Levetiracetam
Generic: LEVETIRACETAM
Basic Information
Manufacturer
Dr. Reddy's Laboratories Limited
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
1f3c04d9-cccb-06a3-a0f3-f7c9228ee743
Indications & Usage
1 INDICATIONS AND USAGE Levetiracetam tablets are an antiepileptic drug indicated for adjunctive therapy in the treatment of: Partial onset seizures in patients one month of age and older with epilepsy (1.1) Myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy (1.2) Primary generalized tonic-clonic seizures in patients 6 years of age and older with idiopathic generalized epilepsy (1.3) 1.1 Partial Onset Seizures Levetiracetam tablets are indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 1 month of age and older with epilepsy.
1.2 Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy Levetiracetam tablets are indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.
1.3 Primary Generalized Tonic-Clonic Seizures Levetiracetam tablets are indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.
1.2 Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy Levetiracetam tablets are indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.
1.3 Primary Generalized Tonic-Clonic Seizures Levetiracetam tablets are indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in more details in other sections of labeling: Psychiatric Symptoms [see Warnings and Precautions (5.1) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.2) ] Somnolence and Fatigue [see Warnings and Precautions (5.3) ] Serious Dermatological Reactions [see Warnings and Precautions (5.4) ] Coordination Difficulties [see Warnings and Precautions (5.5) ] Withdrawal Seizures [see Warnings and Precautions (5.6) ] Hematologic Abnormalities [see Warnings and Precautions (5.7) ] Blood Pressure Increases [see Warnings and Precautions (5.8) ] Seizure Control During Pregnancy [see Warnings and Precautions (5.9) ] Most common adverse reactions (incidence in levetiracetam-treated patients is ≥ 5% more than in placebo-treated patients) include: Adult patients: somnolence, asthenia, infection and dizziness (6.1) Pediatric patients: fatigue, aggression, nasal congestion, decreased appetite, and irritability (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
The prescriber should be aware that the adverse reaction incidence figures in the following tables, obtained when levetiracetam was added to concurrent AED therapy, cannot be used to predict the frequency of adverse reactions in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical trials.
Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators.
An inspection of these frequencies, however, does provide the prescriber with one basis to estimate the relative contribution of drug and non-drug factors to the adverse reaction incidences in the population studied.
Partial Onset Seizures Adults In controlled clinical studies in adults with partial onset seizures, the most frequently reported adverse reactions in patients receiving levetiracetam in combination with other AEDs were somnolence, asthenia, infection and dizziness.
Of the most frequently reported adverse reactions in adults experiencing partial onset seizures, asthenia, somnolence and dizziness appeared to occur predominantly during the first 4 weeks of treatment with levetiracetam.
Table 3 lists adverse reactions that occurred in at least 1% of adult epilepsy patients treated with levetiracetam participating in placebo-controlled studies and were numerically more common than in patients treated with placebo.
In these studies, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 3: Incidence (%) Of Adverse Reactions In Placebo-Controlled, Add-On Studies In Adults Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 1% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=769) % Placebo (N=439) % Body as a Whole Asthenia 15 9 Headache 14 13 Infection 13 8 Pain 7 6 Digestive System Anorexia 3 2 Nervous System Somnolence 15 8 Dizziness 9 4 Depression 4 2 Nervousness 4 2 Ataxia 3 1 Vertigo 3 1 Amnesia 2 1 Anxiety 2 1 Hostility 2 1 Paresthesia 2 1 Emotional Lability 2 0 Respiratory System Pharyngitis 6 4 Rhinitis 4 3 Cough Increased 2 1 Sinusitis 2 1 Special Senses Diplopia 2 1 In controlled adult clinical studies, 15% of patients receiving levetiracetam and 12% receiving placebo either discontinued or had a dose reduction as a result of an adverse event.
Table 4 lists the most common (>1%) adverse reactions that resulted in discontinuation or dose reduction and that occurred more frequently in levetiracetam-treated patients than in placebo-treated patients.
Table 4: Adverse Reactions That Most Commonly Resulted In Discontinuation Or Dose Reduction That Occurred More Frequently In Levetiracetam-Treated Patients In Placebo-Controlled Studies In Adult Patients Experiencing Partial Onset Seizures Adverse Reaction Levetiracetam (N=769) % Placebo (N=439) % Dizziness 1 0 Somnolence 4 2 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 children 4 to 16 years of age with partial onset seizures.
The adverse reactions most frequently reported with the use of levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, 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 levetiracetam-treated patients and were numerically more common than in pediatric patients treated with placebo.
