Levetiracetam, sold under the brand name Keppra among others, is an anti-seizure medication (medication) used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures, and is taken either by mouth as an immediate or extended release formulation or by injection into a vein. Common side effects of levetiracetam include sleepiness, dizziness, feeling tired, and aggression. Severe side effects may include psychosis, suicide, and allergic reactions such as Stevens–Johnson syndrome or anaphylaxis. Levetiracetam is the S-enantiomer of etiracetam. It acts as a synaptic vesicle glycoprotein 2A (SV2A) ligand. Levetiracetam was approved for medical use in the United States in 1999 and is available as a generic medication. In 2023, it was the 101st most commonly prescribed medication in the United States, with more than 6 million prescriptions. It is on the World Health Organization's List of Essential Medicines and among the most commonly prescribed anti-seizure medications in the world.
Medical uses
Focal epilepsy Levetiracetam is effective as single-drug treatment for newly diagnosed focal epilepsy in adults. It reduces focal seizures by 50% or more as an add-on medication.
Partial-complex epilepsy Levetiracetam is effective as an add-on treatment for partial (focal) epilepsy.
Generalized epilepsy Levetiracetam is effective for the treatment of generalized tonic-clonic epilepsy. It has been approved in the United States as an add-on treatment for 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 is sometimes used as off-label treatment for status epilepticus.
Prevention of seizures Based on low-quality evidence, levetiracetam is about as effective as phenytoin for the prevention of early seizures after traumatic brain injury. It may be effective for prevention of seizures associated with subarachnoid hemorrhages.
Other 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 developmental disorders within the autism spectrum, with studies finding it effective only in the setting of partial, myoclonic, or tonic-clonic seizures associated with autism spectrum disorder.
Pregnancy Levetiracetam is considered to be one of the safest anti-seizure medications during pregnancy. Studies show rates of birth defects that are similar to patients who are not taking an anti-seizure medication.
Special groups Levetiracetam's efficacy and tolerability in individuals with intellectual disability is comparable to those without. 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 disorders of the central nervous system. Levetiracetam is the most commonly prescribed initial antiepileptic drug in children aged 1–36 months. One study found 66% of participants to be seizure-free after an average of 12 months on levetiracetam, a relatively high percentage compared to other antiepileptics.
Adverse effects The most common adverse effects of levetiracetam treatment include effects on the central nervous system such as somnolence, decreased energy, headache, dizziness, mood swings 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 occur mostly within the first month of therapy, but can rarely develop at any time during treatment. Although rare, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which present as a painful, spreading rash with redness, 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. In a study, the incidence of decreased bone mineral density in patients on levetiracetam was significantly higher than for those on different epileptic medications.
Suicide Levetiracetam, along with other anti-epileptic drugs, can increase the risk of suicidal behavior or thoughts. Patients taking levetiracetam should be monitored closely for signs of worsening depression, suicidal thoughts or tendencies, or any altered emotional or behavioral states.
Kidney and liver Kidney impairment decreases the rate of elimination of levetiracetam from the body. Individuals with reduced kidney function may require dose adjustments, guided by monitoring of kidney function. Dose adjustment of levetiracetam is not necessary in liver impairment.
Drug interactions 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, ethinylestradiol, or warfarin.
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