Linezolid and Diphenhydramine Topical: Interaction Details

a) A case report described hyperactive delirium potentially due to anticholinergic drug toxicity in a 56-year-old male following the concomitant administration of diphenhydrAMINE and linezolid. The patient has a history of type 2 diabetes mellitus, contiguous-spread osteomyelitis due to ulcer, and peripheral vascular disease. Prior to admission, the patient was receiving intravenous vancomycin 850 mg every 12 hours plus oral ciprofloxacin 500 mg twice daily for two days along with other medications. The patient presented to the emergency department with a diffuse, erythematous rash and temperature of 39.4 C. Ciprofloxacin was discontinued and vancomycin was increased to 1 g every 12 hours, with 25 mg of diphenhydrAMINE given prior to infusion. Piperacillin/tazobactam 3.375 g every 6 hours and fluconazole 400 mg were given IV daily for antimicrobial protection. Despite these changes, 7 days later the patient presented with persistent rash, skin lesions and purpura on extremities indicating vasculitis. Both antibiotics were discontinued and a new regimen of linezolid 600 mg every 12 hours, metronidazole 500 mg every 8 hours and aztreonam 2 g every 8 hours was initiated. DiphenhydrAMINE 50 mg was given IV every 4 hours to treat pruritus secondary to drug-induced rash. Following 2 days of diphenhydrAMINE, the patient experienced acute onset of symptoms including aggression, paranoia, and visual and auditory hallucinations. The patient became tachycardic (heart rate 110-114 beats/min), had warm skin and was squinting. Symptoms persisted for two to three additional days after diphenhydrAMINE was discontinued. All other laboratory findings were normal. The drug regimen was continued with the exception of diphenhydrAMINE and metronidazole, which was discontinued due to nausea. Four days following the onset of delirium, the patient's behavior returned to normal ¹.