Levetiracetam (Levetiracetam) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

The prescriber should be aware that the adverse event incidence figures in the following tables, obtained when Levetiracetam was added to concurrent AED therapy, cannot be used to predict the frequency of adverse experiences in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. 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 event incidences in the population studied.

Partial Onset Seizures

In well-controlled clinical studies in adults with partial onset seizures, the most frequently reported adverse events associated with the use of Levetiracetam in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, were somnolence, asthenia, infection and dizziness. In the well-controlled pediatric clinical study in children 4 to 16 years of age with partial onset seizures, the adverse events 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, accidental injury, hostility, nervousness, and asthenia.

Table 5 lists treatment-emergent adverse events 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. Table 6 lists treatment-emergent adverse events that occurred in at least 2% of pediatric epilepsy patients (ages 4 to 16 years) treated with Levetiracetam participating in the placebo-controlled study 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 events were usually mild to moderate in intensity.

Table 5: Incidence (%) Of Treatment-Emergent Adverse Events In Placebo-Controlled, Add-On Studies In Adults Experiencing Partial Onset Seizures By Body System (Adverse Events Occurred In At Least 1% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)

Body System/         Adverse Event	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

Other events reported by at least 1% of adult levetiracetam-treated patients but as or more frequent in the placebo group were the following: abdominal pain, accidental injury, amblyopia, arthralgia, back pain, bronchitis, chest pain, confusion, constipation, convulsion, diarrhea, drug level increased, dyspepsia, ecchymosis, fever, flu syndrome, fungal infection, gastroenteritis, gingivitis, grand mal convulsion, insomnia, nausea, otitis media, rash, thinking abnormal, tremor, urinary tract infection, vomiting and weight gain.

Table 6: Incidence (%) Of Treatment-Emergent Adverse Events In A Placebo-Controlled, Add-On Study In Pediatric Patients Ages 4 to 16 Years Experiencing Partial Onset Seizures By Body System (Adverse Events Occurred In At Least 2% Of Levetiracetam-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)

Body System/         Adverse Event	Levetiracetam (N=101) %	Placebo (N=97) %
Body as a Whole
Accidental Injury	17	10
Asthenia	9	3
Pain	6	3
Flu Syndrome	3	2
Face Edema	2	1
Neck Pain	2	1
Viral Infection	2	1
Digestive System
Vomiting	15	13
Anorexia	13	8
Diarrhea	8	7
Gastroenteritis	4	2
Constipation	3	1
Hemic and Lymphatic System
Ecchymosis	4	1
Metabolic and Nutritional
Dehydration	2	1
Nervous System
Somnolence	23	11
Hostility	12	6
Nervousness	10	2
Personality Disorder	8	7
Dizziness	7	2
Emotional Lability	6	4
Agitation	6	1
Depression	3	1
Vertigo	3	1
Reflexes Increased	2	1
Confusion	2	0
Respiratory System
Rhinitis	13	8
Cough Increased	11	7
Pharyngitis	10	8
Asthma	2	1
Skin and Appendages
Pruritus	2	0
Skin Discoloration	2	0
Vesiculobullous Rash	2	0
Special Senses
Conjunctivitis	3	2
Amblyopia	2	0
Ear Pain	2	0
Urogenital System
Albuminuria	4	0
Urine Abnormality	2	1

Other events occurring in at least 2% of pediatric levetiracetam-treated patients but as or more frequent in the placebo group were the following: abdominal pain, allergic reaction, ataxia, convulsion, epistaxis, fever, headache, hyperkinesia, infection, insomnia, nausea, otitis media, rash, sinusitis, status epilepticus (not otherwise specified), thinking abnormal, tremor, and urinary incontinence.

Time Course Of Onset Of Adverse Events For Partial Onset Seizures

Of the most frequently reported adverse events in adults experiencing partial onset seizures, asthenia, somnolence and dizziness appeared to occur predominantly during the first 4 weeks of treatment with Levetiracetam.

