Levetiracetam

Keppra is the brand name used in the United States, Canada, the UK, Australia, and some other countries for levetiracetam. The United States Food and Drug Administration (FDA) approved Keppra in 1999 for adjunctive therapy for partial-onset seizures in adult patients with epilepsy.

Keppra
Tablet
Keppra 250mg

250-mg (blue, oblong, scored)
Tablets marked with “ucb” and “250” on one side.

Keppra 500mg

500-mg (yellow, oblong, scored)
Tablets marked with “ucb” and “500” on one side.

Keppra 750mg

750-mg (orange, oblong, scored)
Tablets marked with “ucb” and “750” on one side.

Keppra 1000mg

1000-mg (white, oblong, scored)
Tablets marked with “ucb” and “1000” on one side

Liquid Solution
Keppra Solution

100 mg/mL (clear, colorless, grape-flavored)
The liquid Keppra solution was approved by the FDA in 2003.

Liquid Injection
Keppra Injection Vial

100 mg per 1 mL (milliliters).

Approved by the FDA in 2006, this is an alternative for patients when oral administration is temporarily not feasible; it must be diluted prior to use as per the package insert and administered as a 15-minute intravenous infusion.

Roweepra

Indications

Keppra is approved as adjunctive therapy to treat partial-onset seizures in patients aged 4 years or older with epilepsy, as adjunctive therapy in treating myoclonic seizures in patients aged 12 years or older with juvenile myoclonic epilepsy, and as adjunctive therapy for primary generalized tonic-clonic seizures in patients 6 years of age and older with idiopathic generalized epilepsy.

Forms

Keppra is sold in the United States by UCB Pharma, Inc. This description applies to the U.S. version:

Dosing

Please see package insert.

How to take and store Levetiracetam?

Levetiracetam can be taken with or without food.

Most people prefer to swallow the tablets whole to avoid their bitter taste. People who are unable to swallow whole tablets can crush the tablet and mix it with food. Crushed tablets can also be given to patients who are fed by means of a tube.

The liquid solution of levetiracetam (approved by the FDA in July 2003) should eliminate the need for most tablet-crushing. Always use an accurate measuring spoon or syringe to make sure the amount is correct. Do not use a regular teaspoon.

Keppra should be stored at room temperature, away from humidity and light.

Missed Doses

In general, tell patients that if they forget a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should delay that dose for a few hours instead of taking two doses very close together.

Patients who often forget doses may benefit from using a special pillbox or watch with an alarm.

Clinical Pharmacology of Levetiracetam

Absorption: Levetiracetam is rapidly and nearly completely absorbed after oral administration. Peak serum concentrations with both the tablets and liquid form are achieved in about 1 hour when levetiracetam is taken without food and 2 hours with food. Daily doses and plasma concentrations are linearly related.

Distribution and metabolism: Levetiracetam is not protein bound (<10%) and the major metabolic pathway is hydrolysis of the acetamide group to the inactive carboxylic derivative.

Steady state: In children and adults, steady state is achieved after two days of twice-daily dosing.

Efficacy of Levetiracetam

In a number of randomized, controlled clinical trials, Lvetiracetam (at doses of 1000 to 3000 mg/day) has been significantly more effective than a placebo for patients with frequent partial seizures. Between 21% and almost 40% of the patients who took levetiracetam as add-on therapy reduced their seizure frequency by half or more, without excessive adverse side effects (Shorvon et al. 2000). The rate of side effects was lower than reported for most other seizure medicines.

At least one study has found that levetiracetam also may be effective when used alone to treat partial seizures (Ben-Menachem & Falter, 2000). Levetiracetam was first given as add-on therapy, and the other antiepileptic medications were gradually withdrawn from patients whose seizure frequency was reduced by at least half. More than half of these patients continued at least a 50% reduction in seizure frequency with levetiracetam alone.

Common side effects of Levetiracetam

Dose-related side effects: In clinical studies performed before its approval by the FDA, Keppra (levetiracetam) was given to 769 patients who were already taking another seizure medicine, and only 15% of them stopped taking Keppra or lowered their dosage because of side effects, compared to 11.9% of the 439 patients who received a placebo. More recent studies have shown similar numbers and Keppra has now been used by at least 100,000 patients. It continues to have an excellent safety profile.

The side effects that were reported more frequently with Keppra than with placebo during the clinical trials were:

  • sleepiness
  • asthenia (loss of strength and energy)
  • dizziness
  • infection

These occurred mostly during the first 4 weeks of treatment. The infections were mainly colds (upper respiratory infections) and infection has not been a problem during recent experience with large numbers of patients.

