LEVETIRACETAM - levetiracetam tablet, film coated
Aurobindo Pharma Limited
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use levetiracetam tablets safely and effectively. See full prescribing information for levetiracetam tablets USP.
Levetiracetam Tablets USP for Oral Use Initial U.S. Approval: 1999 RECENT MAJOR CHANGESINDICATIONS AND USAGELevetiracetam is an antiepileptic drug indicated for adjunctive therapy in the treatment of: DOSAGE AND ADMINISTRATION
Partial Onset Seizures
Myoclonic Seizures In Adults and Pediatric Patients 12 Years And Older
Primary Generalized Tonic-Clonic Seizures
Adult Patients with Impaired Renal Function DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
ADVERSE REACTIONSMost common adverse reactions (incidence in levetiracetam-treated patients is ≥ 5% more than in placebo-treated patients) include:
To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONS
Information describing the use of levetiracetam tablets in pediatric patients less than 4 years of age as adjunctive therapy in the treatment of partial onset seizures is approved for UCB, Inc.’s levetiracetam tablets. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Revised: 01/2013 |
Levetiracetam tablets USP are indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.
Information describing the use of levetiracetam in pediatric patients less than 4 years of age as adjunctive therapy in the treatment of partial onset seizures is approved for UCB, Inc.’s levetiracetam tablets. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Levetiracetam tablets are given orally with or without food. The levetiracetam dosing regimen depends on the indication, age group, dosage form (tablets or oral solution), and renal function.
Prescribe the oral solution for pediatric patients with body weight ≤ 20 kg. Prescribe the oral solution or tablets for pediatric patients with body weight above 20 kg.
When using the oral solution in pediatric patients, dosing is weight-based (mg per kg) using a calibrated measuring device (not a household teaspoon or tablespoon).
Levetiracetam tablets should be swallowed whole. Levetiracetam tablets should not be chewed or crushed.
Then CLcr is adjusted for body surface area (BSA) as follows:
CLcr (mL/min)
CLcr (mL/min/1.73 m2) = -------------------------- x 1.73
BSA subject (m2)
Group | Creatinine Clearance (mL/min/1.73 m2) | Dosage (mg) | Frequency |
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1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. |
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Normal | > 80 | 500 to 1,500 | Every 12 hours |
Mild | 50 – 80 | 500 to 1,000 | Every 12 hours |
Moderate | 30 – 50 | 250 to 750 | Every 12 hours |
Severe | < 30 | 250 to 500 | Every 12 hours |
ESRD patients using dialysis | ---- | 500 to 1,0001
| Every 24 hours1
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In some patients levetiracetam causes behavioral abnormalities. The incidences of behavioral abnormalities in the myoclonic and primary generalized tonic-clonic seizure studies were comparable to those of the adult and pediatric partial onset seizure studies.
A total of 13.3% of adult levetiracetam-treated patients and 37.6% of pediatric levetiracetam-treated patients (4 to 16 years of age) compared to 6.2% and 18.6% of adult and pediatric placebo patients respectively, experienced non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personality disorder). A randomized double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of levetiracetam as adjunctive therapy in pediatric patients (4 to 16 years of age). The results from an exploratory analysis indicated a worsening in levetiracetam-treated patients on aggressive behavior (one of eight behavior dimensions) as measured in a standardized and systematic way using a validated instrument, the Achenbach Child Behavior Checklist (CBCL/6 to 18).
In pediatric patients 1 month to < 4 years of age, irritability was reported in 11.7% of the levetiracetam-treated patients compared to 0% of placebo patients.
A total of 1.7% of adult levetiracetam-treated patients discontinued treatment due to behavioral adverse events, compared to 0.2% of placebo patients. The treatment dose was reduced in 0.8% of adult levetiracetam-treated patients and in 0.5% of placebo patients. Overall, 10.9% of levetiracetam-treated pediatric patients experienced behavioral symptoms associated with discontinuation or dose reduction, compared to 6.2% of placebo patients.
