|Metabolism||Enzymatic hydrolysis of acetamide group|
|Biological half-life||6–8 hrs|
|Chemical and physical data|
|Molar mass||170.209 g/mol|
|3D model (Jmol)|
|(what is this?)|
Levetiracetam, marketed under the trade name Keppra among others, is a medication used to treat epilepsy. It is used for partial onset, myoclonic, or tonic-clonic seizures. It is the S-enantiomer of etiracetam.
Levetiracetam is available by mouth in two forms: immediate release and extended release. An immediate release tablet has been available as a generic in the United States since November 2008, and in the UK since 2011. The United States patent for the extended release tablet expires September 17, 2028. It was initially patented by UCB Pharma.
- 1 Medical uses
- 2 Adverse effects
- 3 Mechanism of action
- 4 Pharmacokinetics
- 5 Available forms
- 6 See also
- 7 References
- 8 External links
Levetiracetam has been approved in the United States as add-on treatment for partial (focal), myoclonic, and tonic-clonic seizures. 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. Levetiracetam has been shown to reduce partial (focal) seizures by 50% or more as an add-on medication. It is also used in veterinary medicine for similar purposes.
Levetiracetam has potential benefits for other psychiatric and neurologic conditions such as Tourette syndrome, anxiety disorder, and Alzheimer's disease. However, its most serious adverse effects are behavioral, and its benefit-risk ratio in these conditions is not well understood.
Levetiracetam has not been found to be useful for treatment of neuropathic pain, nor for treatment of essential tremors. Levetiracetam has not been found to be useful for treating autism, but is an effective treatment for partial, myoclonic, or tonic-clonic seizures associated with autism spectrum disorder.
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 levetiracetam orally throughout pregnancy and lactation.
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 experienced by young or elderly patients with central nervous system (CNS) disorders.
Levetiracetam may be safely used with caution in children over the age of 4. However, it has not been determined whether it can be safely given to children under the age of 4.
Kidney impairment decreases the rate of elimination of levetiracetam from the body. Individuals with reduced kidney function may require dose adjustments. Kidney function can be estimated from the rate of creatinine clearance.
Dose adjustment of levetiracetam is not necessary in liver impairment.
The most common adverse effects of levetiracetam treatment include CNS effects such as somnolence, decreased energy, headache, dizziness, and coordination difficulties. 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 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 thoughts, or psychosis. These occurred mostly within the first month of therapy, but they could develop at any time during treatment.
Although rare, Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which appears as a painful spreading rash with redness and blistering and/or peeling skin, have been reported in patients treated with levetiracetam. The incidence of SJS following exposure to anti-epileptics such as levetiracetam is about 1 in 3,000.
Levetiracetam should not be used in people 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.
Levetiracetam, along with other anti-epileptic drugs, can increase the risk of suicide behavior or thoughts. People taking levetiracetam should be monitored closely for signs of worsening depression, suicidal thoughts or tendencies, or any altered emotional or behavioral states.
No significant pharmacokinetic interactions were observed between levetiracetam or its major metabolite and concomitant medications. The pharmacokinetic profile of levetiracetam is not influenced by phenytoin, phenobarbital, primidone, carbamazepine, valproic acid, lamotrigine, gabapentin, digoxin, oral contraceptives ethinylestradiol, or warfarin.
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.
The absorption of levetiracetam tablets and oral solution is rapid and essentially complete. The bioavailability of levetiracetam is close to 100 percent, and the effect of food on absorption is minor.
The volume of distribution of levetiracetam is similar to total body water. Levetiracetam modestly binds to plasma proteins (less than 10%).
Levetiracetam does not undergo extensive metabolism, and the metabolites formed are not active and do not exert pharmacological activity. Metabolism of levetiracetam is not by liver cytochrome P450 enzymes, but through other metabolic pathways such as hydrolysis and hydroxylation.
Levetiracetam is eliminated from the body primarily by the kidneys with about 66 percent of the original drug passed unchanged into urine. The plasma half-life of levetiracetam in adults is about 6 to 8 hours.
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