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Keppra (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 KEPPRA 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 KEPPRA 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 KEPPRA in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, were somnolence, accidental injury, hostility, nervousness, and asthenia.

Table 8 lists treatment-emergent adverse events that occurred in at least 1% of adult epilepsy patients treated with KEPPRA participating in placebo-controlled studies and were numerically more common than in patients treated with placebo. Table 9 lists treatment-emergent adverse events that occurred in at least 2% of pediatric epilepsy patients (ages 4-16 years) treated with KEPPRA participating in the placebo-controlled study 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. Adverse events were usually mild to moderate in intensity.

Table 8: 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 KEPPRA-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)
Body System/
        Adverse Event
KEPPRA
(N=769)
%
Placebo
(N=439)
%
Body as a Whole
      Asthenia159
      Headache 1413
      Infection138
      Pain76
Digestive System
      Anorexia32
Nervous System
      Somnolence158
      Dizziness94
      Depression42
      Nervousness42
      Ataxia31
      Vertigo31
      Amnesia21
      Anxiety21
      Hostility21
      Paresthesia21
      Emotional Lability20
Respiratory System
      Pharyngitis64
      Rhinitis43
      Cough Increased21
      Sinusitis21
Special Senses
      Diplopia21

Other events reported by at least 1% of adult KEPPRA-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 9: Incidence (%) Of Treatment-Emergent Adverse Events In A Placebo-Controlled, Add-On Study In Pediatric Patients Ages 4-16 Years Experiencing Partial Onset Seizures By Body System (Adverse Events Occurred In At Least 2% Of KEPPRA-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)
Body System/
        Adverse Event
KEPPRA
(N=101)
%
Placebo
(N=97)
%
Body as a Whole
      Accidental Injury1710
      Asthenia93
      Pain63
      Flu Syndrome32
      Face Edema21
      Neck Pain21
      Viral Infection21
Digestive System
      Vomiting1513
      Anorexia138
      Diarrhea87
      Gastroenteritis42
      Constipation31
Hemic and Lymphatic System
      Ecchymosis41
Metabolic and Nutritional
      Dehydration21
Nervous System
      Somnolence2311
      Hostility126
      Nervousness102
      Personality Disorder87
      Dizziness72
      Emotional Lability64
      Agitation61
      Depression31
      Vertigo31
      Reflexes Increased21
      Confusion20
Respiratory System
      Rhinitis138
      Cough Increased117
      Pharyngitis108
      Asthma21
Skin and Appendages
      Pruritus20
      Skin Discoloration20
      Vesiculobullous Rash20
Special Senses
      Conjunctivitis32
      Amblyopia20
      Ear Pain20
Urogenital System
      Albuminuria40
      Urine Abnormality21

Other events occurring in at least 2% of pediatric KEPPRA-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.

Myoclonic Seizures

Although the pattern of adverse events 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 event 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 events associated with the use of KEPPRA in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, were somnolence, neck pain, and pharyngitis.

Table 10 lists treatment-emergent adverse events 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. Adverse events were usually mild to moderate in intensity.

Table 10: Incidence (%) Of Treatment-Emergent Adverse Events In A Placebo-Controlled, Add-On Study In Patients 12 Years Of Age And Older With Myoclonic Seizures By Body System (Adverse Events Occurred In At Least 5% Of KEPPRA-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)
Body System /
    MedDRA preferred term
KEPPRA
(N=60)
%
Placebo
(N=60)
%
Ear and labyrinth disorders
    Vertigo53
Infections and infestations
    Pharyngitis7 0
    Influenza52
Musculoskeletal and connective tissue disorders
    Neck pain82
Nervous system disorders
    Somnolence122
Psychiatric disorders
    Depression52

Other events occurring in at least 5% of KEPPRA-treated patients with myoclonic seizures but as or more frequent in the placebo group were the following: fatigue and headache.

Primary Generalized Tonic-Clonic Seizures

Although the pattern of adverse events 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 event 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 event associated with the use of KEPPRA in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, was nasopharyngitis.

Table 11 lists treatment-emergent adverse events 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. Adverse events were usually mild to moderate in intensity.

Table 11: Incidence (%) Of Treatment-Emergent Adverse Events In A Placebo-Controlled, Add-On Study In Patients 4 Years Of Age And Older With PGTC Seizures By MedDRA System Organ Class (Adverse Events Occurred In At Least 5% Of KEPPRA-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)
MedDRA System Organ Class/
     Preferred Term
KEPPRA
(N=79)
%
Placebo
(N=84)
%
Gastrointestinal disorders
    Diarrhea87
General disorders and administration site conditions
    Fatigue108
Infections and infestations
    Nasopharyngitis145
Psychiatric disorders
    Irritability62
    Mood swings51

Other events occurring in at least 5% of KEPPRA-treated patients with PGTC seizures but as or more frequent in the placebo group were the following: dizziness, headache, influenza, and somnolence.

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 KEPPRA.

