The Case Files

Abstract

Figure: Corrected Phenytoin Concentration v. Dose of PhenytoinFigureFigureFigureFigureA 63-year-old man presented with hand tremors, dizziness, and expressive aphasia. His symptoms had started a month earlier, and this was his third visit to the ED for these symptoms, though the aphasia was a new symptom. He said his symptoms had been growing worse. The patient's symptoms had been previously attributed to alcohol intoxication. He also said he had been experiencing vomiting, dry heaving, bilateral tinnitus, and dizziness but no fever, chills, chest pain, abdominal pain, shortness of breath, vision and hearing problems, gait problems, vertigo, numbness, or loss of consciousness. He had had multiple falls due to dizziness but no head or neck trauma. He occasionally had constipation but no other symptoms. His history included right leg deep vein thrombosis, left shoulder replacement, epilepsy, anxiety disorder, panic attacks, and benzodiazepine and opiate dependence. He had been in a methadone program for 25 years for heroin abuse, but he had stopped all benzodiazepines a month before his ED visit because his primary care physician advised him not to mix them with alcohol. His medications were alprazolam, cholecalciferol, phenytoin, folic acid, meclizine, and naproxen. He reported daily alcohol and cannabis use. His temperature was 98.3°F, pulse was 75 bpm, respiration rate was 20 bpm, blood pressure was 167/108 mm Hg, and oxygen saturation was 98% on room air. The patient was alert and oriented times four but anxious and confused. His pupils were round, equal, and reactive to light with bilateral horizontal nystagmus. The patient was able to follow commands but unable to converse due to confusion. He had an ataxic gait but an otherwise unremarkable examination. His laboratory findings were a WBC of 6.7k/μL, RBC of 4.38 M/μL, Hbg of 14.5 g/dL, hematocrit of 43.4%, MCV of 99 FL, ALT of 53 IU/L, AST of 60 IU/L, albumin of 3.8 g/dL, and serum phenytoin of 36.6 mcg/mL. The patient's phenytoin was stopped, and he was admitted to monitor his drug level and breakthrough seizures. He regained cognitive and motor stability once his drug level dropped below therapeutic levels. He was discharged five days later with levetiracetam 500 mg BID.TableSerum Monitoring Phenytoin can be used nonemergently to treat complex partial and tonic-colonic seizures and emergently to treat status epilepticus. It has a narrow therapeutic serum range of 10-20 mcg/mL. (N Engl J Med 1985 18;313[3]:145; Br J Clin Pharmacol 1974;1[2]:163; http://bit.ly/2qCKcqA.) Phenytoin toxicity was more common in the past, but incidence is much lower now because other antiepileptic medications have better side-effect profiles and dose management. Many studies have reported that adverse symptoms of phenytoin depend on the serum concentration levels. (Table.) (Proc Singapore Health 2013;22[3]:198; http://bit.ly/2PgjX8a; DRUGDEX System: Truven Health Analytics; 2013; www.micromedexsolutions.com; Lexicomp. Phenytoin. https://online.lexi.com.) Phenytoin serum values are corrected based on albumin levels using the Sheiner-Tozer formula. This corrected serum concentration standardizes the value to allow for comparison between individuals. (Ann Pharmacother 1995;29[7-8]:667.) This patient's serum albumin of 3.8 g/dL and phenytoin of 36.6 mcg/mL resulted in a corrected phenytoin value of 42.56 mcg/mL, supporting the patient's symptoms of confusion, horizontal nystagmus, ataxia, slurred speech, nausea, and vomiting. The most common treatment is to replace the medication with another anticonvulsant (mostly levetiracetam), which is better tolerated and has fewer adverse effects. (Neurocritical Care 2014;21[2]:228.) Patients on long-term phenytoin require constant serum monitoring and dose corrections. (N Engl J Med 1985 18;313[3]:145.; Br J Clin Pharmacol 1974;1[2]:163; http://bit.ly/2qCKcqA.) Monitoring is necessary because of the exponential relationship between corrected phenytoin concentration v. the phenytoin dose. (Figure.) It displays that the therapeutic dose range is within ~50 mg/kg. This narrow window makes it easy to be in nontherapeutic range when under treatment. With a slight increase, it reaches toxic levels, with the patient presenting with the correlated symptoms shown in the table. Constant serum monitoring is troublesome, but follow-up is more difficult for those with a history of illicit drug and alcohol abuse, like our patient. The dose is not the only factor that can lead to elevated serum levels in the blood; a slight decrease in liver function through cirrhosis, malnutrition, or aging can also cause the drug serum concertation to rise. (Epilepsy Res 2006;68[Suppl 1]:S49; http://bit.ly/2JSp0G3.)