Side Effects of Keppra (levetiracetam)

Keppra (levetiracetam) is an antiseizure (antiepileptic) drug. Its mechanism of action is unknown, but it inhibits the spread of seizure activity in the brain. In studies, addition of Keppra to other antiseizure drugs reduced the frequency of seizures more than placebo.

Common side effects of Keppra include

• headache,
• sleepiness,
• weakness,
• dizziness,
• infection,
• difficulty walking or moving, and
• decreased red or white blood cell counts.

Serious side effects of Keppra include

• behavioral abnormalities (hostility, irritability, mood swings, anxiety, hallucinations, delusions, nervousness, aggression, personality disorder, and depression),
• Steven-Johnson syndrome and toxic epidermal necrolysis (severe skin reactions),
• high blood pressure, and
• increased risk of suicidal thinking and behavior.

Like other antiseizure medications, Keppra should not be discontinued suddenly because of the risk of increased seizure activity.

Drug interactions of Keppra include probenecid, which reduces the elimination of Keppra by the kidneys, potentially doubling the concentration of Keppra in the body. This could lead to side effects from probenecid.

Keppra has not been adequately studied in pregnant women. Keppra is used during pregnancy only if the benefit justifies the potential risk to the fetus.

Keppra is excreted in breast milk. To avoid potential serious side effects in infants who are breastfeeding mothers should consider not breastfeeding while taking Keppra.

Common side effects associated with levetiracetam include:

• Headache
• Sleepiness
• Weakness
• Dizziness
• Infection
• Difficulty walking or moving
• A decrease in red or white blood cell counts

In some patients Keppra causes behavioral abnormalities such as:

• Hostility
• Irritability
• Mood swings
• Anxiety
• Hallucinations
• Delusions
• Nervousness
• Hostility
• Aggression
• Personality disorder
• Nervousness
• Depression
• Anxiety

Other side effects include:

• Steven-Johnson syndrome and toxic epidermal necrolysis (severe skin reactions) in children and adults
• High blood pressure

Like other antiseizure medications, levetiracetam should not be discontinued suddenly because of the risk of increased seizure activity.

Antiepileptic medications have been associated with increased risk of suicidal thinking and behavior. Anyone considering the use of antiepileptic drugs must balance this risk of suicide with the clinical need.

Patients who are started on therapy should be closely observed for

• clinical worsening,
• suicidal thoughts, or
• unusual changes in behavior.

The following adverse reactions are discussed in more details in other sections of labeling:

• Psychiatric Symptoms
• Suicidal Behavior and Ideation
• Somnolence and Fatigue
• Anaphylaxis and Angioedema
• Serious Dermatological Reactions
• Coordination Difficulties
• Hematologic Abnormalities
• Increase in Blood Pressure

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Partial Onset Seizures

Adults

In controlled clinical studies in adults with partial onset seizures, the most common adverse reactions in patients receiving Keppra in combination with other AEDs, for events with rates greater than placebo, were

• somnolence,
• asthenia,
• infection, and
• dizziness.

Of the most common adverse reactions in adults experiencing partial onset seizures, asthenia, somnolence, and dizziness occurred predominantly during the first 4 weeks of treatment with Keppra.

Table 3 lists adverse reactions that occurred in at least 1% of adult epilepsy patients receiving Keppra in placebocontrolled studies and were numerically more common than in patients treated with placebo. In these studies, either Keppra or placebo was added to concurrent AED therapy.

Table 3: Adverse Reactions in Pooled Placebo-Controlled, Add-On Studies in Adults Experiencing Partial Onset Seizures

In controlled adult clinical studies, 15% of patients receiving Keppra and 12% receiving placebo either discontinued or had a dose reduction as a result of an adverse reaction. Table 4 lists the most common (>1%) adverse reactions that resulted in discontinuation or dose reduction and that occurred more frequently in Keppra-treated patients than in placebo-treated patients.

Table 4: Adverse Reactions that Resulted in Discontinuation or Dose Reduction in Placebo-Controlled Studies in Adult Patients Experiencing Partial Onset Seizures

Pediatric Patients 4 Years To <16 Years

The adverse reaction data presented below was obtained from a pooled analysis of two controlled pediatric clinical studies in pediatric patients 4 to 16 years of age with partial onset seizures. The most common adverse reactions in pediatric patients receiving Keppra in combination with other AEDs, for events with rates greater than placebo, were

• fatigue,
• aggression,
• nasal congestion,
• decreased appetite, and
• irritability.

Table 5 lists adverse reactions from the pooled pediatric controlled studies (4 to 16 years of age) that occurred in at least 2% of pediatric Keppra-treated patients and were numerically more common than in pediatric patients treated with placebo. In these studies, either Keppra or placebo was added to concurrent AED therapy.

Table 5: Adverse Reactions in Pooled Placebo-Controlled, Add-On Studies in Pediatric Patients Ages 4 to 16 Years Experiencing Partial Onset Seizures

In the controlled pooled pediatric clinical studies in patients 4-16 years of age, 7% of patients receiving Keppra and 9% receiving placebo discontinued as a result of an adverse reaction.