Some other side effects mentioned even less often have included:

  • Agitation
  • Anxiety
  • Other mood changes
  • Coordination difficulties
  • Headache
  • Some doctors have observed behavioral problems. These were more frequent in children than in adults.
Serious Side effects of Levetiracetam

Side effects in most patients are mild. Anxiety and agitation can present problems to patients or their families. Psychosis occurs rarely.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an anti-epileptic drug (AED). The FDA advisory panel voted to accept the FDA's data at its meeting on July 10.

  • Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions.
  • Do not make any changes to the medication regimen without first talking with the responsible healthcare professional.
  • Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
  • Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:
    • Talking or thinking about wanting to hurt yourself or end your life
    • Withdrawing from friends and family
    • Becoming depressed or having your depression get worse
    • Becoming preoccupied with death and dying
    • Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

Other Uses of Levetiracetam

Some evidence suggests efficacy against photosensitive epilepsy and myoclonic seizures.

Levetiracetam Contraindications

The only patients for whom levetiracetam is contraindicated are those who are allergic to levetiracetam or any of its inactive ingredients.

Because it is mostly excreted by the kidneys, caution should be exercised when prescribing levetiracetam for patients with renal dysfunction.

Levetiracetam Interactions with other medications

Effects of levetiracetam on other drugs: Levetiracetam does not act as an inducer or inhibitor of the hepatic cytochrome P450 system or other enzymes; therefore, there is little potential for pharmacokinetic interactions with other drugs, including oral contraceptives.

Effects of other drugs on levetiracetam: Because its metabolism is independent of the hepatic cytochrome P450 system, levetiracetam levels are unaffected by concomitant AEDs.

AED interaction sheets: Seizure drugs are often affected by drug-drug interactions. Print these informative sheets for practical help.

Levetiracetam effects on Children

In children, levetiracetam primarily has been used to treat partial seizures. Children usually start with 10 mg/kg per day, given in two doses. This amount can be titrated gradually to about 20-40 mg/kg per day, in two doses.

Levetiracetam and Pregnancy

The U.S. Food and Drug Administration (FDA) lists levetiracetam in Pregnancy Category C. This indicates that caution is advised, but the benefits of the medication may outweigh the potential risks. Studies in animals have shown some harm to the fetus. There have been no published reports of pregnancy outcomes in levetiracetam-treated women.

The risk of defects is generally higher for women who take more than one anti-epileptic drug (AED) and for women with a family history of birth defects. Advise women who are capable of becoming pregnant to take at least 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent neural tube defects. Women at high risk, such as those with a history of a neural tube defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant. The effectiveness of prophylactic folic acid use in preventing defects related to levetiracetam has not been proven, however, so diagnostic ultrasonography at the 18th to 20th week is recommended, especially if pregnancy termination is an option.

About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how their AED is handled by the body. Whether this applies to levetiracetam is not yet known, so blood levels during pregnancy may help determine if the dosage needs to be adjusted.

Keppra is excreted in breast milk. According to the package insert, because of the potential for serious adverse reactions in nursing infants from Keppra, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Levetiracetam effects on Seniors

Patients over age 65 or 70 may have age-related reductions in kidney function that could reduce excretion and cause problems with toxicity at usual doses. Therefore, lower initial doses, longer intervals between doses, and caution in titration are required. Doses in patients with renal insufficiency should be reduced by 50%.

The lack of interactions between levetiracetam and other medications is an advantage over most other AEDs commonly used by seniors.

Levetiracetam Dosing and titration

Treatment in adults can be initiated at 500 mg twice daily. This was an effective dose in the controlled trials. The dosage can be titrated by 1,000 mg every two weeks, up to 4,000 mg daily as needed for seizure control.

Doses in patients with renal insufficiency should be reduced by 50%.

Therapeutic blood levels have not been established. Dosage adjustments should depend on clinical response.

Levetiracetam Package insert

In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a “package insert” because it is usually included with each package of the medicine.

You can also read these documents (also called "prescribing information") online. The U.S. package insert for Keppra (levetiracetam) is found at:

Some of the information may differ in other countries.

Learn how to read a package insert here.

Levetiracetam References for Professionals

Abstracts of articles relevant to this topic are available through PubMed, a service of the National Library of Medicine.

Here are links to some articles relevant to this subject:

Shorvon SD, Lowenthal A, Janz D, et al. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group. Epilepsia 2000 Sep;41(9):1179-86. PMID: 10999557.

Ben-Menachem E, Falter U. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group. Epilepsia 2000 Oct;41(10):1276-83. PMID: 11051122.

Cramer JA, Ben Menachem E, French J. Review of treatment options for refractory epilepsy: new medications and vagal nerve stimulation. Epilepsy Res 2001 Nov;47(1-2):17-25. PMID: 11673017."

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