Indication | Placebo Patients with Events Per 1000 Patients | Drug Patients with Events Per 1000 Patients | Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients | Risk Difference: Additional Drug Patients with Events Per 1000 Patients |
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Epilepsy | 1 | 3.4 | 3.5 | 2.4 |
Psychiatric | 5.7 | 8.5 | 1.5 | 2.9 |
Other | 1 | 1.8 | 1.9 | 0.9 |
Total | 2.4 | 4.3 | 1.8 | 1.9 |
Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults treated with levetiracetam. The median time of onset is reported to be 14 to 17 days, but cases have been reported at least four months after initiation of treatment. Recurrence of the serious skin reactions following rechallenge with levetiracetam has also been reported. Levetiracetam should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered.
In the controlled cognitive and neuropsychological safety study, two subjects (6.1%) in the placebo group and 5 subjects (8.6%) in the levetiracetam-treated group had high eosinophil count values that were possibly clinically significant (≥10% or ≥0.7 x 109/L).
Juvenile Myoclonic Epilepsy
In a randomized, placebo-controlled study in patients aged 1 month to <4 years of age, a significantly higher risk of at least one measured increase in diastolic blood pressure was observed in the levetiracetam-treated patients (17%) compared to the placebo-treated patients (2%). There was no overall difference in mean diastolic blood pressure between the treatment groups. This disparity between the levetiracetam and placebo treatment groups was not observed in the studies of older children or in adults.
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.
The following adverse reactions are discussed in more details in other sections of labeling:
Body System/ Adverse Reaction | Levetiracetam (N=769) % | Placebo (N=439) % |
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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 |
Adverse Reaction | Levetiracetam (N=769) % | Placebo (N=439) % |
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Dizziness | 1 | 0 |
Somnolence | 4 | 2 |
Body System/ Adverse Reaction | Levetiracetam (N=165) % | Placebo (N=131) % |
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Ear and Labyrinth Disorders
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Ear Pain | 2 | 1 |
Eye Disorders
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Conjunctivitis | 2 | 0 |
Gastrointestinal Disorders
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Vomiting | 15 | 12 |
Abdominal Pain Upper | 9 | 8 |
Diarrhea | 6 | 5 |
Constipation | 3 | 1 |
General Disorders and Administration Site Conditions
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Fatigue | 11 | 5 |
Infections and Infestations
| |
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Nasopharyngitis | 15 | 12 |
Influenza | 3 | 1 |
Gastroenteritis | 2 | 0 |
Rhinitis | 2 | 0 |
Injury, Poisoning and Procedural Complications
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Head Injury | 4 | 0 |
Contusion | 3 | 1 |
Fall | 3 | 2 |
Joint Sprain | 2 | 1 |
Metabolism and Nutrition Disorders
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Decreased Appetite | 8 | 2 |
Anorexia | 4 | 3 |
Musculoskeletal and Connective Tissue Disorders
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Arthralgia | 2 | 0 |
Neck Pain | 2 | 1 |
Nervous System
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Headache | 19 | 15 |
Somnolence | 13 | 9 |
Dizziness | 7 | 5 |
Lethargy | 6 | 2 |
Sedation | 2 | 1 |
Psychiatric Disorders
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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 |
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.
Body System/ Adverse Reaction | Levetiracetam (N=60) % | Placebo (N=60) % |
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Ear and Labyrinth Disorders
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Vertigo | 5 | 3 |
Infections and Infestations
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Pharyngitis | 7 | 0 |
Influenza | 5 | 2 |
Musculoskeletal and Connective Tissue Disorders
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Neck Pain | 8 | 2 |
Nervous System Disorders
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Somnolence | 12 | 2 |
Psychiatric Disorders
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Depression | 5 | 2 |
Adverse Reaction | Levetiracetam (N=60) % | Placebo (N=60) % |
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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 |
Body System/ Adverse Reaction | Levetiracetam (N=79) % | Placebo (N=84) % |
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Gastrointestinal Disorders
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Diarrhea | 8 | 7 |
General Disorders and Administration Site Conditions
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Fatigue | 10 | 8 |
Infections and Infestations
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Nasopharyngitis | 14 | 5 |
Psychiatric Disorders
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Irritability | 6 | 2 |
Mood Swings | 5 | 1 |
Placebo (N=95) | Levetiracetam 1000 mg/day (N=97) | Levetiracetam 3000 mg/day (N=101) |
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*statistically significant versus placebo |
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Percent reduction in partial seizure frequency over placebo | – | 26.1%* | 30.1%* |
The percentage of patients (y-axis) who achieved ≥50% reduction in weekly seizure rates from baseline in partial onset seizure frequency over the entire randomized treatment period (titration + evaluation period)within the three treatment groups (x-axis) is presented in Figure 1.
