title: Valproate-induced reversible sensorineural hearing loss: a case report with serial audiometry and pharmacokinetic modelling during a valproate rechallenge.
abstract: Hearing loss has been reported with valproic acid (VPA) use. However, this is the first case of VPA-induced hearing loss that was tested and confirmed with a VPA rechallenge, supported by serial audiometry and pharmacokinetic modelling. A 39-year-old truck driver with temporal lobe epilepsy was treated with VPA at 400 mg, twice daily, and developed hearing loss after each dose, but recovered within three hours. Hearing loss fully resolved after VPA discontinuation. Audiometry performed five hours after VPA rechallenge showed significant improvement in hearing thresholds. Pharmacokinetic modelling during the VPA rechallenge showed that hearing loss occurred at a level below the therapeutic range. Brainstem auditory evoked potential at three months after VPA discontinuation showed bilateral conduction defect between the cochlear and superior olivary nucleus, supporting a pre-existing auditory deficit. VPA may cause temporary hearing threshold shift. Pre-existing auditory defect may be a risk factor for VPA-induced hearing loss. Caution should be taken while prescribing VPA to patients with pre-existing auditory deficit.
authors.affiliation: Department of Pharmacy, University of Malaya, Kuala Lumpur.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Yeap
authors.affiliation: Division of Neurology, Department of Medicine, University of Malaya, Kuala Lumpur.
authors.forename: Kheng-Seang
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Department of Pharmacy, University of Malaya, Kuala Lumpur.
authors.forename: Yoke-Lin
authors.initials: YL
authors.lastname: Lo
authors.affiliation: Department of Otorhinolaringology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mohd Zukiflee Abu
authors.initials: MZ
authors.lastname: Bakar
authors.affiliation: Division of Neurology, Department of Medicine, University of Malaya, Kuala Lumpur.
authors.forename: Chong-Tin
authors.initials: CT
authors.lastname: Tan
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001299:Audiometry; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D008297:Male; D014635:Valproic Acid / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid
keywords: AED; epilepsy; hearing loss; ototoxicity; pharmacokinetics; side effects; valproic acid