Keppra XR

Partial-Onset Seizures

Keppra XR is primarily used to manage partial-onset seizures. These are seizures that begin in one specific area of the brain rather than affecting the entire brain at once. The medication helps to stabilize electrical activity in the brain to reduce the frequency of these episodes.

Approved Patient Groups

This extended-release version of the medication is specifically indicated for use in the following groups:

• Adults with epilepsy.
• Children and adolescents who are at least 12 years of age.

While other forms of this medication may be used for different types of seizures or in younger children, the XR (extended-release) formulation is specifically approved for partial-onset seizures in patients 12 and older.

Usage in Epilepsy Management

Keppra XR is often used as an adjunctive therapy, which means it is taken in combination with other anti-seizure medications to improve overall seizure control. Because it is an extended-release tablet, the medicine is released slowly into the body over a 24-hour period, which typically allows for once-daily dosing.

Mechanism of Action

The exact way Keppra XR works to prevent seizures is not fully understood. However, research suggests that it binds to a specific protein in the brain known as synaptic vesicle protein 2A (SV2A). This protein is involved in how nerve cells release neurotransmitters, which are the chemical messengers used for communication between brain cells.

By interacting with this protein, the medication is believed to help regulate the release of these chemicals. This process helps to:

• Prevent sudden, abnormal bursts of electrical activity in the brain.
• Reduce the likelihood of a seizure occurring.
• Stabilize nerve cell signals.

Unlike many other anti-seizure medications, Kevetiracetam does not appear to work directly on the most common inhibitory or excitatory neurotransmitter systems in the brain.

Extended-Release Delivery

The "XR" in Keppra XR stands for extended-release. This means the tablet is specially formulated to release the active ingredient, levetiracetam, slowly into the bloodstream over a 24-hour period. This slow-release mechanism helps maintain a consistent level of the drug in the body, which provides steady protection against seizures throughout the day and allows for once-daily dosing.

Common Side Effects

Many people using Keppra XR experience mild side effects as their body adjusts to the medication. These may include:

• Drowsiness or extreme tiredness
• Dizziness
• Weakness
• Headache
• Nasal congestion or sore throat
• Irritability or nervousness
• Loss of appetite

Serious Side Effects

Some side effects can be serious and require immediate medical attention. Contact a healthcare provider right away if you experience:

• Mood and behavior changes: This includes increased aggression, agitation, anxiety, panic attacks, depression, or thoughts of self-harm or suicide.
• Severe skin reactions: Symptoms may include a rash, blisters, fever, or peeling skin. This includes rare but life-threatening conditions like Stevens-Johnson syndrome or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
• Coordination issues: Difficulty walking, loss of balance, or unusual clumsiness.
• Psychotic symptoms: Hallucinations or losing touch with reality.
• Signs of infection: Persistent fever, swollen glands, or a sore throat that does not go away.
• Extreme sleepiness: Drowsiness so severe that it interferes with daily activities.

Psychiatric and Behavioral Changes

Keppra XR may cause significant behavioral changes. These can include irritability, agitation, aggression, anxiety, apathy, and depression. In some cases, patients may experience psychotic symptoms such as hallucinations or paranoia.

Suicidal Thoughts and Behavior

Like other antiepileptic drugs, Keppra XR may increase the risk of suicidal thoughts or behavior. Monitoring for any new or worsening depression, mood changes, or suicidal ideation is important during treatment.

Serious Skin Reactions

Rare but life-threatening skin reactions have been reported, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN). These conditions require immediate medical attention and may start as a rash, fever, or swollen lymph nodes.

Central Nervous System Effects

This medication can cause extreme sleepiness (somnolence), fatigue, and coordination problems. Patients may experience dizziness or difficulty walking, which can increase the risk of falls or accidents.

Withdrawal Seizures

Stopping Keppra XR abruptly can lead to an increase in seizure frequency or the development of prolonged, life-threatening seizures (status epilepticus). If the medication needs to be discontinued, it is typically done gradually under medical supervision.

Blood and Kidney Considerations

• Blood Counts: Minor decreases in red blood cell counts, white blood cell counts, and certain infection-fighting cells (neutrophils) have been observed.
• Kidney Impairment: Because the drug is cleared by the kidneys, dosage adjustments may be necessary for individuals with decreased kidney function.

Pregnancy

If you are pregnant or planning to become pregnant, it is important to discuss the risks and benefits of Keppra XR with your healthcare provider. This medication should be used during pregnancy only if clearly needed. Because seizure control is vital for the health of both the pregnant person and the fetus, you should not start or stop taking this medication without medical supervision.

During pregnancy, physiological changes in the body may affect the concentration of levetiracetam in the blood. Healthcare providers may monitor these levels and adjust the dosage as necessary to ensure the medication remains effective.

There is a North American Antiepileptic Drug (NAAED) Pregnancy Registry that monitors outcomes in individuals who take seizure medications while pregnant. Healthcare providers often encourage patients to enroll in this registry to help improve the understanding of how these drugs affect pregnancy.

Breastfeeding

Levetiracetam, the active ingredient in Keppra XR, is excreted in human breast milk. Because of the potential for side effects in a nursing infant, a decision must be made whether to stop breastfeeding or stop the medication, depending on how essential the drug is to the mother's health.

Consult with a healthcare professional to discuss the risks and benefits of breastfeeding while using Keppra XR to determine the safest approach for you and your baby.

Dosage Forms

Keppra XR is provided in the following form:

• Extended-release oral tablets: These are film-coated tablets designed to release the medication slowly into the system over time.

This extended-release formulation is distinct from immediate-release versions of the medication, which may be available as standard tablets, oral solutions, or injections. Keppra XR tablets are intended to be swallowed whole and should not be crushed or chewed, as this would interfere with the controlled-release mechanism.

FDA Approval and Indications

Keppra XR (levetiracetam extended-release) is approved by the U.S. Food and Drug Administration (FDA) as adjunctive therapy for the treatment of partial-onset seizures. It is indicated for use in patients with epilepsy who are at least 12 years of age.

Major Safety Communications

In December 2023, the FDA issued a safety communication warning that levetiracetam products, including Keppra XR, can cause a rare but serious immune system reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). This condition may begin as a rash but can quickly progress to affect internal organs and may be life-threatening.

As a result of these findings, the FDA required the manufacturer to add new warnings regarding DRESS to the prescribing information and the patient Medication Guide. This safety concern was identified through the FDA Adverse Event Reporting System (FAERS).

Regulatory Status and Monitoring

Keppra XR is a prescription-only medication. While it does not have a boxed warning, the FDA requires a Medication Guide to be dispensed with every prescription. This guide includes standard class-wide warnings for antiepileptic drugs, such as the risk of suicidal thoughts or behaviors. The FDA continues to monitor the safety profile of levetiracetam through post-marketing surveillance.

Risks of Sudden Discontinuation

Stopping Keppra XR suddenly can cause serious medical issues. It is important to continue taking the medication as prescribed, even if you feel fine or believe you no longer need it. Abruptly ending treatment can lead to the following complications:

• Increased Seizures: Abruptly stopping the medication may cause seizures to return or occur more frequently than they did before starting treatment.
• Status Epilepticus: In some cases, sudden withdrawal can lead to status epilepticus, a life-threatening condition where seizures do not stop or occur so frequently that the person does not regain consciousness between them.

Gradual Dose Reduction

If treatment with Keppra XR needs to be discontinued, healthcare providers typically recommend a gradual reduction in dosage rather than stopping all at once. This tapering process helps the brain adjust and minimizes the risk of increased seizure activity. Always follow the specific tapering schedule provided by your doctor and do not change your dose without medical supervision.