Study 2
Study 2 was a double-blind, placebo-controlled, crossover study conducted at 62 centers in Europe comparing levetiracetam 1000 mg/day (N=106), levetiracetam 2000 mg/day (N=105), and placebo (N=111) given in equally divided doses twice daily.
Placebo (N=111) | Levetiracetam 1000 mg/day (N=106) | Levetiracetam 2000 mg/day (N=105) |
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*statistically significant versus placebo |
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Percent reduction in partial seizure frequency over placebo | – | 17.1%* | 21.4%* |
The comparison of levetiracetam 2000 mg/day to levetiracetam 1000 mg/day for responder rate was statistically significant (P=0.02). Analysis of the trial as a cross-over yielded similar results.
Placebo (N=104) | Levetiracetam 3000 mg/day (N=180) |
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*statistically significant versus placebo |
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Percent reduction in partial seizure frequency over placebo | – | 23%* |
The percentage of patients (y-axis) who achieved ≥50% reduction in weekly seizure rates from baseline in partial onset seizure frequency over the entire randomized treatment period (titration + evaluation period) within the two treatment groups (x-axis) is presented in Figure 3.
Effectiveness In Partial Onset Seizures In Pediatric Patients 4 Years To 16 Years With Epilepsy
Placebo (N=97) | Levetiracetam (N=101) | |
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*statistically significant versus placebo |
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Percent reduction in partial seizure frequency over placebo | - | 26.8%* |
The percentage of patients (y-axis) who achieved ≥ 50% reduction in weekly seizure rates from baseline in partial onset seizure frequency over the entire randomized treatment period (titration + evaluation period) within the two treatment groups (x-axis) is presented in Figure 4.
Clinical trial information in pediatric patients less than 4 years of age as adjunctive therapy in the treatment of partial onset seizures is approved for UCB, Inc.’s levetiracetam tablets. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Placebo (N=59) | Levetiracetam (N=54) |
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*statistically significant versus placebo |
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Percentage of responders | 23.7% | 60.4%* |
Placebo (N=84) | Levetiracetam (N=78) | |
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*statistically significant versus placebo |
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Percent reduction in PGTC seizure frequency | 44.6% | 77.6%* |
The percentage of patients (y-axis) who achieved ≥50% reduction in weekly seizure rates from baseline in PGTC seizure frequency over the entire randomized treatment period (titration + evaluation period) within the two treatment groups (x-axis) is presented in Figure 6.
See FDA-approved Patient Labeling (Medication Guide).
Do not stop levetiracetam tablets without first talking to a healthcare provider.
How can I watch for early symptoms of suicidal thoughts and actions?
What are levetiracetam tablets?
Levetiracetam tablets are a prescription medicine taken by mouth that is used with other medicines to treat:
Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Do not start a new medicine without first talking with your healthcare provider.
What should I avoid while taking levetiracetam tablets?
The most common side effects seen in people who take levetiracetam tablets include:
The most common side effects seen in children who take levetiracetam tablets include, in addition to those listed above:
Information on the use of levetiracetam in pediatric patients less than 4 years of age as adjunctive therapy in the treatment of partial onset seizures is approved for UCB, Inc.’s levetiracetam tablets. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
LEVETIRACETAM
levetiracetam tablet, film coated |
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LEVETIRACETAM
levetiracetam tablet, film coated |
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LEVETIRACETAM
levetiracetam tablet, film coated |
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LEVETIRACETAM
levetiracetam tablet, film coated |
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Labeler - Aurobindo Pharma Limited (650082092) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
Aurobindo Pharma Limited | 918917642 | ANALYSIS(65862-245, 65862-246, 65862-247, 65862-315), MANUFACTURE(65862-245, 65862-246, 65862-247, 65862-315) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
Aurobindo Pharma Limited | 918917626 | API MANUFACTURE(65862-245, 65862-246, 65862-247, 65862-315) |