Discontinuation Or Dose Reduction In Well-Controlled Clinical Studies

Partial Onset Seizures

In well-controlled adult clinical studies, 15.0% of patients receiving Levetiracetam and 11.6% receiving placebo either discontinued or had a dose reduction as a result of an adverse event. Table 7 lists the most common (>1%) adverse events that resulted in or dose reduction.

Table 7: Adverse Events That Most Commonly Resulted In Discontinuation Or Dose Reduction In Placebo-Controlled Studies In Adult Patients Experiencing Partial Onset Seizures

	Number (%)
	Levetiracetam (N=769)	Placebo (N=439)
Asthenia	10 (1.3%)	3 (0.7%)
Convulsion	23 (3.0%)	15 (3.4%)
Dizziness	11 (1.4%)	0
Rash	0	5 (1.1%)
Somnolence	34 (4.4%)	7 (1.6%)

In the well-controlled pediatric clinical study, 16.8% of patients receiving Levetiracetam and 20.6% receiving placebo either discontinued or had a dose reduction as a result of an adverse event. The adverse events most commonly associated (≥3% in patients receiving Levetiracetam) with discontinuation or dose reduction in the well-controlled study are presented in Table 8.

Table 8: Adverse Events Most Commonly Associated With Discontinuation Or Dose Reduction In The Placebo-Controlled Study In Pediatric Patients Ages 4 to 16 Years Experiencing Partial Onset Seizures

	Number (%)
	Levetiracetam (N=101)	Placebo (N=97)
Asthenia	3 (3.0%)	0
Hostility	7 (6.9%)	2 (2.1%)
Somnolence	3 (3.0%)	3 (3.1%)

Comparison Of Gender, Age And Race

The overall adverse experience 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.

Postmarketing Experience

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

In addition to the adverse experiences listed above, the following have been reported in patients receiving marketed Levetiracetam worldwide. The listing is alphabetized: abnormal liver function test, 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. There have been reports of suicidal behavior (including completed suicide) with marketed Levetiracetam. These adverse experiences have not been listed above, and data are insufficient to support an estimate of their incidence or to establish causation.

REPORTS OF SUSPECTED LEVETIRACETAM SIDE EFFECTS / ADVERSE REACTIONS

Possible Levetiracetam side effects / adverse reactions in 30 year old male

Reported by a physician from Denmark on 2011-10-03

Patient: 30 year old male

Reactions: White Blood Cell Count Decreased, Neutrophil Count Decreased, Constipation

Suspect drug(s):
Levetiracetam
    Dosage: 1000 mg;qd
    Indication: Epilepsy

Valproic Acid
    Dosage: 2000 mg;qd

Clozaril
    Dosage: 400 mg;qd
    Indication: Schizophrenia
    Start date: 2004-04-28

Other drugs received by patient: Lactulose; Lansoprazole

Possible Levetiracetam side effects / adverse reactions in 61 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-05

Patient: 61 year old female

Reactions: Myoclonus, Drug Ineffective, Dyskinesia

Suspect drug(s):
Carbidopa and Levodopa
    Indication: Parkinson's Disease

Ropinirole
    Indication: Parkinson's Disease

Levetiracetam
    Indication: Dyskinesia

Trihexyphenidyl HCL
    Indication: Parkinson's Disease

Possible Levetiracetam side effects / adverse reactions in 30 year old male

Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2011-10-05

Patient: 30 year old male

Reactions: White Blood Cell Count Decreased, Constipation, Neutrophil Count Decreased, Abdominal Pain Upper

Suspect drug(s):
Levetiracetam
    Dosage: daily dose: 1000 milligrams
    Administration route: Oral
    Indication: Epilepsy

Valproate Sodium
    Dosage: daily dose: 2000 milligrams
    Administration route: Oral
    Indication: Epilepsy

Clozapine
    Dosage: daily dose: 400 milligrams; daily
    Administration route: Oral

Clozapine
    Dosage: daily dose: 400 milligrams; daily
    Administration route: Oral
    Indication: Schizophrenia
    Start date: 2004-04-28

Other drugs received by patient: Lansoprazole