meropenem and Epilepsy

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

The purpose of this article is to review the safety and tolerance of two carbapenems (imipenem/cilastatin and meropenem) in order to establish their possible use in different clinical settings. The tolerance and safety profile of both carbapemens in intravenous and intramuscular formulation is good. With imipenem/cilastatin, nausea and vomiting can constitute a practical problem requiring prolonged times of perfusion and high dilutions. The possibility of administering meropenem in intravenous infusion or bolus injection with lower volumes of fluid, without increasing the incidence of these adverse reactions, may have practical advantages in special situations. The possible neurotoxicity of the imipenem/cilastatin presents limitations of the use in high risk circumstances such as meningitis, previous alterations of CNS, renal insufficiency and concomitant administration of other drugs with neurotoxic profiles and when high doses of administration are needed. The meropenem, by the contrary, can be used in patients with infections of the CNS and other risk factors, at high doses, without increased risk of seizures.

Topics: Animals; Cilastatin; Drug Interactions; Epilepsy; Humans; Imipenem; Injections, Intramuscular; Kidney; Meropenem; Nausea; Opportunistic Infections; Thienamycins; Vomiting

The literature has described the interaction between valproic acid  and carbapenems. This interaction leads to decreases in plasma concentrations  of valproic acid. The main objectives of this study were  to assess its relevance in clinical practice, to identify variables associated with  increased seizure episode rates, and to analyse the impact of pharmaceutical intervention on avoiding the effects of this interaction.. An observational retrospective study of inpatients with epilepsy  admitted between 2016 and 2020. Their pharmacological treatment throughout  admission was recorded, and the presence of other interactions  leading to decreased plasma concentrations of valproic acid was reviewed. The  seizure rate during the year prior to admission was compared to that during  the interaction period. For every episode in which the interaction was detected, an intervention was conducted by providing the prescriber with information on  the interaction and suggesting a change of antibiotherapy as well as the  pharmacokinetic monitoring of valproic acid.. 37 episodes were included. 58.1% of the patients were male and  median age was 70 years. In total, 56.8% of the patients received meropenem  and 43.2% received ertapenem. The median duration of  concomitant treatment with valproic acid and carbapenem was 4 days. The  incidence rate ratio was 2.60 (95% confidence interval: 1.61-4.21). Thus, this  interaction was associated with a higher seizure rate. A statistically significant  association was found between higher seizure rates and patients treated with  more than one anti-epileptic drug. Hospital pharmacists detected 24 episodes  (64.9%). In total, 17 interventions (70.8%) were accepted and 13  combinations were discontinued. Pharmacokinetic monitoring was conducted in  13 episodes (35.1%) and infratherapeutic levels were found in all of them.. The interaction between valproic acid and meropenem or ertapenem is clinically relevant. It is recommended that this combination should be avoided provided that a viable alternative is available.  Pharmaceutical intervention may contribute to preventing seizures associated with this combination.. Objetivo: La interacción entre ácido valproico y carbapenems está descrita en  la literatura y conlleva una disminución de los niveles plasmáticos de ácido  valproico. Los objetivos son evaluar su relevancia en la práctica clínica, conocer  las variables que se asocian a un incremento de crisis epilépticas y  analizar el impacto de la intervención farmacéutica para evitar las  consecuencias de dicha interacción.Método: En este estudio observacional retrospectivo se estudiaron pacientes  con epilepsia hospitalizados entre 2016 y 2020. Se registró el tratamiento  farmacológico prescrito en el ingreso y se revisó la presencia de otras  interacciones que redujeran la concentración plasmática de ácido valproico. La  frecuencia de crisis epilépticas durante el año previo al ingreso se comparó con  la correspondiente al periodo de interacción. Se realizó una intervención  en todos los episodios con la interacción detectada informando al prescriptor  sobre la interacción y proponiendo sustitución de la antibioterapia, así como  monitorización farmacocinética de ácido valproico.Resultados: Se incluyeron 37 episodios. El 58,1% eran varones y la mediana  de edad fue de 70 años. El 56,8% de los pacientes recibió meropenem y el  43,2% restante, ertapenem. Para la duración del tratamiento concomitante  entre ácido valproico y el carbapenem prescrito  se obtuvo una mediana de 4  días. Se halló una razón de tasas de incidencia de 2,60 (intervalo de confianza  del 95%: 1,61-4,21), por lo que esta interacción se asocia a una mayor  frecuencia de crisis epilépticas. Se asoció una mayor frecuencia de crisis  estadísticamente significativa en los pacientes tratados con más de un fármaco  antiepiléptico. Los farmacéuticos hospitalarios detectaron 24  episodios (64,9%). Se aceptaron 17 intervenciones farmacéuticas (70,8%) y  se suprimieron 13 combinaciones. Se realizó monitorización farmacocinética en  13 episodios (35,1%) y en todos se hallaron niveles infraterapéuticos. Conclusiones: La interacción entre ácido valproico y meropenem o ertapenem  es clínicamente relevante y se recomienda evitarla siempre que  existan alternativas viables. La intervención farmacéutica puede contribuir a  prevenir las crisis epilépticas favorecidas por esta combinación.

