Measurement of levetiracetam drug levels to assist with seizure control and monitoring of drug interactions with other anti-epileptic medications (AEMs)

Stepanova, Daria; Beran, Roy G.

doi:10.1016/j.seizure.2014.02.003

Cited by 43 publications

(55 citation statements)

References 22 publications

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“…[8][9][10][11]14,15 In the current study, ngLEV was also well tolerated. Less than 10% of the total analyzed patients had mild LEVrelated side-effects (slight rash and somnolence).…”

Section: Discussionmentioning

confidence: 50%

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Early enteral levetiracetam in diazepam‐resistant convulsive status epilepticus

Shibata

Yonemitsu

Ueda

et al. 2016

Neurology & Clinical Neurosc

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Background: Levetiracetam is used intravenously as an emergent initial and urgent control therapy for acute convulsive status epilepticus. However, the efficacy of early enteral levetiracetam has not been confirmed in cases of benzodiazepine-resistant convulsive status epilepticus. Aim: We evaluated the efficacy and safety of levetiracetam administration through a nasogastric tube in acute convulsive status epilepticus resistant to intravenous diazepam. Methods: In a single-center prospective study, we assigned convulsive status epilepticus patients previously treated with intravenous diazepam (20 mg maximum) to either the terminated seizure group or continued seizures group. In both groups, the patient received 1500 or 3000 mg of levetiracetam enterally within 30 min after diazepam according to primary seizure cessation, and the daily enteral levetiracetam maintenance dose after admission was set to the same amount as the initial levetiracetam dose. The primary end-point was the efficacy of enteral levetiracetam within 30 min after diazepam in the diazepam-resistant group. Results: In eight of nine diazepam-resistant patients (88.9%) and 11 of 12 (91.7%) diazepam-responders, the seizures were controlled within 30 min after diazepam (P = 1.00), and the 3-day seizure freedom rate was equivalent in the two groups (88.9 vs 83.3%, P = 1.00). Less than 10% of the overall patients had levetiracetam-related mild side-effects (no differences between the two groups). Conclusions: Throughout the 3-day acute stage, early enteral levetiracetam just after intravenous diazepam is effective for both primary control of ongoing seizures and preventing seizure recurrence, even in diazepam-resistant convulsive status epilepticus, without serious side-effects.

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“…[8][9][10][11]14,15 In the current study, ngLEV was also well tolerated. Less than 10% of the total analyzed patients had mild LEVrelated side-effects (slight rash and somnolence).…”

Section: Discussionmentioning

confidence: 50%

“…15 The DZP-resistant group had a higher blood LEV level than the DZP-responders. One plausible reason for the significant difference between two groups was that the DZP-resistant group included a greater number of ngLEV 3000 mg patients ( Table 2).…”

Section: Discussionmentioning

confidence: 91%

Early enteral levetiracetam in diazepam‐resistant convulsive status epilepticus

Shibata

Yonemitsu

Ueda

et al. 2016

Neurology & Clinical Neurosc

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“…It was shown that patients may reach optimal seizure control with AED plasma levels often below reference ranges. [44][45][46] Individual reference ranges (referring to drug levels associated with a response in an individual patient) might also be more useful in clinical practice, 10,39,[47][48][49] but assessing this aspect went beyond our aims.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment

Aícua‐Rapún

André

Rossetti

et al. 2019

Annals of Neurology

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Objective Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is widely established for older generation AEDs, whereas there is limited evidence about newer AEDs. Our aim is to assess the benefit of TDM of newer generation AEDs in epilepsy. Methods We performed a randomized, controlled trial comparing systematic with rescue TDM of lamotrigine, levetiracetam, oxcarbazepine, topiramate, brivaracetam, zonisamide, or pregabalin. Participants were adults with epilepsy, in whom treatment with newer generation AEDs was initiated or needed adjustment. In the systematic TDM arm, AED plasma levels were available at each appointment, whereas in the rescue TDM arm, levels were known only if a study endpoint was reached (inefficacy or adverse events). The primary outcome was the proportion of participants followed 1 year without reaching one of the predefined endpoints. Results A total of 151 participants were enrolled; global retention in the study was similar in both arms (56% overall, 58% in the systematic, and 53% in the rescue TDM arm, p = 0.6, Cox regression). There was no difference in terms of outcome regarding treatment efficacy or tolerability. Partial adherence of clinicians to TDM (adjusting or not AED dosage based on blood levels) did not explain this lack of benefit. Interpretation This study provides class A evidence that systematic drug level monitoring of newer generation AEDs does not bring tangible benefits in the management of patients with epilepsy. Poor correlation between clinical effects and drug levels likely accounts for this finding. However, TDM is useful in several situations, such as pregnancy, as well as when there are compliance issues. ANN NEUROL 2020;87:22–29

