P: 65 Drug-induced Hyperammonaemia: Data From VigiBase, the WHO Database

Abstract

BACKGROUND: Altered consciousness secondary to metabolic encephalopathies represents a major cause of ICU admission with favorable outcome when diagnosed and treated rapidly. Ammonia dosage is thus recommended in most textbooks in the absence of any diagnosis after etiological work-up encompassing biological sampling, cerebral imaging and EEG. Despite hyperammonaemia is most commonly secondary to liver diseases, portosystemic shunts, inborn errors of metabolism, mostly urea cycle defects, microbial pullulation or drug-induced hyperammonaemia (DIH) are other possible causes. DIH is poorly described but is mainly recognized as the consequence of valproic acid. Some antineoplastic agents, fluorouracile or asparaginase, have been implicated but this class is evolving rapidly. To describe the drugs associated with DIH. METHODS: We used VigiBase, the WHO global Individual Case Safety Report (ICSR) database, which contains reports of suspected adverse drug reactions (ADRs) collected by national drug authorities in over 130 countries between 1967 and 8 May 2019. This observational retrospective study included all ADRs reported as "hyperammonaemia" according to the Medical Dictionary for Drug Regulatory Activities (MedDRAv21.1) term (Prefered term [PT] level). The drugs considered in the analysis were those notified as suspected treatments. Drugs used to treat hyperammonaemia or hepatic encephalopathy were excluded as were drugs reported less than 3 times. Drugs with a positive lower end of the 95% credibility interval for the information component (IC025) ≥0, an indicator value for disproportionate Bayesian reporting, was considered as causative of hyperammonaemia. RESULTS: Among 19 438 165 ICSRs, 576 drugs were identified for the term "hyperammonaemia [PT]". Six were excluded because they were used to treat hyperammonaemia or hepatic encephalopathy. Thus, 73 drugs had a an IC025 ≥0 and represented 2759 cases (0.014%). Twelve drugs were reported more than thirty times (Table 1). CONCLUSION: Besides commonly involved drugs, some other commonly used drugs seem associated in DIH. These data could help in the etiological work-up of hyperammonemia.