Maternal blood samples were collected at delivery, from the umbilical cord, and 2 days after delivery, blood samples were obtained from the newborns. Breast milk and plasma were collected from 11 mothers and their suckling infants after birth to determine LEV concentration. Neonatal plasma LEV concentration had an estimated half-life of 18 h. The LEV dose in infants was estimated to 2. There appears to be enhanced elimination of LEV in pregnancy. The resulting significant decline in plasma concentration indicates that therapeutic monitoring in pregnancy may be valuable Weinstock and colleagues assessed tolerability, safety, and pharmacokinetics of IV LEV in 52 children with epilepsy in a prospective, single-arm, multicenter study.
Children with difficult venous access, EKG abnormalities, ketogenic diet, felbamate exposure within 18 months, and status epilepticus in the previous 3 months were excluded. On study day 1, LEV pharmacokinetic assessments were performed from blood and saliva at 3—10 min intervals after the start of the infusion, at the end of the infusion, and up to 12 h post-infusion. Sixty-three percent of patients had mild to moderate treatment-emergent adverse events. These were most frequently pyrexia and dry mouth.
The LEV plasma and saliva concentration ranges were at expected levels based on the administered dose. The researchers concluded that IV LEV in the acute setting was overall well tolerated in children 1 month to 16 years Merhar and colleagues enrolled neonates in a prospective study to determine the pharmacokinetics of LEV. Before the first dose of LEV was administered, blood draws were taken. Fifty-four total measurements of LEV blood levels were obtained at time points during the entire dosing interval and concentrations were quantified by a liquid chromatography—electrospray tandem mass spectrometry assay.
The pharmacokinetic analyses were performed with non-linear mixed effects modeling. The initial loading doses of LEV were between The model prediction of the median maximum drug concentration was LEV was well tolerated in this population. The only adverse effect observed was mild somnolence 24 h after LEV administration. Thus, Merhar and colleagues concluded that the pharmacokinetics of LEV in neonates differed from children and adults Ten minutes after the infusion, a blood level of LEV was drawn. Seizure types, duration, frequency, and seizure outcomes were evaluated via hospital chart review.
There were no observations of serious adverse reactions, although sleepiness, fatigue, and restlessness were noted. All seizure types had an apparent decrease in seizure frequency from 24 h before compared to 24 h after the infusion. Ng and colleagues reported In addition, The authors also reported that Glauser and colleagues also conducted a multicenter, open label, single-dose pharmacokinetic study to assess LEV and its major metabolite L in infants and young children who were diagnosed with epilepsy.
Thirteen subjects were enrolled in the study with the age range between 2. One patient was excluded because of a medical condition. The samples were collected predose and at 1, 2, 4, 9, 12, 16, and 24 h. The half-life of LEV was found to be 5. No serious side-effects were reported.
The authors concluded that the mean half-life of the drug was shorter and clearance was much more rapid as compared to previously reported adult data. The authors suggested that larger doses of the drug, which are corrected for body weight, should be administered to infants and young children Otoul and colleagues studied children aged 4—16 years with epilepsy being treated with adjunctive LEV to determine whether plasma concentration of carbamazepine, valproic acid, topiramate, and lamotrigine were affected.
There were 95 males and 92 females with 94 subjects randomized to receive adjunctive treatment with LEV and 93 subjects receiving placebo. Blood samples were taken at each study visit for trough AED levels and LEV levels, including two to three baseline period visits and five visits over the evaluation period.
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At baseline and during LEV treatment the geometric mean concentrations were carbamazepine 8. When LEV was compared to placebo, no differences were observed. The researchers concluded that in children with epilepsy LEV does not affect plasma concentrations of carbamazepine, valproic acid, topiramate, or lamotrigine Study subjects were healthy besides being diagnosed with epilepsy and were aged 18—65 years. Patients were excluded if they were pregnant. The 15 subjects included in the EIAED group were stable for at least 1 month of treatment with carbamazepine, phenytoin, or phenobarbital alone or in combination.
The 15 subjects in the control group were matched patients not receiving AEDs. Subjects on valproate or other drugs influencing drug metabolism were excluded. At baseline and at frequent intervals, serum and urine LEV levels were measured after a single oral 1, mg dose.
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There were no reports of adverse effects related to LEV doses. The conclusion was that this interaction could have clinical significance for some patients even though the magnitude of the effect was relatively modest Intravenous levetiracetam is an effective AED for seizure control. As early treatment either pretreatment with benzodiazepines or nothing in 14 of the patients, IV LEV showed an efficacy of The use of IV LEV in neonates resulted in favorable efficacy and tolerability as described by Abend and colleagues 22 , Khan and colleagues 23 , and Michaelides et al 24 in a variety of seizure etiologies.
Furwentsches and colleagues 25 and Ramantani and colleagues 26 have also demonstrated LEV efficacy in prospective studies in which LEV was used as a first line treatment. Li et al 27 also demonstrated that LEV is a safe and effective treatment for infants and children in an observational, prospective study.
