BB is a 48-year-old male who presents to the ED in status epilepticus as a transfer from an outside facility. At the outside facility he was on day 3 of 14 of treatment with Merrem for a P. aeruginosa bloodstream infection. The patient received his last dose of Merrem one hour prior to being transferred. During the transfer, 4 mg of Ativan was administered intravenously twice without cessation of seizure activity. After reviewing the culture and sensitivity report from the outside facility, Merrem was determined to be the best antibiotic option for this patient. The medical resident would like to add on Depacon IV as another antiepileptic agent to control the patient’s seizures. 

Which of the following are true regarding Depacon? (Select all that apply)
A. Depacon would require therapeutic drug monitoring.
B. Depacon serum concentrations could be reduced by Merrem.
C. Depacon exerts its activity via voltage-gated hydrogen channels
D. Depacon has a boxed warning for hepatotoxicity
E. Depacon may require amylase/lipase monitoring if significant abdominal pain, nausea, and vomiting occur. 

Rationale with Explanation:
Status epilepticus is a medical emergency. Continued seizures can cause significant morbidity and mortality if not ceased with drug therapy. The classic drug class used to stop seizure activity are benzodiazepines. In conjunction with these agents, the first-line longer acting drugs used are levetiracetam and phenytoin. These are given IV with the phenytoin typically administered as fosphenytoin so that the administration rate can be 150mg/min as opposed to 50mg/min with phenytoin due to potential hypotension with infusion. IV valproic acid (Depacon) can also be used within the management of status epilepticus.

Answer A is correct. Therapeutic drug monitoring is required typically after a loading dose. If the patient is continued long-term on valproic acid therapy (typically as divalproex), then therapeutic drug monitoring would be continued.

Answer B is correct. If you saw last week's question, one of the rationale explanations would have helped for this week's question. Meropenem belongs to the antibiotic class known as carbapenems. Carbapenems are known to reduce the serum concentration of valproic acid, which can increase the risk of breakthrough seizures. This interaction can occur immediately and be seen for 1-2 weeks following discontinuation of a carbapenem. Therefore, an alternative antiepileptic agent should be used if a carbapenem is the best antibiotic option such as this case where phenytoin or levetiracetam would likely make much more sense. 

Answer C is incorrect. Valproic acid acts through a number of mechanisms of action including affecting sodium and calcium channels but not hydrogen channels. It also likely works through GABA inhibition. 

Answers D and E are correct. Additionally, valproic acid has boxed warnings for both hepatotoxicity and pancreatitis, with both adverse effects being non-dose dependent. Amylase and lipase are enzymes that would be appropriate for evaluating suspected pancreatitis. 

Brands/Generics covered: Merrem (Meropenem); Depacon (Valproic Acid)

NAPLEX Competencies Covered: 
Area 2 (Identify Drug Characteristics), 2.1 Pharmacology, mechanism of action, or therapeutic class; 2.3 Boxed warnings or REMS; Area 3 (Develop or Manage Treatment Plans), 3.2 Therapeutic goals or outcomes and clinical endpoints, 3.6 Drug contraindications, allergies, or precautions, 3.7 Adverse drug effects, toxicology, or overdose 3.8 Drug interactions