Multiple drugs
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Elevated alanine transaminase and off label use: case report A 5-year-old boy developed elevated ALT levels while receiving dexamethasone, methotrexate, vincristine and pegaspargase for B-cell acute lymphoid leukaemia and off-label treatment with remdesivir for COVID-19 [not all dosages and routes stated]. The boy was hospitalised in United-Kingdom with a short history of neck swelling, petechiae and fever. He had inspiratory stridor. Initially, he was treated with nebulised epinephrine [adrenaline] and a single dose of oral dexamethasone. Based on the findings of chest X-ray and laboratory parameters including flow cytometry, he was diagnosed with precursor B-cell acute lymphoblastic leukaemia (ALL). He was then transferred to Paediatric ICU (PICU). A nasopharyngeal swab analysis by PCR was found positive for COVID-19. Based on multidisciplinary team discussion, a decision was made to treat him for COVID-19 as he was in early stages of infection and treatment with immunosuppressants for B-cell acute lymphoid leukaemia would further predispose him to severe infection. Thereafter, he received unspecified general anaesthetic for insertion of a Portacath. He also underwent bone marrow aspiration and diagnostic lumbar puncture. Subsequently, he was initiated on off-label (paediatric dosing not yet established) treatment with IV remdesivir 5 mg/kg (loading dose) followed by 2.5 mg/kg on day 2 following admission. Additionally, pegaspargase [pegylated asparaginase], IT methotrexate, IT vincristine and IT dexamethasone were also started the same day. However, on day 3 his ALT began to increase and reached the maximum level of 408 U/L on day 5. By this time, he had received four out of the pre-decided 5 days of treatment. The boy’s remdesivir was withdrawn due to the stipulated compassionate use guidelines. Subsequent COVID-19 testing of nasopharyngeal aspirate by PCR gave negative results for COVID-19. His ALT levels returned to the normal level within 10 days following discontinuation of remdesivir. Thereafter, he was discharged. Subsequent weekly stool tests in the first month remained negative for COVID-19. Follow-up at end of induction chemotherapy showed bone marrow in morphological remission and an undetectable minimal residual disease was noted. Orf K, et al. Remdesivir during induction chemotherapy for newly diagnosed paediatric acute lymphoblastic leukaemia with concomitant SARS-CoV-2 infection. British 803505941 Journal of Haematology 190: e274-e276, No. 5, Sep 2020. Available from: URL: http://doi.org/10.1111/bjh.17014
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Reactions 17 Oct 2020 No. 1826
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