Levetiracetam (Page 3 of 8)

5.7 Withdrawal Seizures

As with most antiepileptic drugs, levetiracetam extended-release tablets should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered.

5.8 Hematologic Abnormalities

Levetiracetam extended-release tablets can cause hematologic abnormalities. Hematologic abnormalities occurred in clinical trials and included decreases in white blood cell (WBC), neutrophil, and red blood cell (RBC) counts; decreases in hemoglobin and hematocrit; and increases in eosinophil counts. Cases of agranulocytosis, pancytopenia, and thrombocytopenia have also been reported in the postmarketing setting. A complete blood count is recommended in patients experiencing significant weakness, pyrexia, recurrent infections, or coagulation disorders.
In controlled trials of immediate-release levetiracetam tablets in patients experiencing partial-onset seizures, minor, but statistically significant, decreases compared to placebo in total mean RBC count (0.03 x 106 /mm3), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%), were seen in immediate-release levetiracetam tablets-treated patients.
A total of 3.2% of levetiracetam tablets-treated and 1.8% of placebo-treated patients had at least one possibly significant (≤2.8 x 109 /L) decreased WBC, and 2.4% of levetiracetam tablets-treated and 1.4% of placebo-treated patients had at least one possibly significant (≤1 x 109 /L) decreased neutrophil count. Of the levetiracetam tablets-treated patients with a low neutrophil count, all but one rose towards or to baseline with continued treatment. No patient was discontinued secondary to low neutrophil counts.
In pediatric patients (4 to <16 years of age), statistically significant decreases in WBC and neutrophil counts were seen in patients treated with immediate-release levetiracetam tablets, as compared to placebo. The mean decreases from baseline in the immediate-release levetiracetam tablets group were -0.4 × 109 /L and -0.3 × 109 /L, respectively, whereas there were small increases in the placebo group. A significant increase in mean relative lymphocyte counts was observed in 1.7% of patients treated with immediate-release levetiracetam tablets compared to a decrease of 4% in patients on placebo.
In the controlled pediatric trial, a possibly clinically significant abnormal low WBC value was observed in 3% of patients treated with immediate-release levetiracetam tablets, compared to no patients on placebo. However, there was no apparent difference between treatment groups with respect to neutrophil count. No patient was discontinued secondary to low WBC or neutrophil counts. In the controlled pediatric cognitive and neuropsychological safety study, two subjects (6.1%) in the placebo group and 5 subjects (8.6%) in the immediate-release levetiracetam tablets-treated group had high eosinophil count values that were possibly clinically significant (≥10% or ≥0.7X109 /L).

5.9 Seizure Control During Pregnancy

Physiological changes may gradually decrease plasma levels of levetiracetam throughout pregnancy. This decrease is more pronounced during the third trimester. It is recommended that patients be monitored carefully during pregnancy. Close monitoring should continue through the postpartum period especially if the dose was changed during pregnancy.

6 ADVERSE REACTIONS

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

6.1 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.

Levetiracetam Extended-Release Tablets

In the controlled clinical study in patients with partial-onset seizures [see Clinical Studies (14.1)] , the most common adverse reactions in patients receiving levetiracetam extended-release tablets in combination with other AEDs, for events with rates greater than placebo, were irritability and somnolence.

Table 3 lists adverse reactions that occurred in at least 5% of epilepsy patients receiving levetiracetam extended-release tablets in the placebo-controlled study and were numerically more common than in patients treated with placebo. In this study, either levetiracetam extended-release tablets or placebo was added to concurrent AED therapy.

Table 3: Adverse Reactions in the Placebo-Controlled, Adjunctive Study in Patients Experiencing Partial-Onset Seizures
Levetiracetam Extended-Release Tablets (N=77) % Placebo (N=79) %
Influenza 8 4
Somnolence 8 3
Irritability 7 0
Nasopharyngitis 7 5
Dizziness 5 3
Nausea 5 3

Discontinuation or Dose Reduction in the Levetiracetam Extended-Release Tablets Controlled Clinical Study

In the controlled clinical study, 5% of patients receiving levetiracetam extended-release tablets and 3% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions that resulted in discontinuation and that occurred more frequently in levetiracetam extended-release tablets-treated patients than in placebo-treated patients were asthenia, epilepsy, mouth ulceration, rash, and respiratory failure. Each of these adverse reactions led to discontinuation in a levetiracetam extended-release tablets-treated patient and no placebo-treated patients.

Immediate-Release Levetiracetam Tablets

Table 4 lists the adverse reactions in the controlled studies of immediate-release levetiracetam tablets in adult patients experiencing partial-onset seizures [see Clinical Studies (14.2)]. Although the pattern of adverse reactions in the levetiracetam extended-release tablets study seems somewhat different from that seen in partial-onset seizure controlled studies for immediate-release levetiracetam tablets, this is possibly due to the much smaller number of patients in this study compared to the immediate-release tablet studies. The adverse reactions for levetiracetam extended-release tablets are expected to be similar to those seen with immediate-release levetiracetam tablets.

Adults

In controlled clinical studies of immediate-release levetiracetam tablets as adjunctive therapy to other AEDs in adults with partial-onset seizures, the most common adverse reactions, for events with rates greater than placebo, were somnolence, asthenia, infection, and dizziness.

Table 4 lists adverse reactions that occurred in at least 1% of adult epilepsy patients receiving immediate-release levetiracetam tablets in placebo-controlled studies and were numerically more common than in patients treated with placebo. In these studies, either immediate-release levetiracetam tablets or placebo was added to concurrent AED therapy.

Table 4: Adverse Reactions in Pooled Placebo-Controlled, Adjunctive Studies in Adults Experiencing Partial-Onset Seizures
Immediate-Release Levetiracetam Tablets (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 0
Hostility 2 1
Paresthesia 2 1
Sinusitis 2 1

Pediatric Patients 4 Years to <16 Years

In a pooled analysis of two controlled pediatric clinical studies in children 4 to 16 years of age with partial-onset seizures [see Clinical Studies (14.3)] , the adverse reactions most frequently reported with the use of immediate-release levetiracetam tablets in combination with other AEDs, and with greater frequency than in patients on placebo, were fatigue, aggression, nasal congestion, decreased appetite, and irritability.

Table 5 lists adverse reactions that occurred in at least 2% of pediatric patients treated with immediate-release levetiracetam tablets and were more common than in pediatric patients on placebo. In these studies, either immediate-release levetiracetam tablets or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity.

Table 5: Adverse Reactions in Pooled Placebo-Controlled, Adjunctive Studies in Pediatric Patients Ages 4 to 16 Years Experiencing Partial-Onset Seizures
Immediate-Release Levetiracetam Tablets (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

In controlled pediatric clinical studies in patients 4 to 16 years of age, 7% of patients treated with immediate-release levetiracetam tablets and 9% of patients on placebo discontinued as a result of an adverse event.

In addition, the following adverse reactions were seen in other controlled studies of immediate-release levetiracetam tablets: balance disorder, disturbance in attention, eczema, hyperkinesia, memory impairment, myalgia, personality disorders, pruritus, and blurred vision.

Comparison of Gender, Age and Race

There are insufficient data for levetiracetam extended-release tablets to support a statement regarding the distribution of adverse reactions by gender, age, and race.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.