Adverse Effect Of Levetiracetam Research Articles

Levetiracetam as the First-line Antiepileptic in Neonatal Seizures

Background: The quest persists for an ideal newer antiepileptic drug (AED) with better efficacy and tolerability. Levetiracetam (LEV) is one of these AEDs with a novel mechanism of action, good pharmacokinetic profile, acceptable tolerability, and side-effect profile. The present study assessed the safety and efficacy of intravenous levetiracetam as a first-line AED in neonatal seizures.Methods: This prospective observational study was conducted on all term neonates with seizures admitted to the Neonatal Intensive Care Unit (NICU) of a tertiary care center. Neonates with hypoglycemia, hypocalcemia, hypomagnesemia, inborn errors of metabolism, or those who received other AEDs prior to admission were excluded from the study. 20mg/kg Intravenous LEV was administered as first-line AED and graded up to 40mg/kg if seizures were not controlled in 2 h; thereafter, second-line AED was added.Results: Only 36.2% (21/58) of the cases responded to LEV as first-line AED. Hypoxic Ischaemic Encephalopathy(HIE) was the most common etiology of seizures (55.2%). Subtle seizures were most responsive to LEV (60%), while multifocal clonic seizures (22.3%) responded the least. No adverse effect of LEV was observed during the study period.Conclusion: Only 36.2% of the cases responded to LEV as first-line AED, and subtle seizures were the most responsive seizures. Therefore, the efficacy of LEV as first-line AED in neonatal seizures is yet to be proven by a larger study. There were no adverse effects of LEV during the study period indicating the relative safety of this drug.

Psychotic disorders as an adverse effect of levetiracetam or discontinuation of mood stabilising drugs

Patients using antiepileptic drugs (AEDs) suffer from relatively common adverse effects manifested by psychotic and behavioural disorders. This is particularly true in patients with a history of psychiatric disorders and using levetiracetam. This has important therapeutic implications because very often discontinuation of AED is the only available option. Simultaneous use of mood-stabilising AEDs reduces this risk; however, too rapid withdrawal of such AEDs can also induce psychotic symptoms. We present four cases of epilepsy patients who experienced psychiatric disorders induced by LEV. In one of them, they occurred after adding LEV to the treatment; in two – after discontinuation of a mood-stabiliser; and in one both modifications were made simultaneously. Our cases show that LEV-induced behavioural disorders are dose-dependent and do not always require discontinuation of the drug. This seems to be justified by good seizure control ensured by the use of LEV, and using mood-stabiliser reduces LEV adverse effects.

Levetiracetam‐Induced Acute Generalized Exanthematous Pustulosis

Antiepileptic drugs have been associated with many adverse effects, including different types of rashes; however, the frequency of rash varies among the drugs. The most common adverse effects associated with levetiracetam include somnolence, asthenia, headache, dizziness, and behavioral abnormalities. Until recently, rash had not been reported as an adverse effect of levetiracetam in adults. We describe a 45‐year‐old, African‐American woman who developed a desquamating rash after starting levetiracetam for a witnessed seizure. The rash improved after the drug was discontinued, but on rechallenge, the desquamating rash reappeared. The patient was hospitalized, levetiracetam was discontinued, and supportive care and treatment with triamcinolone 0.1% cream and oral prednisone were started. Her rash was biopsied, and she was diagnosed with drug‐induced acute generalized exanthematous pustulosis (AGEP). With topical and oral steroid treatment the patient's rash improved, and she was discharged on hospital day 4. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's development of AGEP and levetiracetam exposure. To our knowledge, this is the first case report of levetiracetam‐induced AGEP. Although levetiracetam is usually well tolerated, clinicians should be aware of this potential adverse drug reaction in patients who develop severe skin reactions while receiving this drug.

Thrombocytopenia as an Adverse Effect of Levetiracetam Therapy in a Child

Levetiracetam is one of the newer anti-epileptic medications, which is now widely used in the treatment of childhood epilepsy. Thrombocytopenia is not a well-known adverse effect of this medication. There have only been two adult case reports describing this feature as an adverse effect of levetiracetam. We describe this feature in a child. A six and half-year-old boy developed symptomatic epilepsy secondary to cerebral venous sinus thrombosis. He was treated with levetiracetam. He made a good recovery from his primary illness, but five weeks after he started taking levetiracetam, he presented with thrombocytopenia requiring platelet transfusion. Extensive investigations for known causes of thrombocytopenia were negative. Withdrawal of levetiracetam led to the resolution of thrombocytopenia. Levetiracetam-induced thrombocytopenia is a rare, but significant adverse effect.

Monotherapy for partial epilepsy: focus on levetiracetam

Levetiracetam (LEV), the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is a recently licensed antiepileptic drug (AED) for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Five randomized, double-blind, placebo-controlled trials enrolling adult or pediatric patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (>/=50% reduction in seizure frequency) of 28%-45%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for 6 months of the study and 8% seizure-free for 1 year. More recent studies illustrated successful conversion to monotherapy in patients with refractory epilepsy, and its effectiveness as a single agent in partial epilepsy. LEV has also efficacy in generalized epilepsies. Adverse effects of LEV, including somnolence, lethargy, and dizziness, are generally mild and their occurrence rate seems to be not significantly different from that observed in placebo groups. LEV also has no clinically significant pharmacokinetic interactions with other AEDs, or with commonly prescribed medications. The combination of effective antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive therapy for partial seizures.

