A Review of Anti-Seizure Drug Levetiracetam

Epilepsy is a permanent disorder in the brain that causes seizures. An estimated 5 million Americans have been diagnosed with epilepsy.[1] There is no cure for epilepsy, but many drugs have been approved by the Food and Drug Administration (FDA) to control the condition by preventing seizures. This article reviews the safety and effectiveness of one of these drugs, levetiracetam (KEPPRA, ROWEEPRA, SPRITAM), and its long-acting variant, levetiracetam extended-release (KEPPRA XR).

Seizures and epilepsy

A seizure is caused by a sudden misfiring of electrical activity by multiple brain cells at the same time.[2] Not everyone who has a seizure has epilepsy. A person can have one or more seizures due to a temporary cause, such as fever, infection, medications, alcohol or other toxic exposures, brain tumor or stroke. If this temporary cause is addressed, the seizures usually go away.

Patients who have a seizure for the first time are given a series of tests to determine the cause. Patients also undergo a test known as an electroencephalogram, or EEG, which often can detect abnormal electrical activity in the brain that indicates the potential for seizures. Epilepsy is diagnosed if a person has two or more seizures without a curable cause.[3]

There are two main types of seizure. Generalized seizures affect both sides of the brain, with patients becoming stiff, shaking uncontrollably, experiencing sudden muscle jerks (known as myoclonic seizures), rapidly blinking or staring into space, and sometimes losing consciousness. Partial seizures, also known as focal seizures, affect just one area of the brain and result in confusion or unusual movements or sensations in specific parts of the body. Partial seizures can spread within the brain and become generalized seizures.

Levetiracetam is approved to treat epilepsy only as an add-on medicine in combination with another anti-epileptic drug.[4] It is specifically approved to treat partial seizures, generalized seizures and myoclonic seizures in patients with a seizure disorder known as juvenile myoclonic epilepsy. Levetiracetam extended-release is approved only as an add-on medicine to treat partial seizures.[5]

Levetiracetam effectiveness

As an add-on medicine to another anti-epileptic drug, levetiracetam is effective in further reducing seizure occurrence in patients with both partial and generalized seizures.[6],[7] In clinical trials, over a third of subjects with partial seizures that were persisting even on one or more other drugs experienced at least a 50 percent decrease in the number of seizures after being given levetiracetam, compared with just a tenth of subjects given a placebo.[8] And although the trials in generalized seizures were small, significantly more subjects given levetiracetam as add-on therapy achieved freedom from seizures during the trials than those given a placebo.[9]

Levetiracetam safety

A large review of clinical trial data found that levetiracetam is associated with nervousness and irritability, sleepiness, fatigue and dizziness.[10] In addition to these side effects, levetiracetam’s label warns of other behavioral abnormalities, such as aggression, anger, emotional instability and, less often, psychotic symptoms such as paranoia.[11] The drug’s label also warns of suicidal thoughts and behavior, potentially life-threatening skin reactions, lack of coordination and difficulty walking, abnormal blood cell counts, lower blood levels of the drug during pregnancy and, in young children, an increase in blood pressure. Withdrawing levetiracetam suddenly might provoke a seizure.

What You Can Do

Seek immediate medical attention if you have a seizure or if you witness someone having a seizure. Tests can determine whether a seizure is due to a temporary cause or whether epilepsy is present.

If you have epilepsy, levetiracetam is an effective treatment only if your seizures persist even after having taken one or more other anti-seizure drugs. For this reason, we list levetiracetam as a Limited Use drug.

You should use levetiracetam extended-release only if you have partial seizures, as it is not approved for any other type of seizure.

If you are pregnant, your doctor will have to carefully monitor you to ensure that your dose of levetiracetam is high enough to be effective.

References

[1] Centers for Disease Control and Prevention. Epilepsy fast facts. https://www.cdc.gov/epilepsy/basics/fast-facts.htm. Accessed February 6, 2017.

[2] Johns Hopkins Medicine. Neurology and neurosurgery. Seizures. http://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/epilepsy/seizures/. Accessed February 6, 2017.

[3] Ibid.

[4] UCB Inc. Label: levetiracetam (KEPPRA). October 2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021035s096,021505s036lbl.pdf. Accessed February 6, 2017.

[5] UCB Inc. Label: levetiracetam extended-release (KEPPRA XR). October 2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022285s023lbl.pdf. Accessed February 6, 2017.

[6] Otoul C, Arrigo C, van Rijckevorsel K, French JA. Meta-analysis and indirect comparisons of levetiracetam with other second-generation antiepileptic drugs in partial epilepsy. Clin Neuropharmacol. 2005;28(2):72-78.

[7] Fang Y, Wu X, Xu L, et al. Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types. J Clin Neurosci. 2014;21(1):55-62.

[8] Otoul C, Arrigo C, van Rijckevorsel K, French JA. Meta-analysis and indirect comparisons of levetiracetam with other second-generation antiepileptic drugs in partial epilepsy. Clin Neuropharmacol. 2005;28(2):72-78.

[9] Fang Y, Wu X, Xu L, et al. Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types. J Clin Neurosci. 2014;21(1):55-62.

[10] Verrotti A, Prezioso G, Di Sabatino F, Franco V, Chiarelli F, Zaccara G. The adverse event profile of levetiracetam: A meta-analysis on children and adults. Seizure. 2015;31:49-55.

[11] UCB Inc. Label: levetiracetam (KEPPRA). October 2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021035s096,021505s036lbl.pdf. Accessed February 6, 2017.