Levetiracetam XR

Keppra XR 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 XR in 2008 for adjunctive therapy for partial-onset seizures in adult patients with epilepsy.

Keppra XR
Tablet
Keppra-XR 500mg

500-mg
(white, film-coated tablet, imprinted with "UCB 500XR" in red on one side)

Keppra-XR 750mg

750-mg
(white, film-coated tablet, imprinted with "UCB 750XR" in red on one side)

Keppra XR is not available in generic (non-brand name) form.

Indications

Keppra XR is approved as adjunctive therapy to treat partial-onset seizures in patients aged 16 years or older with epilepsy.

Forms

Keppra XR is sold in the United States by UCB Pharma, Inc. The name or appearance may be different in various countries, but the dose (measured in milligrams, abbreviated "mg") usually will be the same. This description applies to the U.S. version:

Dosing

Please see package insert.

How to take and store Levetiracetam XR?

Keppra XR can be taken with or without food.

Keppra XR tablets must be swallowed whole. They should not be chewed, broken, or crushed.

Keppra XR 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, instruct them on whether they should delay that dose for a period of 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.

Mechanisms of actions of Levetiracetam XR

The mechanism of action of Keppra XR is still under investigation. It appears to be different from that of other antiepileptic drugs.

Clinical Pharmacology of Levetiracetam XR

The bioavailability of Keppra XR is similar to that of the immediate release Keppra tablets. Plasma half-life of Keppra XR is approximately 7 hours.

Absorption
Keppra XR is rapidly and nearly completely absorbed after oral administration. Peak serum concentrations Keppra XR are achieved in about 4 hours. Daily doses and plasma concentrations are linearly related in doses tested up to 3,000 mg/day.

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

Efficacy of Levetiracetam XR

In a number of randomized, controlled clinical trials, immediate release Keppra (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 Keppra 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 Keppra also may be effective when used alone to treat partial seizures (Ben-Menachem & Falter, 2000). Keppra 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 Keppra alone.

Common side effects of Levetiracetam XR

Dose-related side effects
In clinical studies performed before its approval by the FDA, immediate relase 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. Keppra 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 XR

Experience with immediate release Keppra suggests that 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 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 XR

While Keppra XR is approved as adjunctive therapy in the treatment of partial onset seizures in patients 16 years of age or older with epilepsy, immediate release 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.

Levetiracetam XR Contraindications

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

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

Levetiracetam XR Interactions with other medications

Effects of Keppra XR 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 Keppra XR
Because its metabolism is independent of the hepatic cytochrome P450 system, Keppra XR 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 XR effects on Children

In children, immediate release Keppra 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. Note that the lowest available strength of Keppra XR is 500 mg, and that Keppra XR is not approved for children under the age of 16.

Levetiracetam XR and Pregnancy

The U.S. Food and Drug Administration (FDA) lists Keppra XR 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 Keppra XR-treated women.

The risk of defects is generally higher for women who take more than one 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 Keppra XR 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 Keppra XR is not yet known, so blood levels during pregnancy may help determine if the dosage needs to be adjusted.

Keppra XR is excreted in breast milk. According to the package insert, because of the potential for serious adverse reactions in nursing infants from Keppra XR, 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 XR 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 Keppra XR and other medications is an advantage over most other AEDs commonly used by seniors.

Levetiracetam XR Dosing and titration

Treatment in adults can be initiated at 1000 mg once daily. The dosage can be titrated by 1,000 mg every two weeks, up to 3,000 mg daily as needed for seizure control.

Doses in patients with renal insufficiency should be reduced by 50%. Patients on renal dialysis should be given immediate release Keppra.

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

Levetiracetam XR 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 XR (levetiracetam) is found at:

Some of the information may differ in other countries.

To learn how to read and understand a package insert, see How to read a package insert.

Levetiracetam XR 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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