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Levetiracetam is an anticonvulsant medication used to treat epilepsy. It is the S-enantiomer of etiracetam, structurally similar to the prototypical nootropic drug piracetam.

Levetiracetam is marketed under the trade name Keppra. Keppra is manufactured by UCB Pharmaceuticals Inc. Since November 2008, the drug is available as a generic brand in the United States and the United Kingdom.

Medical uses
Levetiracetam has been approved in the European Union as a monotherapy treatment for epilepsy in the case of partial seizures, or as an adjunctive therapy for partial, myoclonic and tonic-clonic seizures. It is also used in veterinary medicine for similar purposes.

Levetiracetam has potential benefits for other psychiatric and neurologic conditions such as Tourette syndrome, autism, and anxiety disorder, as well as Alzheimer's disease. However, due to possible adverse effects, its benefit-risk ratio in these conditions is not well understood.

Along with other anticonvulsants like gabapentin, it is also sometimes used to treat neuropathic pain. It has not been found to be useful for essential tremors.

Mechanism of action
The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. However, the drug binds to a synaptic vesicle glycoprotein, SV2A, and inhibits presynaptic calcium channels reducing neurotransmitter release and acting as a neuromodulator. This is believed to impede impulse conduction across synapses.

Adverse effects
The most common adverse effects of levetiracetam treatment include CNS effects such as somnolence, infection, asthenia, headache, dizziness, and ataxia. These adverse effects are most pronounced in the first month of therapy. About 4% of patients dropped out of pre-approval clinical trials due to these side effects.

About 13% of people taking levetiracetam experience adverse neuropsychiatric symptoms, which are usually mild. These include including agitation, hostility, apathy, anxiety, emotional lability, and depression. Serious psychiatric adverse side effects that are reversed by drug discontinuation occur in about 1%. These include hallucinations, suicidal ideations, or psychosis. These occurred mostly within the first month of therapy, but they could develop at any time during treatment.

A study published in 2005 suggests that the addition of pyridoxine (vitamin B6) may curtail some of the psychiatric symptoms.

Although rare, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with levetiracetam. Recommendations are to discontinue leviteracetam upon signs of unexplained rash. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. The incidence of SJS following exposure to anti-epileptics such as Levetiracetam is about 1 in 3,000

Warnings
Levetiracetam, along with other anti-epileptic drugs, can increase the risk of suicide behavior or ideation. Patients taking levetiracetam should be monitored closely for signs of worsening depression, suicidal thoughts or tendencies, or any altered emotional or behavioral states. [10]

Levetiracetam should not be used in patients who have previously shown hypersensitivity to levetiracetam or any of the inactive ingredients in the tablet or oral solution. Such hypersensitivity reactions include, but are not limited to, unexplained rash with redness or blistered skin, difficulty breathing, and tightness in the chest or airways. [11]

Drug interactions
No significant pharmacokinetic interactions were observed between levetiracetam or its major metabolite and concomitant medications. The pharmacokinetic profile of Keppra is not influenced by phenytoin, phenobarbital, primidone, carbamazepine, valproic acid, lamotrigine, gabapentin, digoxin, oral contraceptives ethinylestradiol, and warfarin.

Pregnancy
Levetiracetam is a Pregnancy Category C Drug. Studies in female pregnant rats have shown minor fetal skeletal abnormalities when given maximum recommended human doses of Keppra orally throughout pregnancy and lactation.

A study in the Journal Neurology retrospectively looked at 671 human pregnancies with known maternal exposure to levetiracetam and found that the rate of Major congenital malformations (MCM) was not significantly higher when levetiracetam was used as a monotherapy. However, the majority of the patients were also exposed to other anti-epileptic drugs as a combination therapy and found increases in Major Congential Malformations when combined with valproate and carbamazepine. The paper concluded that the data suggests levetiracetam monotherapy to be a suitable regimen if anti-epileptic medication is needed during pregnancy.

Elderly
Studies were conducted to look for increased adverse effects in the elderly population as compared to younger patients. One such study published in Epilepsy Research showed no significant increase in incidence of adverse symptoms experience by young and elderly patients with CNS disorders.

Children
No established safety and efficacy for use in patients under 4 years of age. Animal studies in juvenile rats and dogs did not indicate a potential for age-specific toxicity.

Assay of levetiracetam
There are only a few papers published reporting therapeutic drug monitoring methods of levetiracetam. Three of them employed HPLC with UV-detection, and two methods were using GC with NPD-detection. Microemulsion electrokinetic chromatography with UV-detection was utilized in one method. Two methods facilitating chiral separation of the S- and R- enantiomer of levetiracetam, one utilizing GC–MS and the other HPLC–UV, were published. These methods were designed to investigate in dogs the pharmacokinetic and pharmacodynamic properties of the two enantiomers separately. For routine therapeutic drug monitoring in men, these methods were not appropriate. In all but one of the methods, sample preparation with SPE or liquid–liquid extraction is necessary. Pucci et al. evaluated the feasibility of protein precipitation as the only sample preparation step in comparison to SPE. They concluded, that protein precipitation is a suitable and fast sample preparation for measuring routine patient samples. Mecarelli et al. studied the concentration of levetiracetam in both serum and saliva of patients with epilepsy.

Various HPLC,      and LC-MS,   methods have been reported for the determination of levetiracetam in pure and pharmaceutical dosage forms.

Available forms
Avaliable as intravenous and oral formulations.

In 2015 Aprecia’s 3d-printed form of the drug was approved by the FDA.