Discontinuation Or Dose Reduction In Well-Controlled Clinical Studies

Partial Onset Seizures

In well-controlled adult clinical studies, 15.0% of patients receiving KEPPRA and 11.6% receiving placebo either discontinued or had a dose reduction as a result of an adverse event. Table 12 lists the most common (>1%) adverse events that resulted in discontinuation or dose reduction.

Table 12: Adverse Events That Most Commonly Resulted In Discontinuation Or Dose Reduction In Placebo-Controlled Studies In Adult Patients Experiencing Partial Onset Seizures
Number (%)
KEPPRA
(N=769)
Placebo
(N=439)
Asthenia10 (1.3%)3 (0.7%)
Convulsion23 (3.0%)15 (3.4%)
Dizziness11 (1.4%)0
Rash05 (1.1%)
Somnolence34 (4.4%)7 (1.6%)

In the well-controlled pediatric clinical study, 16.8% of patients receiving KEPPRA 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 KEPPRA) with discontinuation or dose reduction in the well-controlled study are presented in Table 13.

Table 13: Adverse Events Most Commonly Associated With Discontinuation Or Dose Reduction In The Placebo-Controlled Study In Pediatric Patients Ages 4-16 Years Experiencing Partial Onset Seizures
Number (%)
KEPPRA
(N=101)
Placebo
(N=97)
Asthenia3 (3.0%)0
Hostility7 (6.9%)2 (2.1%)
Somnolence3 (3.0%)3 (3.1%)

Myoclonic Seizures

In the placebo-controlled study, 8.3% of patients receiving KEPPRA and 1.7% receiving placebo either discontinued or had a dose reduction as a result of an adverse event. The adverse events that led to discontinuation or dose reduction in the well-controlled study are presented in Table 14.

Table 14: Adverse Events That Resulted In Discontinuation Or Dose Reduction In The Placebo-Controlled Study In Patients With Juvenile Myoclonic Epilepsy
Body System/
   MedDRA preferred term
KEPPRA
(N=60)
n (%)
Placebo
(N=60)
n (%)
    Anxiety2 (3.3%)1 (1.7%)
    Depressed mood1 (1.7%)0
    Depression1 (1.7%)0
    Diplopia1 (1.7%)0
    Hypersomnia 1 (1.7%)0
    Insomnia1 (1.7%)0
    Irritability1 (1.7%)0
    Nervousness 1 (1.7%)0
    Somnolence1 (1.7%)0

Primary Generalized Tonic-Clonic Seizures

In the placebo-controlled study, 5.1% of patients receiving KEPPRA and 8.3% receiving placebo either discontinued or had a dose reduction during the treatment period as a result of a treatment-emergent adverse event.

This study was too small to adequately characterize the adverse events leading to discontinuation. It is expected that the adverse events that would lead to discontinuation in this population would be similar to those resulting in discontinuation in other epilepsy trials (see tables 12 - 14).

Comparison Of Gender, Age And Race

The overall adverse experience profile of KEPPRA 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

In addition to the adverse experiences listed above, the following have been reported in patients receiving marketed KEPPRA 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 KEPPRA use; recovery was observed in majority of cases where KEPPRA was discontinued. These adverse experiences have not been listed above, and data are insufficient to support an estimate of their incidence or to establish causation.

DRUG ABUSE AND DEPENDENCE

The abuse and dependence potential of KEPPRA has not been evaluated in human studies.



REPORTS OF SUSPECTED KEPPRA SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Keppra. The information is not vetted and should not be considered as verified clinical evidence.

Possible Keppra side effects / adverse reactions in 36 year old female

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 36 year old female weighing 104.0 kg (228.8 pounds)

Reactions: Petit MAL Epilepsy

Adverse event resulted in: hospitalization

Suspect drug(s):
Vimpat
    Administration route: Oral
    Start date: 2010-02-01
    End date: 2010-01-01

Keppra
    Administration route: Oral
    Indication: Convulsion
    Start date: 2010-02-15

Keppra
    Administration route: Oral
    Start date: 2010-02-15
    End date: 2010-02-15

Vimpat
    Administration route: Oral
    Indication: Convulsion
    Start date: 2010-10-26



Possible Keppra side effects / adverse reactions in 36 year old female

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 36 year old female weighing 104.0 kg (228.8 pounds)

Reactions: Pyrexia, Convulsion

Adverse event resulted in: hospitalization

Suspect drug(s):
Keppra
    Administration route: Oral
    Start date: 2010-02-15

Keppra
    Administration route: Oral
    Indication: Epilepsy
    Start date: 2010-02-15

Vimpat
    Administration route: Oral
    Start date: 2010-02-10

Vimpat
    Administration route: Oral
    Indication: Convulsion
    Start date: 2010-10-26

Other drugs received by patient: Zonisamide; Carbamazepine; Clonazepam; Phenytoin; Topiramate



Possible Keppra side effects / adverse reactions in 9 month old female

Reported by a pharmacist from Portugal on 2011-10-03

Patient: 9 month old female

Reactions: Incorrect Dose Administered

Suspect drug(s):
Keppra



See index of all Keppra side effect reports >>

Drug label data at the top of this Page last updated: 2009-05-11

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