KEPPRA SIDE EFFECTS
- Generic Name: levetiracetam
- Brand Name: Keppra
- Drug Class: Ligands
SIDE EFFECTS
The following adverse reactions are discussed in more details in other sections of labeling:
- Behavioral Abnormalities and Psychotic Symptoms
- 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.
The adverse reactions that result from KEPPRA injection use include all of those reported for KEPPRA tablets and oral solution. Equivalent doses of intravenous (IV) levetiracetam and oral levetiracetam result in equivalent Cmax, Cmin, and total systemic exposure to levetiracetam when the IV levetiracetam is administered as a 15-minute infusion.
Partial-Onset Seizures
Adults
In controlled clinical studies using KEPPRA tablets in adults with partial-onset seizures, the most common adverse reactions in adult 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 1 lists adverse reactions that occurred in at least 1% of adult epilepsy patients receiving KEPPRA tablets in placebo-controlled 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 1: Adverse Reactions* in Pooled Placebo-Controlled, Adjunctive Studies in Adults Experiencing Partial-Onset Seizures
KEPPRA (N=769) % |
Placebo (N=439) % |
|
Asthenia | 15 | 9 |
Somnolence | 15 | 8 |
Headache | 14 | 13 |
Infection | 13 | 8 |
Dizziness | 9 | 4 |
Pain | 7 | 6 |
Pharyngitis | 6 | 4 |
Depression | 4 | 2 |
Nervousness | 4 | 2 |
Rhinitis | 4 | 3 |
Anorexia | 3 | 2 |
Ataxia | 3 | 1 |
Vertigo | 3 | 1 |
Amnesia | 2 | 1 |
Anxiety | 2 | 1 |
Cough Increased | 2 | 1 |
Diplopia | 2 | 1 |
Emotional Lability | 2 | |
Hostility | 2 | 1 |
Paresthesia | 2 | 1 |
Sinusitis | 2 | 1 |
* Adverse reactions occurred in at least 1% of KEPPRA-treated patients and occurred more frequently than placebo-treated patients |
In controlled adult clinical studies using KEPPRA tablets, 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 2: Adverse Reactions that Resulted in Discontinuation or Dose Reduction in Pooled Placebo-Controlled Studies in Adults Experiencing Partial-Onset Seizures
Adverse Reaction | KEPPRA (N=769)% |
Placebo (N=439)% |
Somnolence | 4 | 2 |
Dizziness | 1 | 0 |
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 using an oral formulation 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 3 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 3: Adverse Reactions* in Pooled Placebo-Controlled, Adjunctive Studies in Pediatric Patients Ages 4 to 16 Years Experiencing Partial-Onset Seizures
KEPPRA (N=165) % |
Placebo (N=131) % |
|
Headache | 19 | 15 |
Nasopharyngitis | 15 | 12 |
Vomiting | 15 | 12 |
Somnolence | 13 | 9 |
Fatigue | 11 | 5 |
Aggression | 10 | 5 |
Upper Abdominal Pain | 9 | 8 |
Cough | 9 | 5 |
Nasal Congestion | 9 | 2 |
Decreased Appetite | 8 | 2 |
Abnormal Behavior | 7 | 4 |
Dizziness | 7 | 5 |
Irritability | 7 | 1 |
Pharyngolaryngeal Pain | 7 | 4 |
Diarrhea | 6 | 2 |
Lethargy | 6 | 5 |
Insomnia | 5 | 3 |
Agitation | 4 | 1 |
Anorexia | 4 | 3 |
Head Injury | 4 | 0 |
Constipation | 3 | 1 |
Contusion | 3 | 1 |
Depression | 3 | 1 |
Fall | 3 | 2 |
Influenza | 3 | 1 |
Mood Altered | 3 | 1 |
Affect Lability | 2 | 1 |
Anxiety | 2 | 1 |
Arthralgia | 2 | 0 |
Confusional State | 2 | 0 |
Conjunctivitis | 2 | 0 |
Ear Pain | 2 | 1 |
Gastroenteritis | 2 | 0 |
Joint Sprain | 2 | 1 |
Mood Swings | 2 | 1 |
Neck Pain | 2 | 1 |
Rhinitis | 2 | 0 |
Sedation | 2 | 1 |
* Adverse reactions occurred in at least 2% of pediatric KEPPRA-treated patients and occurred more frequently than placebo-treated patients |
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 using an oral formulation of KEPPRA 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 4 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 4: Adverse Reactions* in a Placebo-Controlled, Adjunctive Study in Pediatric Patients Ages 1 Month to < 4 Years Experiencing Partial-Onset Seizures
KEPPRA (N=60) % |
Placebo (N=56) % |
|
Somnolence | 13 | 2 |
Irritability | 12 | 0 |
* Adverse reactions occurred in at least 5% of KEPPRA-treated patients and occurred more frequently than placebo-treated patients |
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-onset 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 using KEPPRA tablets in patients 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 5 lists adverse reactions that occurred in at least 5% of juvenile myoclonic epilepsy patients experiencing myoclonic seizures treated with KEPPRA tablets 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 5: Adverse Reactions* in a Placebo-Controlled, Adjunctive Study in Patients 12 Years of Age and Older with Myoclonic Seizures
KEPPRA (N=60) % |
Placebo (N=60) % |
|
Somnolence | 12 | 2 |
Neck pain | 8 | 2 |
Pharyngitis | 7 | 0 |
Depression | 5 | 2 |
Influenza | 5 | 2 |
Vertigo | 5 | 3 |
* Adverse reactions occurred in at least 5% of KEPPRA-treated patients and occurred more frequently than placebo-treated patients |
In the placebo-controlled study using KEPPRA tablets in patients with JME, 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 6.
Table 6: Adverse Reactions that Resulted in Discontinuation or Dose Reduction in Patients with Juvenile Myoclonic Epilepsy
Adverse Reaction | KEPPRA (N=60) % |
Placebo (N=60) % |
Anxiety | 3 | 2 |
Depressed mood | 2 | 0 |
Depression | 2 | 0 |
Diplopia | 2 | 0 |
Hypersomnia | 2 | 0 |
Insomnia | 2 | 0 |
Irritability | 2 | 0 |
Nervousness | 2 | 0 |
Somnolence | 2 | 0 |
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 oral formulation in combination with other AEDs, for events with rates greater than placebo was nasopharyngitis.
Table 7 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 7: Adverse Reactions* in a Placebo-Controlled, Adjunctive Study in Patients 4 Years of Age and Older with PGTC Seizures
KEPPRA (N=79) % |
Placebo (N=84) % |
|
Nasopharyngitis | 14 | 5 |
Fatigue | 10 | 8 |
Diarrhea | 8 | 7 |
Irritability | 6 | 2 |
Mood swings | 5 | 1 |
* Adverse reactions occurred in at least 5% of KEPPRA-treated patients and occurred more frequently than placebo-treated patients |
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 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, weight loss, and worsening of seizures. Alopecia has been reported with KEPPRA use; recovery was observed in majority of cases where KEPPRA was discontinued.
SRC: NLM .