sodium phenylacetate/sodium benzoate / Generic mfg. - LARVOL DELTA

FATAL REYE SYNDROME: REVISITING THE RARE DISEASE (SCCM 2025) - "Public health campaign against aspirin use in children significantly decreased Reye syndrome's incidence, while concomitantly reducing pediatricians' clinical experience with the disease. Description: A 2-year-old typically developing male with immune thrombocytopenic purpura on escalating doses of eltrombopag and unilateral renal agenesis presented to ED with 2 days of vomiting and 1 day of lethargy...Hyperammonemia was initially refractory to management with an Ammonul infusion and continuous veno-venous hemodiafiltration...With clinician lack of exposure to Reye syndrome in recent decades, it may be under recognized and under reported. This case calls for efforts to characterize the current incidence of Reye syndrome and better understand risk factors beyond the classic salicylate exposure and disorders of metabolism."

CNS Disorders • Hematological Disorders • Hepatology • Immune Thrombocytopenic Purpura • Infectious Disease • Liver Failure • Metabolic Disorders • Pediatrics • Rare Diseases • Thrombocytopenic Purpura

Acquired Hyperammonemia and L-carnitine Deficiency Mimicking Urea Cycle Disorder (AAN 2024) - "We present a case of nutritionally driven acquired urea cycle disorder with carnitine deficiency leading to severe hyperammonemia, encephalopathy and extensive MRI changes—all resolved completely with correction of underlying essential amino acid deficiency. It is important to find the etiology of underlying metabolic derangements and should treat and prognosticate accordingly."

CNS Disorders • Epilepsy • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Pancreatitis

A case of Ornithine Transcarbamylase Deficiency (ACMG 2024) - "Ammonia levels were measured, initially reading 1228 mmol/l and subsequently rising to greater than 1500 mmol/l, despite efforts to lower them with Aquadex therapy and ammonia scavengers (arginine and ammonul [sodium benzoate and sodium phenylbutarate])... While the variant (c.238A>G, p.K80E) exhibited a considerably milder clinical presentation in the female patient, it manifested as a markedly more severe phenotype in our male patient, with early and aggressive onset. Another crucial point to consider is that in cases where patients exhibit a substantial increase in ammonia levels, the RRT approach to be employed is CVVH as the use of Aquadex alone has proven insufficient for effectively eliminating excess ammonia."

Clinical • Acute Kidney Injury • CNS Disorders • Epilepsy • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Disease

Severe Hyperammonemia and Coma in a Post-partum Patient Secondary to a Urea Cycle Disorder (ATS 2023) - "RRT was later discontinued after initiating IV ammonia scavenger therapy with Ammonul (sodium phenylacetate and sodium benzoate)... Awareness of late-onset UCD in MICU patients as a cause of encephalopathy and hyperammonemia is necessary for early diagnosis and timely management to prevent life-threatening complications of hyperammonemia."

Clinical • Acute Kidney Injury • CNS Disorders • Critical care • Genetic Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease

Pharmacokinetics, safety, and tolerability of sodium phenylacetate and sodium benzoate in healthy Japanese volunteers: A phase I, single-center, open-label study. (PubMed, Drug Metab Pharmacokinet) - "Urinary excretion ratios of PAG and HIP at 48 h after the administration were 99.3% and 104%, respectively, suggesting that almost all NaPA and NaBZ were metabolized and excreted into urine. Overall, TAK-123 was well-tolerated in healthy Japanese adults."

Journal • PK/PD data • Metabolic Disorders

Compound heterozygote variants: c.848A > G; p.Glu283Gly and c.890C > T; p.Ala297Val, of Isovaleric acid-CoA dehydrogenase (IVD) gene causing severe Isovaleric acidemia with hyperammonemia. (PubMed, Mol Genet Metab Rep) - "However, the patient suffered from bone marrow suppression associated with the organic acidemia and required frequent platelet transfusions, as well as G-CSF for neutropenia. The management of this patient provides supporting evidence of the many theoretic metabolic "facts" including why Ammonul is not helpful in organic acidemias."

Journal • Hematological Disorders • Infectious Disease • Neutropenia • Novel Coronavirus Disease • CSF3

Budget Impact Analysis for the Use of Sodium Phenylacetate and Sodium Benzoate in the Treatment of Acute Hyperammonemia: Experience in a Saudi Setting (ISPOR 2022) - "Objectives: Sodium phenylacetate/Sodium benzoate injection combination is an orphan drug indicated as an adjunct therapy in treating acute Hyperammonemia and associated encephalopathy in patients with urea cycle enzyme deficiencies... For the analysis population, the use of Sodium phenylacetate/Sodium benzoate is associated with substantially increased costs. Considering the analysis findings, lack of robust evidence for survival benefits, and limited treatment options, Sodium phenylacetate/Sodium benzoate may be occasionally considered in cases not responsive or eligible for hemodialysis. Further clinical studies on this medication use are recommended."