Pediatric Patients 1 Month To < 4 Years

In the 7-day, controlled pediatric clinical study in children 1 month to less than 4 years of age with partial onset seizures, the most common adverse reactions in patients receiving Keppra in combination with other AEDs, for events with rates greater than placebo, were somnolence and irritability.

Because of the shorter exposure period, incidences of adverse reactions are expected to be lower than in other pediatric studies in older patients. Therefore, other controlled pediatric data, presented above, should also be considered to apply to this age group.

Table 6 lists adverse reactions that occurred in at least 5% of pediatric epilepsy patients (ages 1 month to < 4 years) treated with Keppra in the placebo-controlled study and were numerically more common than in patients treated with placebo. In this study, either Keppra or placebo was added to concurrent AED therapy.

Table 6: Adverse Reactions in a Placebo-Controlled, Add-On Study in Pediatric Patients Ages 1 Month to < 4 Years Experiencing Partial Onset Seizures

In the 7-day controlled pediatric clinical study in patients 1 month to < 4 years of age, 3% of patients receiving Keppra and 2% receiving placebo either discontinued or had a dose reduction as a result of an adverse reaction. There was no adverse reaction that resulted in discontinuation for more than one patient.

Myoclonic Seizures

Although the pattern of adverse reactions in this study seems somewhat different from that seen in patients with partial seizures, this is likely due to the much smaller number of patients in this study compared to partial seizure studies. The adverse reaction pattern for patients with JME is expected to be essentially the same as for patients with partial seizures.

In the controlled clinical study in patients 12 years of age and older with myoclonic seizures, the most common adverse reactions in patients receiving Keppra in combination with other AEDs, for events with rates greater than placebo, were somnolence, neck pain, and pharyngitis.

Table 7 lists adverse reactions that occurred in at least 5% of juvenile myoclonic epilepsy patients experiencing myoclonic seizures treated with Keppra and were numerically more common than in patients treated with placebo. In this study, either Keppra or placebo was added to concurrent AED therapy.

Table 7: Adverse Reactions in a Placebo-Controlled, Add-On Study in Patients 12 Years of Age and Older with Myoclonic Seizures

In the placebo-controlled study, 8% of patients receiving Keppra and 2% receiving placebo either discontinued or had a dose reduction as a result of an adverse reaction. The adverse reactions that led to discontinuation or dose reduction and that occurred more frequently in Keppra-treated patients than in placebo-treated patients are presented in Table 8.

Table 8: Adverse Reactions that Resulted in Discontinuation or Dose Reduction in a Placebo-Controlled Study in Patients with Juvenile Myoclonic Epilepsy

Primary Generalized Tonic-Clonic Seizures

Although the pattern of adverse reactions in this study seems somewhat different from that seen in patients with partial seizures, this is likely due to the much smaller number of patients in this study compared to partial seizure studies. The adverse reaction pattern for patients with primary generalized tonic-clonic (PGTC) seizures is expected to be essentially the same as for patients with partial seizures.

In the controlled clinical study that included patients 4 years of age and older with PGTC seizures, the most common adverse reaction in patients receiving Keppra in combination with other AEDs, for events with rates greater than placebo, was nasopharyngitis.

Table 9 lists adverse reactions that occurred in at least 5% of idiopathic generalized epilepsy patients experiencing PGTC seizures treated with Keppra and were numerically more common than in patients treated with placebo. In this study, either Keppra or placebo was added to concurrent AED therapy.

Table 9: Adverse Reactions in a Placebo-Controlled, Add-On Study in Patients 4 Years of Age and Older with PGTC Seizures

In the placebo-controlled study, 5% of patients receiving Keppra and 8% receiving placebo either discontinued or had a dose reduction during the treatment period as a result of an adverse reaction.

This study was too small to adequately characterize the adverse reactions that could be expected to result in discontinuation of treatment in this population. It is expected that the adverse reactions that would lead to discontinuation in this population would be similar to those resulting in discontinuation in other epilepsy trials (see tables 4 and 8).

In addition, the following adverse reactions were seen in other controlled adult studies of Keppra:

• balance disorder,
• disturbance in attention,
• eczema,
• memory impairment,
• myalgia, and
• blurred vision.

Comparison Of Gender, Age And Race

The overall adverse reaction profile of Keppra was similar between females and males. There are insufficient data to support a statement regarding the distribution of adverse reactions by age and race.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Keppra. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been reported in patients receiving marketed Keppra worldwide. The listing is alphabetized:

• abnormal liver function test,
• acute kidney injury,
• anaphylaxis,
• angioedema,
• agranulocytosis,
• choreoathetosis,
• drug reaction with eosinophilia and systemic symptoms (DRESS),
• dyskinesia,
• erythema multiforme,
• hepatic failure,
• hepatitis,
• hyponatremia,
• muscular weakness,
• pancreatitis,
• pancytopenia (with bone marrow suppression identified in some of these cases),
• panic attack,
• thrombocytopenia, and
• weight loss.

Alopecia has been reported with Keppra use; recovery was observed in majority of cases where Keppra was discontinued.

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