In these studies, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 5: Incidence (%) Of Adverse Reactions In Pooled Placebo-Controlled, Add-On Studies In Pediatric Patients Ages 4 to 16 Years Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 2% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=165) % Placebo (N=131) % Ear and Labyrinth Disorders Ear Pain 2 1 Eye Disorders Conjunctivitis 2 0 Gastrointestinal Disorders Vomiting 15 12 Abdominal Pain Upper 9 8 Diarrhea 6 5 Constipation 3 1 General Disorders and Administration Site Conditions Fatigue 11 5 Infections and Infestations Nasopharyngitis 15 12 Influenza 3 1 Gastroenteritis 2 0 Rhinitis 2 0 Injury, Poisoning and Procedural Complications Head Injury 4 0 Contusion 3 1 Fall 3 2 Joint Sprain 2 1 Metabolism and Nutrition Disorders Decreased Appetite 8 2 Anorexia 4 3 Musculoskeletal and Connective Tissue Disorders Arthralgia 2 0 Neck Pain 2 1 Nervous System Headache 19 15 Somnolence 13 9 Dizziness 7 5 Lethargy 6 2 Sedation 2 1 Psychiatric Disorders Aggression 10 5 Abnormal Behavior 7 4 Irritability 7 1 Insomnia 5 3 Agitation 4 1 Depression 3 1 Mood Altered 3 1 Affect Lability 2 1 Anxiety 2 1 Confusional State 2 0 Mood Swings 2 1 Respiratory, Thoracic and Mediastinal Disorders Cough 9 5 Nasal Congestion 9 2 Pharyngolaryngeal Pain 7 4 In the well controlled pooled pediatric clinical studies in patients 4 to 16 years of age, 7% of patients receiving levetiracetam and 9% receiving placebo discontinued as a result of an adverse event.
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 adverse reactions most frequently reported with the use of levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, were somnolence and irritability.
Because of the shorter exposure period, incidences of adverse reactions are expected to be lower then 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 levetiracetam participating in the placebo-controlled study and were numerically more common than in patients treated with placebo.
In this study, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 6: Incidence (%) Of Adverse Reactions In A Placebo-Controlled, Add-On Study In Pediatric Patients Ages 1 Month to < 4 Years Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 5% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=60) % Placebo (N=56) % Nervous System Somnolence 13 2 Psychiatric Disorders Irritability 12 0 In the 7-day controlled pediatric clinical study in patients 1 month to < 4 years of age, 3% of patients receiving levetiracetam and 2% receiving placebo either discontinued or had a dose reduction as a result of an adverse event.
There was no adverse event 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 well-controlled clinical study that included both adolescent (12 to 16 years of age) and adult patients with myoclonic seizures, the most frequently reported adverse reactions in patients using levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, 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 levetiracetam and were numerically more common than in patients treated with placebo.
In this study, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 7: Incidence (%) Of Adverse Reactions In A Placebo-Controlled, Add-On Study In Patients 12 Years Of Age And Older With Myoclonic Seizures By Body System (Adverse Reactions Occurred In At Least 5% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=60) % Placebo (N=60) % Ear and labyrinth disorders Vertigo 5 3 Infections and infestations Pharyngitis 7 0 Influenza 5 2 Musculoskeletal and connective tissue disorders Neck pain 8 2 Nervous system disorders Somnolence 12 2 Psychiatric disorders Depression 5 2 In the placebo-controlled study, 8% of patients receiving levetiracetam 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 in the well-controlled study and occurred more frequently in levetiracetam-treated patients than in placebo-treated patients are presented in Table 8.
Table 8: Adverse Reactions That Resulted In Discontinuation Or Dose Reduction That Occurred More Frequently in Levetiracetam-Treated Patients In The Placebo-Controlled Study In Patients With Juvenile Myoclonic Epilepsy Adverse Reaction Levetiracetam (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 PGTC seizures is expected to be essentially the same as for patients with partial seizures.
In the well-controlled clinical study that included patients 4 years of age and older with primary generalized tonic-clonic (PGTC) seizures, the most frequently reported adverse reaction in patients using levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, was nasopharyngitis.
Table 9 lists adverse reactions that occurred in at least 5% of idiopathic generalized epilepsy patients experiencing PGTC seizures treated with levetiracetam and were numerically more common than in patients treated with placebo.
In this study, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 9: Incidence (%) Of Adverse Reactions In A Placebo-Controlled, Add-On Study In Patients 4 Years Of Age And Older With PGTC Seizures By MedDRA System Organ Class (Adverse Reactions Occurred In At Least 5% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=79) % Placebo (N=84) % Gastrointestinal disorders Diarrhea 8 7 General disorders and administration site conditions Fatigue 10 8 Infections and infestations Nasopharyngitis 14 5 Psychiatric disorders Irritability 6 2 Mood Swings 5 1 In the placebo-controlled study, 5% of patients receiving levetiracetam 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 well-controlled adult studies of levetiracetam: balance disorder, disturbance in attention, eczema, memory impairment, myalgia, and vision blurred.