HEOR • CNS Disorders • Pediatrics

HYPERAMMONEMIA IN FIBROLAMELLAR HEPATOCARCINOMA. (WSMRF 2022) - "She was experiencing persistent hyperammonemia ranging from 200?250 umol/L despite CRRT, so she was treated with intravenous arginine and Ammonul (sodium phenylacetate and sodium benzoate)...Other medication options, including lactulose, rifaximin, and other oral medications were not able to be given due to her ongoing GI bleed...ODC in turn catalyzes the decarboxylation of ornithine in polyamine synthesis, shunting ornithine away from the urea cycle and inhibiting OTC activity. In order to investigate this proposed mechanism, we intend to conduct further studies to measure polyamine synthesis, a downstream effect of the aforementioned mechanism."

Acute Kidney Injury • Cardiovascular • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Hepatology • Liver Failure • Nephrology • Oncology • Pediatrics • Renal Disease • Thrombosis • Venous Thromboembolism • AURKA • MYC

Continuous Renal Replacement Therapy for Two Neonates With Hyperammonemia. (PubMed, Front Pediatr) - "Continuous renal replacement therapy was more effective than scavenger therapy alone (Ammonul™) for rapid removal of ammonia in low weight infants (as low as 2.5 kg). Continuous renal replacement therapy is technically feasible in low weight infants with severe hyperammonemia secondary to an inborn error of metabolism."

Journal • Review • Genetic Disorders • Metabolic Disorders • Ophthalmology • Pediatrics

Peripheral venous route for administration of ammonul infusion for treatment of acute hyperammonemia. An experience from a tertiary center in Saudi Arabia. (PubMed, Saudi Med J) - "This data indicate that the use of Ammonul through a peripheral venous route appears to be safe and not associated with infusion-related local adverse effects."

Journal • Complement-mediated Rare Disorders • Hepatology • Metabolic Disorders • Thermal Injury

[VIRTUAL] A Rare Case of Late Onset Ornithine Transcarbamylase Deficiency Causing Acute Metabolic Encephalopathy (ATS-I 2020) - "He was started on valproic acid and escitalopram in the Emergency Department (ED), but deteriorated quickly with development of vomiting, hypotension, worsening mental status, and status epilepticus...The patient's exposure to Depakote may have precipitated hyperammonemia triggering acute decompensation of his underlying disease and eventual death...Currently, there are 3 FDA approved medications, namely Buphenyl (sodium phenylbutyrate), Ravicti (glycerol phenylgutyrate), and Ammonul (sodium phenylacetate and sodium benzoate). This case highlights a number of interesting points regarding identification and triggers of OTC deficiency."

Clinical • Ataxia • CNS Disorders • Epilepsy • Hypotension • Metabolic Disorders • Movement Disorders • Psychiatry • Schizophrenia

A Rare Case of Late Onset Ornithine Transcarbamylase Deficiency Causing Acute Metabolic Encephalopathy (ATS 2020) - "He was started on valproic acid and escitalopram in the Emergency Department (ED), but deteriorated quickly with development of vomiting, hypotension, worsening mental status, and status epilepticus...The patient’s exposure to Depakote may have precipitated hyperammonemia triggering acute decompensation of his underlying disease and eventual death...Treatment options for patients with OTC deficiency are relatively limited and include dietary modifications and ammonia-lowering medications. Currently, there are 3 FDA approved medications, namely Buphenyl (sodium phenylbutyrate), Ravicti (glycerol phenylgutyrate), and Ammonul (sodium phenylacetate and sodium benzoate).This case highlights a number of interesting points regarding identification and triggers of OTC deficiency."

Clinical • Ataxia • Cardiovascular • CNS Disorders • Epilepsy • Hypotension • Immunology • Metabolic Disorders • Movement Disorders • Psychiatry • Schizophrenia

Influence of implementing a protocol for an intravenously administered ammonia scavenger on the management of acute hyperammonemia in a pediatric intensive care unit. (PubMed, J Inherit Metab Dis) - "This study is the first to compare two SBSP delivery strategies in the treatment of acute hyperammonemia in this PICU setting. Implementation of a delivery protocol shortened the time from diagnosis of hyperammonemia to prescription of SBSP and helped us identify other parameters that can be improved to optimize treatment delivery."

Clinical • Journal