Topics: Aged; Anti-Bacterial Agents; Anticonvulsants; Drug Interactions; Epilepsy; Ertapenem; Humans; Male; Meropenem; Pharmaceutical Preparations; Retrospective Studies; Valproic Acid

Valproic acid (VPA) is commonly used medication to treat seizure disorder and as prophylaxis for bipolar disorder. Acute VPA toxicity can cause varied symptoms ranging from mild drowsiness to severe cerebral oedema and coma. The therapeutic level of VPA is around 50-100 µg/mL and most of it is protein bound. It is mainly metabolised by liver and is eliminated via bile. The metabolites of VPA interfere with urea cycle and cause deficiency in carnitine leading to increase in ammonia levels. The use of carnitine to treat VPA toxicity is well known but it is still unclear if it lowers VPA levels. We report a case of VPA toxicity that did not respond to use of carnitine at 6000 mg orally but was successfully treated using meropenem leading to lowering of VPA levels and also clinical improvement of patient.

Topics: Adult; Anticonvulsants; Carbapenems; Carnitine; Epilepsy; Female; Humans; Meropenem; Valproic Acid

Topics: Adult; Anti-Bacterial Agents; Anticonvulsants; Drug Interactions; Epilepsy; Female; Fructose; Humans; Meropenem; Peritonitis; Postoperative Complications; Thienamycins; Topiramate; Valproic Acid

We describe here a rare case in which valproic acid (VPA) levels were affected by ertapenem but not by meropenem even though ertapenem and meropenem are in the same carbapenem class. A 68-year-old Filipino male treated with valproate for epilepsy and ertapenem for an infectious disease had decreased VPA levels during the first day of ertapenem therapy. His VPA level increased soon after terminating ertapenem therapy. Two types of carbapenems had different drug reactions with concomitant use of VPA in this patient.. Closer monitoring of VPA concentrations are necessitated using carbapenems for treating infection in patients being administered VPA. Another option is the use of anti-epileptic drugs other than VPA if concomitant use with a carbapenem is warranted.

Topics: Aged; Anti-Bacterial Agents; Anticonvulsants; Bacterial Infections; beta-Lactams; Drug Interactions; Drug Monitoring; Epilepsy; Ertapenem; Humans; Male; Meropenem; Thienamycins; Valproic Acid

The pharmacological interaction between meropenem and valproic acid is potentially serious, especially in critically ill patients, resulting in low plasmatic levels of the anticonvulsant. However, to our knowledge, this interaction between meropenem and reduced valproic acid plasma levels has not been reported in the pediatric chilean population. We present two clinical cases of chilean children, thus reporting that this interaction is present in our population, with an aim at educating physicians about the possibility of such interaction.