Comparison of Gender, Age and Race The overall adverse reaction profile of levetiracetam was similar between females and males.
There are insufficient data to support a statement regarding the distribution of adverse experience reports by age and race.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of levetiracetam.
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.
In addition to the adverse reactions listed above, [see Adverse Reactions (6.1) ], the following adverse events have been reported in patients receiving marketed levetiracetam worldwide.
The listing is alphabetized: abnormal liver function test, erythema multiforme, hepatic failure, hepatitis, leukopenia, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression identified in some of these cases), thrombocytopenia, and weight loss.
Alopecia has been reported with levetiracetam use; recovery was observed in majority of cases where levetiracetam was discontinued.
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.
The prescriber should be aware that the adverse reaction incidence figures in the following tables, obtained when levetiracetam was added to concurrent AED therapy, cannot be used to predict the frequency of adverse reactions in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical trials.
Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators.
An inspection of these frequencies, however, does provide the prescriber with one basis to estimate the relative contribution of drug and non-drug factors to the adverse reaction incidences in the population studied.
Partial Onset Seizures Adults In controlled clinical studies in adults with partial onset seizures, the most frequently reported adverse reactions in patients receiving levetiracetam in combination with other AEDs were somnolence, asthenia, infection and dizziness.
Of the most frequently reported adverse reactions in adults experiencing partial onset seizures, asthenia, somnolence and dizziness appeared to occur predominantly during the first 4 weeks of treatment with levetiracetam.
Table 3 lists adverse reactions that occurred in at least 1% of adult epilepsy patients treated with levetiracetam participating in placebo-controlled studies and were numerically more common than in patients treated with placebo.
In these studies, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 3: Incidence (%) Of Adverse Reactions In Placebo-Controlled, Add-On Studies In Adults Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 1% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=769) % Placebo (N=439) % Body as a Whole Asthenia 15 9 Headache 14 13 Infection 13 8 Pain 7 6 Digestive System Anorexia 3 2 Nervous System Somnolence 15 8 Dizziness 9 4 Depression 4 2 Nervousness 4 2 Ataxia 3 1 Vertigo 3 1 Amnesia 2 1 Anxiety 2 1 Hostility 2 1 Paresthesia 2 1 Emotional Lability 2 0 Respiratory System Pharyngitis 6 4 Rhinitis 4 3 Cough Increased 2 1 Sinusitis 2 1 Special Senses Diplopia 2 1 In controlled adult clinical studies, 15% of patients receiving levetiracetam and 12% receiving placebo either discontinued or had a dose reduction as a result of an adverse event.
Table 4 lists the most common (>1%) adverse reactions that resulted in discontinuation or dose reduction and that occurred more frequently in levetiracetam-treated patients than in placebo-treated patients.
Table 4: Adverse Reactions That Most Commonly Resulted In Discontinuation Or Dose Reduction That Occurred More Frequently In Levetiracetam-Treated Patients In Placebo-Controlled Studies In Adult Patients Experiencing Partial Onset Seizures Adverse Reaction Levetiracetam (N=769) % Placebo (N=439) % Dizziness 1 0 Somnolence 4 2 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 children 4 to 16 years of age with partial onset seizures.
The adverse reactions most frequently reported with the use of levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, 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 levetiracetam-treated patients and were numerically more common than in pediatric patients treated with placebo.
In these studies, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 5: Incidence (%) Of Adverse Reactions In Pooled Placebo-Controlled, Add-On Studies In Pediatric Patients Ages 4 to 16 Years Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 2% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=165) % Placebo (N=131) % Ear and Labyrinth Disorders Ear Pain 2 1 Eye Disorders Conjunctivitis 2 0 Gastrointestinal Disorders Vomiting 15 12 Abdominal Pain Upper 9 8 Diarrhea 6 5 Constipation 3 1 General Disorders and Administration Site Conditions Fatigue 11 5 Infections and Infestations Nasopharyngitis 15 12 Influenza 3 1 Gastroenteritis 2 0 Rhinitis 2 0 Injury, Poisoning and Procedural Complications Head Injury 4 0 Contusion 3 1 Fall 3 2 Joint Sprain 2 1 Metabolism and Nutrition Disorders Decreased Appetite 8 2 Anorexia 4 3 Musculoskeletal and Connective Tissue Disorders Arthralgia 2 0 Neck Pain 2 1 Nervous System Headache 19 15 Somnolence 13 9 Dizziness 7 5 Lethargy 6 2 Sedation 2 1 Psychiatric Disorders Aggression 10 5 Abnormal Behavior 7 4 Irritability 7 1 Insomnia 5 3 Agitation 4 1 Depression 3 1 Mood Altered 3 1 Affect Lability 2 1 Anxiety 2 1 Confusional State 2 0 Mood Swings 2 1 Respiratory, Thoracic and Mediastinal Disorders Cough 9 5 Nasal Congestion 9 2 Pharyngolaryngeal Pain 7 4 In the well controlled pooled pediatric clinical studies in patients 4 to 16 years of age, 7% of patients receiving levetiracetam and 9% receiving placebo discontinued as a result of an adverse event.