Levetiracetam, Phenytoin, and Valproate Act Differently on Rat Bone Mass, Structure, and Metabolism

Long-term treatment with antiepileptic drugs (AEDs) is associated with increased risk of fractures. Phenytoin (PHT) and valproate (VPA) have both been suggested to influence bone health, whereas levetiracetam (LEV) is scarcely studied. The present study compares the effect of these AEDs on bone mass, biomechanical strength, and bone turnover in rats. Female rats received PHT (50 mg/kg), VPA (300 mg/kg), or LEV (50 and 150 mg/kg) for 90 days. Dissected femurs were analyzed using dual energy x-ray absorptiometry (DXA), three-point cantilever bending, and histomorphological evaluation. Serum levels of biochemical bone turnover markers were monitored using immunoassay quantification. PHT and VPA reduced bone mineral density (BMD) and content (BMC) in one or more bone compartments, whereas LEV did not. VPA induced increased bone turnover, whereas modest changes were observed for PHT. Interestingly, low-dose LEV was associated with reduced biomechanical strength of the femoral neck (mainly trabecular bone). In addition, low-dose LEV treatment resulted in significantly reduced levels of serum osteocalcin, a marker of bone formation. Histomorphological analyses indicated increased retention of cartilage remnants at the growth plate metaphysis of rats treated with low-dose LEV vs. controls. PHT, VPA, and LEV exert differential effects on bone mass and strength, suggesting different mechanisms of action. The weakening effect of low-dose LEV on the femoral neck, despite a constant BMD, suggests a primary effect on bone quality. These findings warrant further human studies of possible adverse effects of LEV on bone development and growth, particularly in children and adolescents.

Clinical experience with levetiracetam in childhood epilepsy: an add-on and mono-therapy trial

We examined the efficacy, optimum dosage and adverse effects of levetiracetam in two prospective trials in children with epilepsy. In the add-on trial, 67 children between 6 months and 16 years were included. In the mono-therapy trial, 10 children between 4 years and 16 years were included. Levetiracetam was titrated up to an optimal dosage for every individual patient, depending on efficacy and tolerability, and reflecting clinical practice. The range of dosages used was between 12 and 62 mg/kg/day, with a median of 33 mg/kg/day. Overall, 20 weeks after the start of levetiracetam, there was a median seizure reduction of 60% (add-on trial 50%; mono-therapy trial 81%). Levetiracetam was equally effective for partial and generalized seizures. Side effects were less common in the mono-therapy trial. Tiredness (7.8%) and aggressiveness (5%) were the most common side effects, and were dose-related, but were no reason to discontinue levetiracetam. In 25% of the children, a positive effect was seen on behaviour and/or alertness. This could not be related directly to seizure control. Overall, these two clinical trials confirm that levetiracetam is a broad spectrum anti-epileptic drug with a favourable safety profile. The positive effect on behaviour needs further quantitative study.

Levetiracetam: a different approach to the pharmacotherapy of epilepsy.

To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of levetiracetam in the treatment of epilepsy. A MEDLINE search restricted to English-language publications was conducted (January 1993-October 2000). Unpublished data provided by the manufacturer and information found in proceedings of professional meetings were also included. DATA EXTRACTION/STUDY SELECTION: Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Only randomized, placebo-controlled clinical trials were included to describe the efficacy and safety of levetiracetam. Levetiracetam is a new antiepileptic drug (AED) that appears to work by a unique mechanism. Animal studies have shown that levetiracetam may prevent epileptogenesis. Levetiracetam is rapidly and completely absorbed, minimally bound to plasma proteins, eliminated through the kidneys, and has a half-life of 6-8 hours. Doses must be adjusted for varying degrees of renal function. In clinical trials, levetiracetam significantly decreased seizure frequency compared with placebo when added to existing AED regimens. One clinical trial indicated that levetiracetam may be effective as monotherapy. Few major adverse effects were reported in the clinical trials; however, several patients reported psychological and psychotic reactions. Levetiracetam is a safe and effective new AED. Its apparent unique mechanism of action makes levetiracetam an important addition to therapy with older medications. Caution should be exercised when administering levetiracetam to individuals who may be prone to psychotic or psychiatric reactions.

Levetiracetam: A Different Approach to the Pharmacotherapy of Epilepsy

OBJECTIVE:To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of levetiracetam in the treatment of epilepsy.DATA SOURCES:A MEDLINE search restricted to English-language publications was conducted (January 1993–October 2000). Unpublished data provided by the manufacturer and information found in proceedings of professional meetings were also included.DATA EXTRACTION/STUDY SELECTION:Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Only randomized, placebo-controlled clinical trials were included to describe the efficacy and safety of levetiracetam.DATA SYNTHESIS:Levetiracetam is a new antiepileptic drug (AED) that appears to work by a unique mechanism. Animal studies have shown that levetiracetam may prevent epileptogenesis. Levetiracetam is rapidly and completely absorbed, minimally bound to plasma proteins, eliminated through the kidneys, and has a half-life of 6–8 hours. Doses must be adjusted for varying degrees of renal function. In clinical trials, levetiracetam significantly decreased seizure frequency compared with placebo when added to existing AED regimens. One clinical trial indicated that levetiracetam may be effective as monotherapy. Few major adverse effects were reported in the clinical trials; however, several patients reported psychological and psychotic reactions.CONCLUSIONS:Levetiracetam is a safe and effective new AED. Its apparent unique mechanism of action makes levetiracetam an important addition to therapy with older medications. Caution should be exercised when administering levetiracetam to individuals who may be prone to psychotic or psychiatric reactions.