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“…A recent report suggests that high doses may still be possible without toxicity. 1 Purpose To describe the importance of therapeutic drug monitoring (TDM) of LEV for minimising toxicity when it is used at doses higher than recommended. Material and methods Casereportof57-years-oldmalediagnosedwith symptomaticfocalepilepsyandhumanimmunodeficiencyvirus(HIV).…”

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confidence: 99%

4CPS-175 Safe use of levetiracetam at doses higher than the maximum recommended

Fernández

Roig

Sanchez

et al. 2018

Section 4: Clinical Pharmacy Services

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BackgroundLevetiracetam (LEV) is a second-generation antiepileptic drug used as a unique or adjunctive therapy for treating partial or generalised epilepsy. Its maximum dose according to the summary product is 3000 mg/day. In patients with resistant epilepsy sometimes it is used at doses higher than recommended. A recent report suggests that high doses may still be possible without toxicity.1 PurposeTo describe the importance of therapeutic drug monitoring (TDM) of LEV for minimising toxicity when it is used at doses higher than recommended.Material and methodsCase report of 57-years-old male diagnosed with symptomatic focal epilepsy and human immunodeficiency virus (HIV). Antiepileptic treatment consists of LEV 4000 mg/day, topiramate 300 mg/day and clonazepam 4 mg/day since 2010 plus lacosamide 200 mg/day added in 2015. In September 2016 he had a new neurological crisis and dosage was increased to 4500 mg/day. Antiretroviral medication (AM) was changed in 2013 from tenofovir/efavirenz/emtricitabine to abacavir/lamivudine plus efavirenz. In January 2017 AM medication was simplified to dolutegravir/abacavir/lamivudine.ResultsLEV trough plasma levels (LEVTPL) were 35.9 µg/mL (therapeutic range is 10–40 µg/mL) at the beginning of 2016, 6 years after treatment with LVT 4000 mg/day, glomerular filtration (GFR) calculated by CKD-EPI was >60 ml/min/1.73 m2 and the patient did not have clinical signs of toxicity. Three months after increasing LEV dose to 4500 mg/day the patient presented symptoms of intoxication, felt tired and sleepy. TDM confirmed supratherapeutic LEVTPL of 67.1 µg/mL accompanied by a slight deterioration of renal function (GFR: 50 ml/min/1.73 m2). Concomitant medication seemed not to interact with LEV. LEV dose was reduced to 3500 mg/day. Three months’ later, LEVTPL values returned to normal (36.3 µg/mL) and clinical signs of toxicity disappeared.ConclusionLEV at doses higher than recommended could be used safely if there is a close TDM programme to ensure treatment effectiveness and minimise adverse effects.References and/or Acknowledgements1. Stepanova D, Beran R. Measurement of levetiracetam drug levels to assit with seizure control and monitoring of drug interactions with other Anti-Epileptic Medication (AEMs). Seizure2014;23:371–376.No conflict of interest

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Measurement of levetiracetam drug levels to assist with seizure control and monitoring of drug interactions with other anti-epileptic medications (AEMs)

Abstract: LEV range (20-40mg/L) assisted epilepsy management and anti-epileptic medication interactions were suggested with polytherapy thus possibly explaining the impaired efficacy of LEV with polytherapy.

Cited by 43 publications

References 22 publications

Early enteral levetiracetam in diazepam‐resistant convulsive status epilepticus

Early enteral levetiracetam in diazepam‐resistant convulsive status epilepticus

Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment

4CPS-175 Safe use of levetiracetam at doses higher than the maximum recommended

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