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 adverse reactions most frequently reported with the use of levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, were somnolence and irritability.
Because of the shorter exposure period, incidences of adverse reactions are expected to be lower then 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 levetiracetam participating in the placebo-controlled study and were numerically more common than in patients treated with placebo.
In this study, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 6: Incidence (%) Of Adverse Reactions In A Placebo-Controlled, Add-On Study In Pediatric Patients Ages 1 Month to < 4 Years Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 5% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=60) % Placebo (N=56) % Nervous System Somnolence 13 2 Psychiatric Disorders Irritability 12 0 In the 7-day controlled pediatric clinical study in patients 1 month to < 4 years of age, 3% of patients receiving levetiracetam and 2% receiving placebo either discontinued or had a dose reduction as a result of an adverse event.
There was no adverse event 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 well-controlled clinical study that included both adolescent (12 to 16 years of age) and adult patients with myoclonic seizures, the most frequently reported adverse reactions in patients using levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, 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 levetiracetam and were numerically more common than in patients treated with placebo.
In this study, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 7: Incidence (%) Of Adverse Reactions In A Placebo-Controlled, Add-On Study In Patients 12 Years Of Age And Older With Myoclonic Seizures By Body System (Adverse Reactions Occurred In At Least 5% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=60) % Placebo (N=60) % Ear and labyrinth disorders Vertigo 5 3 Infections and infestations Pharyngitis 7 0 Influenza 5 2 Musculoskeletal and connective tissue disorders Neck pain 8 2 Nervous system disorders Somnolence 12 2 Psychiatric disorders Depression 5 2 In the placebo-controlled study, 8% of patients receiving levetiracetam 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 in the well-controlled study and occurred more frequently in levetiracetam-treated patients than in placebo-treated patients are presented in Table 8.
Table 8: Adverse Reactions That Resulted In Discontinuation Or Dose Reduction That Occurred More Frequently in Levetiracetam-Treated Patients In The Placebo-Controlled Study In Patients With Juvenile Myoclonic Epilepsy Adverse Reaction Levetiracetam (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 PGTC seizures is expected to be essentially the same as for patients with partial seizures.
In the well-controlled clinical study that included patients 4 years of age and older with primary generalized tonic-clonic (PGTC) seizures, the most frequently reported adverse reaction in patients using levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, was nasopharyngitis.
Table 9 lists adverse reactions that occurred in at least 5% of idiopathic generalized epilepsy patients experiencing PGTC seizures treated with levetiracetam and were numerically more common than in patients treated with placebo.
In this study, either levetiracetam or placebo was added to concurrent AED therapy.
Adverse reactions were usually mild to moderate in intensity.
Table 9: Incidence (%) Of Adverse Reactions In A Placebo-Controlled, Add-On Study In Patients 4 Years Of Age And Older With PGTC Seizures By MedDRA System Organ Class (Adverse Reactions Occurred In At Least 5% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients) Body System/ Adverse Reaction Levetiracetam (N=79) % Placebo (N=84) % Gastrointestinal disorders Diarrhea 8 7 General disorders and administration site conditions Fatigue 10 8 Infections and infestations Nasopharyngitis 14 5 Psychiatric disorders Irritability 6 2 Mood Swings 5 1 In the placebo-controlled study, 5% of patients receiving levetiracetam 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 well-controlled adult studies of levetiracetam: balance disorder, disturbance in attention, eczema, memory impairment, myalgia, and vision blurred.
Comparison of Gender, Age and Race The overall adverse reaction profile of levetiracetam was similar between females and males.
There are insufficient data to support a statement regarding the distribution of adverse experience reports by age and race.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of levetiracetam.
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.
In addition to the adverse reactions listed above, [see Adverse Reactions (6.1) ], the following adverse events have been reported in patients receiving marketed levetiracetam worldwide.
The listing is alphabetized: abnormal liver function test, erythema multiforme, hepatic failure, hepatitis, leukopenia, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression identified in some of these cases), thrombocytopenia, and weight loss.
Alopecia has been reported with levetiracetam use; recovery was observed in majority of cases where levetiracetam was discontinued.