#3018 Aciclovir or valaciclovir neurotoxicity in renal patients: increasing number of neurotoxicity cases are diagnosed in Sweden by a blood test

Abstract Background and Aims Kidney transplant patients are at high risk for developing zoster infections, as well as patients with impaired renal function. Aciclovir (ACV) and its prodrug valaciclovir are effective medications to treat these herpes infections. The medications typically have mild side effects such as nausea and vomiting, headache, and skin rash. More uncommon but serious side effects include elevated creatinine, acute kidney failure, and aciclovir-induced neuropsychiatric symptoms (AINS). The latter is difficult to distinguish from the viral infection treated, thus prolonged treatment with ACV may cause further deterioration and increase the chance for coma and need for intensive care treatment. ACV is excreted by glomerular filtration and tubular secretion and should be doses according to renal function. A small part is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase to its main metabolite 9-carboxymethoxymethylguanine (CMMG), but as renal function decreases more CMMG is found in the urine, serum, and CSF. We have earlier shown that a serum CMMG cut-off level of 10.8 µmol/L is predictive of AINS. Hemodialysis alleviates the symptoms dramatically, but AINS need to be diagnosed first. The knowledge about our method has increased in Sweden, but has more AINS cases been diagnosed in Sweden now than for 10 years ago? Method Data from our therapeutic drug monitoring (TDM) database of ACV and CMMG levels were studied during the period 2013 to 2023. Serum samples with a CMMG concentration above 10.8 µmol/L were collated and compared to the total number of samples per year. Some patients were monitored with more than one blood sample during the treatment period and the number of single patients was also included. Results The database consisted of 4521 serum ACV and CMMG samples during the study period with 727 samples with a CMMG concentration above 10.8 µmol/L. The number of CMMG serum samples increased from 278 in 2013 to 601 in 2023. A total of 363 patients had at least one sample above 10.8 µmol/L. A median of 33 (range 17 to 59) single patients were diagnosed with AINS per year. Conclusion Measurement of both ACV and CMMG has increased the number of AINS cases in Sweden and are requested to a higher extent now than 10 years ago. Two more laboratories in Sweden measure or will start to measure ACV and CMMG, one laboratory in Bristol have had the method since 2007, but there are too few laboratories performing the analysis in other countries, causing severe suffering for patients and high costs for healthcare.