Topics: Anticonvulsants; beta-Lactamase Inhibitors; Child, Preschool; Drug Interactions; Epilepsy; Fatal Outcome; Female; Humans; Infant; Meropenem; Seizures; Thienamycins; Valproic Acid

Both valproic acid and levetiracetam are anti-epileptic drugs, often used either alone or in combination. The present study compares valproate (VPA) with levetiracetam (LEV) as an intravenous (i.v.) anticonvulsant treatment in intensive care patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) with a high risk of seizures.. A prospective, single-center patient registry of 35 intensive care unit (ICU) patients with onset seizure and/or high risk of seizures underwent an anticonvulsive, first-line single treatment regimen either with VPA or LEV. Plasma concentrations (pc), interactions between drugs in the ICU context, adverse effects and seizure occurrences were observed and recorded.. A significant decrease in the pc in patients treated with LEV was observed after changing from intravenous (160±51μmol/l) to enteral liquid application (113±58μmol/l), corresponding to a 70.3% bioavailability for enteral liquid applications. The pc in VPA patients decreased significantly, from (491±138μmol/l) to (141±50μmol/l), after adding meropenem to the therapy (p<0.05). Three epileptic seizures occurred during anticonvulsive therapy in the LEV group, and two in the VPA group, including one non-convulsive status epilepticus (NCSE).. Though this finding needs further verification, the enteral liquid application of levetiracetam seems to be associated with lower bioavailability than the common oral application of levetiracetam. The use of the antibiotic drug meropenem together with valproic acid leads to lower pc levels in patients treated with of valproic acid. For clinical practice, this indicates the need to monitor the levels of valproic acid in combination with meropenem.

Topics: Administration, Oral; Aged; Aneurysm, Ruptured; Anti-Bacterial Agents; Anticonvulsants; Biological Availability; Brain Ischemia; Critical Care; Drug Interactions; Enteral Nutrition; Epilepsy; Female; Humans; Intensive Care Units; Levetiracetam; Male; Meropenem; Middle Aged; Piracetam; Prospective Studies; Seizures; Subarachnoid Hemorrhage; Thienamycins; Valproic Acid

To test the hypothesis that treatment with cefepime hydrochloride leads to higher incidence of periodic epileptiform discharges compared with treatment with other β-lactams.. Data from hospital pharmacy databases of patients treated with cefepime or meropenem during a 42-month period (from January 1, 2007, through June 30, 2010) were retrospectively crossed with data from the electroencephalography database for the same period.. Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.. Patients who underwent electroencephalographic testing while taking cefepime or meropenem were selected. Only electroencephalographic tests performed during the antibiotic treatment period were considered. Matches were compared with nurses' medication records to ensure that the antibiotic considered was effectively given.. Proportions of patients with continuous epileptiform discharges in the 2 groups were compared using the Fisher exact test.. A total of 1120 patients were treated with cefepime and 1572 patients with meropenem. Electroencephalographic testing was performed during treatment in 59 patients treated with cefepime and 80 treated with meropenem (5.26% vs 5.08%, P = .85). Continuous epileptiform discharges were present in 14 patients in the cefepime group and 3 in the meropenem group (1.25% vs 0.19%, P < .001). Blood creatinine concentration was elevated in 5 of the 17 patients (range, 1.5-4.2 mg/dL; reference range, 0.7-1.2 mg/dL), and liver enzyme levels were elevated in 5 patients. No patient had major electrolyte disturbances.. Our study showed a prevalence of electroencephalographic test results with continuous epileptiform discharges in 14 of 1120 patients receiving cefepime (1.25%) but only 3 of 1572 patients receiving meropenem (0.19%). Contrary to the results of previous case series, these electroencephalographic patterns occurred, in most cases, in patients with normal renal function. These results suggest that cefepime may be an independent risk factor for periodic epileptiform discharges, which are associated with worse outcomes. This finding could provide a partial explanation for the higher mortality rates reported in patients treated with cefepime compared with other β-lactams.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Belgium; Cefepime; Cephalosporins; Cross-Over Studies; Electroencephalography; Epilepsy; Female; Humans; Male; Meropenem; Middle Aged; Pharmacy Service, Hospital; Retrospective Studies; Thienamycins

Topics: Anti-Bacterial Agents; Anticonvulsants; Drug Interactions; Epilepsy; Female; Humans; Infant; Meropenem; Thienamycins; Valproic Acid

Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the treatment of various forms of epilepsy. Concomitant administration of VPA and carbapenem antibiotics such as panipenem/ betamipron and meropenem has been reported to decrease the serum level of VPA. We observed seven cases which showed a decrease in serum levels of VPA due to concomitant use of VPA and carbapenem from January 2002 to October 2006 in a 750-bed university hospital, the average decrease of 70.4% was observed. Carbapenem antibiotics administrated concomitantly with VPA were panipenem (1 case), meropenem (3 cases), and imipenem (2 cases), and in one other case imipenem and meropenem were used sequentially. We found the VPA serum levels were significantly decreased with meropenem (n=4) more than with other carbapenem antibiotics (n=4, 89.3% vs. 51.5% decrease, P=0.03). Clinicians should be aware of this potential interaction, pay attention to the failure of seizure control due to decreased serum VPA levels with concomitant use of carbapenem antibiotics, and monitor VPA serum levels for those cases.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anticonvulsants; Carbapenems; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Thienamycins; Valproic Acid

A 55-year-old woman was diagnosed with pneumonia and was treated with meropenem; 5 days later she developed epileptic seizures. She had been treated with valproic acid for 16 years to control her epileptic seizures. Her serum valproic acid concentration was low during treatment with meropenem than previously recorded despite an increase of valproic dose. As soon as administration of meropenem was withdrawn, valproic acid concentration increased to previous levels and her seizures stopped. Meropenem decreases valproic acid concentration, and may promote the development of epileptic seizures in previously controlled epileptic patients. The acute lowering of serum valproate produced by meropenem probably precludes their concomitant use.

Topics: Anticonvulsants; Drug Interactions; Epilepsy; Female; Humans; Meropenem; Middle Aged; Pneumonia; Thienamycins; Valproic Acid

To report a probable interaction between meropenem and valproic acid that resulted in the development of epileptic seizures.. A 21-year-old woman presented to our emergency department because of a new-onset, generalized tonic-clonic seizure and was admitted to the intensive care unit. Treatment with valproic acid 1000 mg as a continuous intravenous infusion over 24 hours was initiated. On day 6, the serum concentration of valproic acid was 52.5 microg/mL. On day 13, treatment with intravenous meropenem 1 g 3 times daily was started. On day 15, when the patient was afebrile, numerous myoclonic episodes occurred involving her arms and face; the serum concentration of valproic acid at that time was 42 mug/mL. The valproic acid dose was increased to 2880 mg. Two days later, a generalized tonic-clonic seizure occurred despite the increased dosage, and the plasma concentration of valproic acid fell to 7 microg/mL. The valproic acid dose was increased the following day to 3600 mg; however, the serum concentrations remained <10 microg/mL. On day 19, based on the results of a blood culture and the suspicion of an interaction between meropenem and valproic acid, meropenem therapy was suspended. The serum concentration of valproic acid was 52.4 microg/mL on day 27. Three days later, the patient was asymptomatic and was discharged.. Coadministration of valproic acid and other drugs that are metabolized by the hepatic cytochrome P450 isoenzyme system can lead to clinically relevant interactions by induction or inhibition of enzymes in shared metabolic pathways. In view of studies in experimental models, the interaction between carbapenem antibiotics and valproic acid is at least possible. Use of the Naranjo probability scale indicated a probable relationship between acute seizures and a meropenem-valproic acid interaction in this patient.. This case report provides strong evidence for an interaction between valproic acid and meropenem. Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valproic acid serum concentrations.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Anticonvulsants; Drug Interactions; Epilepsy; Female; Humans; Infusions, Intravenous; Meropenem; Seizures; Thienamycins; Valproic Acid

Serum concentrations of valproate were reduced and seizures were exacerbated by concomitant meropenem therapy in a child with a neurodegenerative disorder and epilepsy. In this patient, a rapid decline of valproate serum concentrations was observed on two occasions with meropenem antibiotic therapy. This event was the most likely cause of observed seizure exacerbation. Meropenem should be used with caution in patients treated with valproate owing to the drastic lowering of serum valproate concentration and the consequent risk of seizure worsening.

Topics: Anti-Bacterial Agents; Anticonvulsants; Child; Drug Interactions; Epilepsy; Female; Humans; Meropenem; Neuroaxonal Dystrophies; Thienamycins; Valproic Acid