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.
A prospective study was undertaken in 16 patients with chronic renal failure on continuous ambulatory peritoneal dialysis, with 22 episodes of peritonitis treated with vancomycin, a known ototoxic agent. Twelve patients had one episode each, and four had recurrent peritonitis. Each treatment course consisted of two infusions of vancomycin (30 mg/kg body weight) in 2 L of peritoneal dialysate administered at 6-day intervals. Serum vancomycin analyzed by enzyme immunoassay showed a mean trough level of 11.00 microg/ml on day 6 and mean serum levels of 33.8 and 38.6 microg/ml about 12 hours after administration on days 1 and 7, respectively. Similar levels, well within the therapeutic range, were encountered with repeated vancomycin therapy for recurrent episodes of peritonitis, suggesting that no changes occurred in the pharmacokinetic profile of the drug. Pure-tone audiometry, electronystagmography, and clinical assessment performed during each course of treatment showed no evidence of ototoxicity even on repeated courses of vancomycin therapy. The results suggest that vancomycin therapy when given in appropriate concentrations as a single therapeutic agent is both effective and safe. We believe, however, that vancomycin administered in combination with an aminoglycoside may produce ototoxic effects that may be greatly aggravated, possibly because of synergism.