meropenem and Drug-Overdose

Valproic acid (VPA) and derivatives are effective anticonvulsants that are also used for numerous mood disorders. VPA toxicity can cause central nervous system (CNS) depression, dose related hyperammonemia, and eventually hepatotoxicity. While traditional treatment of VPA toxicity often includes l-carnitine, activated charcoal, and hemodialysis; an interaction with carbapenem class antibiotics has been well established in literature and may offer a different avenue of treatment. This case describes a 38 year-old female with a past medical history of epilepsy effectively treated with meropenem to rapidly and safely lower toxic VPA levels after an acute ingestion. A review of four VPA poisoning case reports and the interaction with carbapenem class antibiotics is also included.

Topics: Adult; Anti-Bacterial Agents; Anticonvulsants; Carbapenems; Drug Overdose; Epilepsy; Female; Humans; Meropenem; Valproic Acid

Valproic acid (VPA) is a broad-spectrum antiepileptic drug indicated for monotherapy and adjunctive therapy of seizures, and complex manic episodes associated with bipolar disorder [1]. While uncommon due to monitoring, VPA can cause toxicity at supratherapeutic levels [1, 2]. Traditional treatment for VPA toxicity is primarily supportive care, however activated charcoal, l-carnitine, and hemodialysis have been successful in removing free VPA [2]. An interaction between carbapenem antibiotics and VPA is well-established and listed in respective package inserts as a combination to be avoided due to decreased VPA efficacy [1, 3]. Recent literature suggests co-administration of meropenem with VPA reduces mean plasma VPA levels by 50-80% [4, 6]. This case report describes the successful use of carbapenems to intentionally lower toxic VPA levels in a 42 year old female that presented to the emergency department with VPA toxicity from an overdose with divalproex sodium.

Topics: Adult; Anti-Bacterial Agents; Anticonvulsants; Antidotes; Drug Overdose; Female; Humans; Meropenem; Valproic Acid

Objectives Valproic acid (VPA) is an anticonvulsant used in several clinical scenarios. VPA has been increasingly associated with intentional or unintentional overdose. In patients presenting with severe VPA overdose, supportive care and airway protection are cornerstones of treatment, while levocarnitine is suggested in patients with hyperammonemia and hemodialysis is recommended in patients with VPA serum concentrations (SC) >1,300 mg/L and presence of cerebral edema or shock. Meropenem is a carbapenem antibiotic with a broad spectrum of activity. The pharmacological interaction between VPA and meropenem is characterized by a rapid decrease in VPA concentrations, which contraindicates concurrent use. Case presentation The following case report describes the use of meropenem to enhance the clearance of VPA in the case of severe VPA overdose. A patient with altered mental status was transported to the emergency department (ED) after VPA overdose. Meropenem was prescribed for significant elevated VPA SC. An important decline in SC was observed with short-term meropenem dosing, and an improvement in mental status occurred shortly after administration. Conclusions Carbapenem therapy has the potential to be used as last line strategy in the management of severe VPA overdose in patients where SC represent a significant risk of toxicity and clinical symptoms suggest difficulty managing the patient.

Topics: Administration, Oral; Adult; Anticonvulsants; Drug Overdose; Emergency Service, Hospital; Female; Humans; Mental Disorders; Meropenem; Valproic Acid

Overdose of valproic acid (VPA) or its derivatives can cause significant toxicities such as hyperammonemia or altered mental status. While levocarnitine has been used historically to manage VPA-associated hyperammonemia, no standard of therapy exists to manage VPA toxicity. We present a case of VPA overdose managed with meropenem in addition to levocarnitine. A 38-year old female presented to the emergency department after intentionally ingesting 20 tablets of extended release divalproex sodium. She received a 4-gram loading dose of levocarnitine. She developed altered mental status, and a repeat VPA level yielded a result of 278 μg/mL. She was given 1 g of meropenem and her subsequent VPA level was 193 μg/mL. Approximately 8 h after the initial dose, another 1 g of meropenem was administered. Additionally, she received 1 g of levocarnitine every 4 h for a total of six doses. A repeat VPA level returned at 62 μg/mL. The patient was transferred to the intensive care unit for further management. Carbapenem antibiotics inhibit acylpeptide hydrolase in the gastrointestinal tract. Inhibition of this enzyme prevents the reabsorption of metabolized VPA and therefore causes increased elimination. Our patient demonstrated a rapid lowering of VPA levels after administration of meropenem.

Topics: Adult; Anti-Bacterial Agents; Antimanic Agents; Drug Overdose; Female; Humans; Meropenem; Valproic Acid