CX, a 43-year-old male, presented to the ED after being found unconscious in his office at home by his wife.

PMH: Diabetes, Hyperlipidemia, Epilepsy (Generalized Tonic-Clonic)

Weight 80 kg, Height 71 in

Vitals: BP 145/82 mmHg, HR 97 bpm

Labs upon arrival:

A1c 5.9%

TC 147 mg/dL, LDL 65 mg/dL, HDL 38 mg/dL, TG 102 mg/dL

SCr 0.7 mg/dL, Albumin 3.0 g/dL

Current medications:

Metformin 1000 mg BID

Atorvastatin 20 mg QD

Levetiracetam 1000 mg BID

Upon arrival to the hospital, CX began having continuous tonic-clonic seizures for about 8 minutes, which was consistent with status epilepticus (SE). He was quickly intubated, and a dose of Ativan 4 mg IV was administered as initial emergent treatment. Despite receiving a 2^nd dose of Ativan, CX continued to seize over the next few minutes. The ED physician determined that urgent therapy is needed and decided to give the patient Dilantin 1600 mg (20 mg/kg) as a loading dose infused over 30 minutes. CX remains in SE even after the infusion was finished, which prompted the physician to obtain a phenytoin level to determine the next steps.

Total phenytoin level 5.6 mcg/mL

What is CX’s corrected phenytoin level, and is it subtherapeutic or supratherapeutic?

A. 6 mcg/mL; subtherapeutic

B. 6 mcg/mL; supratherapeutic

C. 8 mcg/mL; subtherapeutic

D. 8 mcg/mL; supratherapeutic

Answer with Rationale

Status epilepticus (SE) is a medical emergency characterized by at least 5 minutes of continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery between seizures. Delays in care can lead to significant morbidity or mortality. Acute processes (cerebrovascular event, cardiac arrest, metabolic disturbances, drug toxicity/withdrawal, CNS infection, head trauma, etc.) and chronic processes (anticonvulsant withdrawal, chronic alcohol use, CNS tumors, etc.) can both cause an individual to go into SE. Complications of SE include increased systemic BP, hyper- or hypoglycemia, hyperkalemia that can lead to arrhythmias, lactic acidosis, neurologic damage, etc. Status epilepticus requires prompt and organized treatment, with simultaneous supportive care (airway, breathing, circulation) and administration of antiepileptic drug (AED) therapy.

For patients with CrCl > 10 mL/min, the process for calculating corrected phenytoin in our patient is as follows:

The therapeutic range of phenytoin to target in patients treated for SE is 10-20 mcg/mL for total phenytoin levels and 1-2 mcg/mL for free phenytoin levels. 

Answers A & B are incorrect. Albumin is a protein that serves as a major source of drug binding. Since phenytoin is highly protein-bound (90%), correction for hypoalbuminemia is needed when albumin is ≤ 3.2 g/dL. Since CX’s albumin was 3.0 g/dL, a corrected phenytoin level must be calculated for CX to accurately access his treatment.

Answer C is correct. CX’s true total phenytoin level, after correction for hypoalbuminemia, is 8 mcg/mL, as calculated above. This value is below the therapeutic range of 10-20 mcg/mL. 

Answer D is incorrect. CX’s true total phenytoin level, after correction for hypoalbuminemia, is 8 mcg/mL, as calculated above. This value is NOT above the therapeutic range of 10-20 mcg/mL.

Generic/Brand: Metformin (Glucophage), Atorvastatin (Lipitor), Levetiracetam (Keppra), Lorazepam (Ativan), Phenytoin (Dilantin)

NAPLEX Core Competencies Covered:

• 1.5 – Signs or symptoms of medical conditions, healthy physiology, etiology of diseases, or pathophysiology
• 2.2 – Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied
• 4.1 – Patient parameters or laboratory measures
• 4.5 – Drug concentrations, ratio strengths, osmolarity, osmolality, or extent of ionization