A 24-year-old female is brought to the emergency department (ED) after an episode of witnessed seizure activity in her home. Her mother says that she has a history of generalized tonic-clonic seizures. She has been seizure-free for the past six years. She stopped taking all her medications two years ago. Her only current daily medication includes a multivitamin and an oral contraceptive pill. At the ED, she is given a loading dose of IV fosphenytoin and started on maintenance doses of oral phenytoin. Over the next three days, she does not have any further seizures. On the fourth day, she has developed a horizontal nystagmus. Her total phenytoin level on the same day is 20 mcg/mL (normal range is10-20 mcg/mL). Repeat blood work returns with the same value. Which of the following is the most appropriate next step?

Question

A 24-year-old female is brought to the emergency department (ED) after an episode of witnessed seizure activity in her home.  Her mother says that she has a history of generalized tonic-clonic seizures.  She has been seizure-free for the past six years.  She stopped taking all her medications two years ago.  Her only current daily medication includes a multivitamin and an oral contraceptive pill.  At the ED, she is given a loading dose of IV fosphenytoin and started on maintenance doses of oral phenytoin.  Over the next three days, she does not have any further seizures.  On the fourth day, she has developed a horizontal nystagmus.  Her total phenytoin level on the same day is 20 mcg/mL (normal range is10-20 mcg/mL).  Repeat blood work returns with the same value.  Which of the following is the most appropriate next step?

Quizplus · Accepted Answer

Explanation: It is important to recognize the early signs and symptoms of phenytoin toxicity. The earliest sign is the presence of nystagmus on far lateral gaze. Some other effects include blurred vision, diplopia, ataxia, slurred speech, dizziness, drowsiness, lethargy, and decreased mentation, which progresses to coma. Systemic side effects and neurotoxicity is one of the major limitations to the use of phenytoin. Usual therapeutic range of phenytoin is between 10-20 mcg/mL and most patients will experience adverse dose related neurotoxic effects with levels greater than 20 mcg/mL. However, the serum levels associated with neurotoxicity vary from patient to patient. Some patients can experience side effects even when the measured levels are within the normal therapeutic range. The first step in the management of side effects due to higher drug levels is to reduce the dose or alter the treatment schedule to minimize the peak drug levels. Therefore, in this vignette, the dose of phenytoin should be reduced and patient should be observed for resolution of nystagmus. (Choices A and B) Abrupt cessation of an antiepileptic drug is not recommended. Any antiepileptic drug that needs to be withdrawn due to intolerable side effects should be tapered gradually (over days to weeks) to prevent seizure relapse. (Choice C) The dosage of the drug should be reduced to prevent further toxicity. Observation alone is not appropriate. (Choice D) Oral contraceptive pills do not affect the drug level of phenytoin. Conversely, chronic phenytoin therapy can cause failure in contraception by enhancing the metabolism of oral contraceptive pills through the induction of hepatic enzymes. Educational objective: Patients with signs and symptoms of phenytoin toxicity should be initially managed by altering the drug dosage or treatment schedule to minimize drug peak levels. References: Clinical features and management of poisoning due to phenytoin. (http://www.ncbi.nlm.nih.gov/pubmed/2671594)

A 24-Year-Old Female Is Brought to the Emergency Department (ED) After an Episode