ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Voriconazole and vincristine are major therapeutics in paediatric haematology. However, the risk-benefit ratio of the treatment of invasive aspergillosis with voriconazole in patients receiving vincristine-based chemotherapy remains unclear. CASE DESCRIPTION: We report severe peripheral and central neurological disorders in a 14-year-old girl with T-cell acute lymphoblastic leukaemia and pulmonary aspergillosis. The case describes a strong exacerbation by voriconazole of the vincristine-induced neuropathic pains. It shows the high variability of the trough serum concentration of voriconazole leading to antifungal treatment failure and suggests that its own central neurotoxicity could also be potentiated by vincristine. WHAT IS NEW AND CONCLUSION: Given the risk of either insufficient antifungal efficacy or excessive neurological disorders, this case warns on a probable unfavourable risk-benefit profile of voriconazole during vincristine-based chemotherapy in adolescents.
Subject(s)
Aspergillosis/drug therapy , Nervous System Diseases/chemically induced , Vincristine/adverse effects , Vincristine/therapeutic use , Voriconazole/adverse effects , Voriconazole/therapeutic use , Adolescent , Antifungal Agents/adverse effects , Antifungal Agents/therapeutic use , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/therapeutic use , Female , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapyABSTRACT
PURPOSE: Extrapyramidal disorders associated with veralipride therapy are rarely reported and often due to a drug misuse. METHODS: We evaluated cases of extrapyramidal disorders associated with veralipride. Cases were extracted from the regional pharmacovigilance centre of Amiens database. From January 1, 1995 to September 30, 2004, cases were selected on the basis of the occurrence of extrapyramidal disorders under veralipride therapy. RESULTS: Seventeen cases of veralipride-induced extrapyramidal disorders were found. They consist of 16 menopausal women and one old man with LH-RH antagonist-induced hot flushes. Mean age was 61 years (48-73). Adverse effects were acute dyskinesia (n=2) or parkinsonian syndrome, which occurred after several months or years of treatment (n=15). Parkinsonism was associated with other extrapyramidal symptoms in 8 cases: tardive dyskinesia (n=6), postural tremor (n=3), myoclonia (n=1), and trunk dystonia (n=1). In all cases, outcome was favorable after drug discontinuation. In most cases the tablet-free interval was not respected: this may lead to prolonged striatal D2 receptors blockade. It must be added that the diagnosis was often delayed and patients were considered as suffering from idiopathic Parkinson's disease. CONCLUSIONS: Prescribers should be aware that veralipride is a neuroleptic and could induce potentially severe extrapyramidal disorders. Increase veralipride prescription is expected due to the recent restriction of hormonal replacement therapy for menopause. The physicians should also use veralipride according to the Summary of the Product Characteristics.