Kirmani and colleagues 28 , Goraya and colleagues 29 , and Gallentine and colleagues 30 also showed the efficacy of LEV in acute seizure management in children. However, IV LEV is not approved for status epilepticus because no randomized larger multicenter trials were done to evaluate the efficacy in status epilepticus. Levetiracetam can be used for both partial and generalized epilepsies but limitations in terms of seizure types have been published in the form of case reports and retrospective case series.
LEV has been reported to be associated with aggravation of myoclonus in children and with adolescents with juvenile myoclonic epilepsies 34 , Caraballo and colleagues reported data which revealed LEV induced worsening of seizures during continuous spikes and waves during slow sleep in children with refractory epilepsies Similar data about increased frequency of absence seizures with LEV have also been reported in the literature The most common side-effects of LEV are neurobehavioral, including fatigue, nervousness, generalized weakness, irritability, agitation, emotional lability, depression, mood swings, vertigo, anxiety, unsteadiness, seizures, memory loss, confusion, increased reflexes, paresthesias, aggression, cognitive decline, and increased risk of suicide 1 , Other common side-effects include hypersensitivity reactions, infections, myalgias, rhinitis, and anorexia 1.
Neurobehavioral side-effects are the main cause of discontinuing the medications in most instances There are several case reports and case series which report acute onset of psychosis with the initiation of LEV 39 — Increased risk of suicide has also been reported in patients on LEV therapy 42 , Levetiracetam is a novel AED which is approved as adjunctive therapy for partial-onset seizures both in adults and children 1 month and older.
The metabolism of LEV has no effect on the cytochrome P enzyme system so it is favorable in terms of no drug—drug interactions. No dose adjustment is needed in hepatic impairment but dose needs to be adjusted in patients with renal impaired. No tolerance was observed and efficacy was maintained in long term studies. The drug seems to be well-tolerated in pregnancy and teratogenic potential is less than first generation antiepileptics. The anticonvulsant levels seem to decline toward the latter part of pregnancy requiring close monitoring of the drug levels.
The most common side-effects are somnolence, dizziness, and asthenia.
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The other reported side-effects are irritability, agitation, aggressive behavior, and anger. The intravenous formulation is approved for patients 16 years or older if oral administration of the drug is not feasible. However, the off — label use in adults and children for acute seizure management yielded favorable results. Further studies are needed to prove the efficacy of this drug for acute seizure management.
The literature shows that LEV has a novel mechanism of action and unique pharmacokinetic profile to be used as a desirable antiepileptic choice in an acute inpatient setting. Our conclusions, on the other hand, are based on existing data which include case reports, case series, retrospective studies, and some prospective trials. However, there are limitations in that there are neurobehavioral side-effects of the drug. We believe that there is a need for larger, prospective, multicenter, randomized double comparative blind trials in order to further clarify the role of this anticonvulsant in acute seizure management.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Keppra Injection Levetiracetam Package Insert. Patsolos PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet 43 — CrossRef Full Text. Towards better brain management: nootropics. Curr Med Chem 14 — Adjunctive levetriacetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study.
Epilepsia 53 —9. Intravenous levetiracetam in critically ill children with status epilepticus or acute repetitive seizures. Pediatr Crit Care Med 10 — Trinka E, Dobesberger J. New Treatment options in status epilepticus: a critical review on intravenous levetiracetam.
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J Child Neurol 24 — Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis Child-Pugh classes A, B, and C : characterization by dynamic liver function tests. Clin Pharmacol Ther 77 — Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period and lactation. Epilepsia 48 —6. Prospective open-label, single-arm, multicenter, safety, tolerability, and pharmacokinetic studies of intravenous levetiracetam in children with epilepsy. J Child Neurol 28 —9. Pharmacokinetics of levetiracetam in neonates with seizures.
J Pediatr —4. Intravenous levetiracetam in children with seizures: a prospective safety study. J Child Neurol 25 —5. Pharmacokinetics of levetiracetam in infants and young children with epilepsy. Epilepsia 48 — Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topiramate, and lamotrigine in children with epilepsy. Epilepsia 48 —5. Influence of enzyme inducing antiepileptic drugs on the pharmacokinetics of levetiracetam in patients with epilepsy. Epilepsy Res 94 — Efficacy of intravenous levetiracetam as an add-on treatment in status epilepticus: a multicentric observational study.
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Pediatr Neurol 44 —9. Tolerability and dosing experience of intravenous levetiracetam in children and infants. Epilepsy Res 81 —7. Medical Oncology. Medical Toxicology. Pain Medicine. Palliative Medicine. Rehabilitation Medicine. Respiratory Medicine and Pulmonology. Sleep Medicine. Sports and Exercise Medicine. Oral and Maxillofacial Surgery. Paediatric Dentistry. Restorative Dentistry and Orthodontics. Surgical Dentistry. Clinical Skills. Communication Skills. Nursing Skills.
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