Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam (IV LEV), a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of IV LEV and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.
Levetiracetam, trade name Keppra, is a new second generation antiepileptic drug that is being increasingly used in brain tumor patients. In patients suffering with brain tumors, seizures are one of the leading neurologic complications being seen in more than 30% of patients. Unlike other antiepileptic drugs, levetiracetam is proposed to bind to a synaptic vesicle protein inhibiting calcium release. Brain tumor patients are frequently on chemotherapy or other drugs that induce cytochrome P450, causing significant drug interactions. However, levetiracetam does not induce the P450 system and does not exhibit any relevant drug interactions. Intravenous delivery is as bioavailable as the oral medication allowing it to be used in emergency situations. Levetiracetam is an attractive option for brain tumor patients suffering from seizures, but also can be used prophylactically in patients with brain tumors, or patients undergoing neurological surgery. Emerging studies have also demonstrated that levetiracetam can increase the sensitivity of Glioblastoma tumors to the chemotherapy drug temozolomide. Levetiracetam is a safe alternative to conventional antiepileptic drugs and an emerging tool for brain tumor patients combating seizures.
Traumatic brain injury (TBI) can cause seizures and the development of epilepsy. The incidence of seizures varies from 21% in patients with severe brain injuries to 50% in patients with war-related penetrating TBI. In the acute and sub-acute periods following injury, seizures can lead to increased intracranial pressure and cerebral edema, further complicating TBI management. Anticonvulsants can be used for seizure prophylaxis according to the current Parameters of Practice and Guidelines in a subset of severe TBI patients, and for a limited time window. Phenytoin is the most widely prescribed anticonvulsant in these patients. Intravenous levetiracetam, made available in 2006, is now being considered as a viable option in acute care settings if phenytoin is unavailable or not feasible due to side-effects. We discuss current data regarding the role of intravenous levetiracetam in seizure prophylaxis of severe TBI patients and the need for future studies.
Intractable epilepsy in children poses a serious medical challenge. Acute repetitive seizures and status epilepticus leads to frequent emergency room visits and hospital admissions. Delay of treatment may lead to resistance to the first-line anticonvulsant therapies. It has been shown that these children continue to remain intractable even after acute seizure management with approved Food and Drug Administration (FDA) agents. Intravenous levetiracetam, a second-generation anticonvulsant was approved by the FDA in 2006 in patients 16 years and older as an alternative when oral treatment is not an option. Data have been published showing that intravenous levetiracetam is safe and efficacious, and can be used in an acute inpatient setting. This current review will discuss the recent data about the safety and tolerability of intravenous levetiracetam in children and neonates, and emphasize the need for a larger prospective multicenter trial to prove the efficacy of this agent in acute seizure management.
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