increases in plasma ammonia concentration have been shown to occur at both 2 and 7 days after L‐asp therapy with no clinical implications . Recent literature in people suggests that increased plasma ammonia concentration after L‐asp may be more common than previously suspected, especially with the pegylated form . In the current study, plasma ammonia concentrations were statistically significantly increased at both 16 and 48 hours post L‐asp administration.…”

Section: Discussionsupporting

confidence: 39%

Plasma ammonia concentration after L‐asparaginase therapy in 27 dogs with high‐grade lymphoma or leukemia

Speas

Lyles

Wirth

et al. 2018

J Vet Emergen Crit Care

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Section: Discussionsupporting

confidence: 39%

Plasma ammonia concentration after L‐asparaginase therapy in 27 dogs with high‐grade lymphoma or leukemia

Speas

Lyles

Wirth

et al. 2018

J Vet Emergen Crit Care

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“…[82] Asparaginase therapy has also been associated with nonantibody-mediated infusion reactions that may result from spikes in serum ammonia levels. [83][84][85][86] Ammonia accumulation occurs as asparaginase facilitates the rapid conversion of asparagine and glutamine to aspartic acid and glutamic acid, with ammonia as the shared by-product of both reactions. [10] Symptoms of hyperammonemia are often transient in nature and can include nausea, vomiting, headache, dizziness, and rash.…”

Section: Infusion-related Adverse Eventsmentioning

confidence: 99%

“…Of note, patients with metabolic disorders who experience hyperammonemia due to defects in their ammonia metabolism, are treated with agents such as Larginine, metformin, lactulose, or sodium phenylacetate/sodium benzoate to lower elevated ammonia levels. [85,98] Consideration can be given to using the same agents in patients with evidence of encephalopathic changes due to hyperammonemia.…”

Section: Differentiation Of Hypersensitivity and Infusion Reactionsmentioning

confidence: 99%

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

Burke

Rheingold

2016

Leukemia & Lymphoma

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Asparaginase is a key component of therapy for acute lymphoblastic leukemia (ALL). Traditionally, asparaginase was administered intramuscularly but is now commonly given intravenously. Although intravenous administration is less painful, it can be challenging to differentiate hypersensitivity versus infusion-related reactions. The ability to distinguish between asparaginase-mediated reactions is critical to ensure optimal asparaginase treatment. In this paper, we will review the differences in pharmacokinetics and toxicities, when asparaginase is administered intravenously versus intramuscularly in pediatric patients with ALL. Differences between antibody-mediated hypersensitivity events and nonantibody-mediated infusion reactions will be addressed to assist practitioners in distinguishing between these clinically similar asparaginase-associated toxicities.ARTICLE HISTORY

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“…The occurrence of these reactions with the first dose of IV PEG is further support of a nonantibody‐mediated mechanism. It is possible that PEG‐induced acute hyperammonemia may mediate at least some of the symptoms and signs associated with these nonallergic infusion reactions …”

Section: Introductionmentioning

confidence: 99%

Universal premedication and therapeutic drug monitoring for asparaginase‐based therapy prevents infusion‐associated acute adverse events and drug substitutions

Cooper¹,

Young²,

Bowen³

et al. 2019

Pediatric Blood & Cancer

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Background Asparaginase is a critical component of lymphoblastic leukemia therapy, with intravenous pegaspargase (PEG) as the current standard product. Acute adverse events (aAEs) during PEG infusion are difficult to interpret, representing a mix of drug‐inactivating hypersensitivity and noninactivating reactions. Asparaginase Erwinia chrysanthemi (ERW) is approved for PEG hypersensitivity, but is less convenient, more expensive, and yields lower serum asparaginase activity (SAA). We began a policy of universal premedication and SAA testing for PEG, hypothesizing this would reduce aAEs and unnecessary drug substitutions. Procedure Retrospective chart review of patients receiving asparaginase before and after universal premedication before PEG was conducted, with SAA performed 1 week later. We excluded patients who had nonallergic asparaginase AEs. Primary end point was substitution to ERW. Secondary end points included aAEs, SAA testing, and cost. Results We substituted to ERW in 21 of 122 (17.2%) patients pre‐policy, and 5 of 68 (7.4%) post‐policy (RR, 0.427; 95% CI, 0.27–0.69, P = 0.028). All completed doses of PEG yielded excellent SAA (mean, 0.90 units/mL), compared with ERW (mean, 0.15 units/mL). PEG inactivation post‐policy was seen in 2 of 68 (2.9%), one silent and one with breakthrough aAE. The rate of aAEs pre/post‐policy was 17.2% versus 5.9% (RR, 0.342; 95% CI, 0.20–0.58, P = 0.017). Grade 4 aAE rate pre/post‐policy was 15% versus 0%. Cost analysis predicts $125 779 drug savings alone per substitution prevented ($12 402/premedicated patient). Conclusions Universal premedication reduced substitutions to ERW and aAE rate. SAA testing demonstrated low rates of silent inactivation, and higher SAA for PEG. A substantial savings was achieved. We propose universal premedication for PEG be standard of care.

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Hyperammonemia secondary to asparaginase: A case series

Cited by 38 publications

References 14 publications

Plasma ammonia concentration after L‐asparaginase therapy in 27 dogs with high‐grade lymphoma or leukemia

Plasma ammonia concentration after L‐asparaginase therapy in 27 dogs with high‐grade lymphoma or leukemia

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

Universal premedication and therapeutic drug monitoring for asparaginase‐based therapy prevents infusion‐associated acute adverse events and drug substitutions

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