Levetiracetam

Other Drug Interactions

Oral Contraceptives

Levetiracetam (500 mg twice daily) did not influence the pharmacokinetics of an oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, or of the luteinizing hormone and progesterone levels, indicating that impairment of contraceptive efficacy is unlikely. Coadministration of this oral contraceptive did not influence the pharmacokinetics of levetiracetam.

Digoxin

Levetiracetam (1000 mg twice daily) did not influence the pharmacokinetics and pharmacodynamics (ECG) of digoxin given as a 0.25 mg dose every day. Coadministration of digoxin did not influence the pharmacokinetics of levetiracetam.

Warfarin

Levetiracetam (1000 mg twice daily) did not influence the pharmacokinetics of R and S warfarin. Prothrombin time was not affected by levetiracetam. Coadministration of warfarin did not affect the pharmacokinetics of levetiracetam.

Probenecid

Probenecid, a renal tubular secretion blocking agent, administered at a dose of 500 mg four times a day, did not change the pharmacokinetics of levetiracetam 1000 mg twice daily. C^ss _max of the metabolite, ucb L057, was approximately doubled in the presence of probenecid while the fraction of drug excreted unchanged in the urine remained the same. Renal clearance of ucb L057 in the presence of probenecid decreased 60%, probably related to competitive inhibition of tubular secretion of ucb L057. The effect of levetiracetam on probenecid was not studied.

Carcinogenesis & Mutagenesis & Impairment Of Fertility

Carcinogenesis

Rats were dosed with levetiracetam in the diet for 104 weeksat doses of 50, 300 and 1800 mg/kg/day. The highest dose corresponds to 6 timesthe maximum recommended daily human dose (MRHD) of 3000 mg on a mg/m² basis andit also provided systemic exposure (AUC) approximately 6 times that achieved inhumans receiving the MRHD. There was no evidence of carcinogenicity. A studywas conducted in which mice received levetiracetam in the diet for 80 weeks atdoses of 60, 240 and 960 mg/kg/day (high dose is equivalent to 2 times the MRHDon a mg/m²or exposure basis). Although no evidence for carcinogenicity was seen, thepotential for a carcinogenic response has not been fully evaluated in thatspecies because adequate doses have not been studied.

Mutagenesis

Levetiracetam was not mutagenic in the Ames test or inmammalian cells in vitro in the Chinese hamsterovary/HGPRT locus assay. It was not clastogenic in an invitro analysis of metaphase chromosomes obtained from Chinese hamsterovary cells or in an in vivo mouse micronucleusassay. The hydrolysis product and major human metabolite of levetiracetam (ucbL057) was not mutagenic in the Ames test or the in vitromouse lymphoma assay.

Impairment Of Fertility

No adverse effects on male or female fertility orreproductive performance were observed in rats at doses up to 1800 mg/kg/day(approximately 6 times the maximum recommended human dose on a mg/m² or exposurebasis).

Pregnancy

TeratogenicEffects:

Pregnancy Category C

In animal studies, levetiracetam produced evidence ofdevelopmental toxicity at doses similar to or greater than human therapeuticdoses.

Treatmentof pregnant rabbits during the period of organogenesis resulted in increasedembryofetal mortality and increased incidences of minor fetal skeletalabnormalities at doses ≥600 mg/kg/day (approximately 4 times MRHD on a mg/m² basis) andin decreased fetal weights and increased incidences of fetal malformations at adose of  1800 mg/kg/day (12 times theMRHD on a mg/m^{2 basis). The developmental no effect dose was 200 mg/kg/day (1.3 times theMRHD on a mg/m2basis). Maternal toxicity was also observed at 1800 mg/kg/day.}

Whenpregnant rats were treated during the period of organogenesis, fetal weightswere decreased and the incidence of fetal skeletal variations was increased ata dose of 3600 mg/kg/day (12 times the MRHD). 1200mg/kg/day (4 times the MRHD) was a developmental no effect dose. There was noevidence of maternal toxicity in this study.

Treatmentof rats during the last third of gestation and throughout lactation produced noadverse developmental or maternal effects at doses of up to 1800 mg/kg/day (6times the MRHD on a mg/m^{2 basis).}

Thereare no adequate and well-controlled studies in pregnant women. Levetiracetam should be used during pregnancy only ifthe potential benefit justifies the potential risk to the fetus.

Pregnancy Registry

To provide information regardingthe effects of in utero exposure to levetiracetam, physicians are advised torecommend that pregnant patients taking levetiracetam enroll in the NorthAmerican Antiepileptic Drug (NAAED) pregnancy registry. This can be done bycalling the toll free number 1-888-233-2334, and must be done by the patientsthemselves. Informationontheregistry can also be found at the website http://www.aedpregnacyregistry.org/.

Labor & Delivery

Nursing Mothers

Pediatric Use

Safety and effectiveness in patients below 4 years of agehave not been established.

Studiesof levetiracetam in juvenile rats (dosing from day 4 through day 52 of age) anddogs (dosing from week 3 through week 7 of age) at doses of up to 1800mg/kg/day (approximately 7 and 24 times, respectively, the maximum recommendedpediatric dose of 60 mg/kg/day on a mg/m² basis) did not indicate apotential for age-specific toxicity.

Geriatric Use

Astudy in 16 elderly subjects (age 61 to 88 years) with oral administration ofsingle dose and multiple twice-daily doses for 10 days showed nopharmacokinetic differences related to age alone.

Levetiracetamis known to be substantially excreted by the kidney, and the risk of adversereactions to this drug may be greater in patients with impaired renal function.Because elderly patients are more likely to have decreased renal function, careshould be taken in dose selection, and it may be useful to monitor renalfunction.

Use In Patients With Impaired Renal Function

Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance. Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing hemodialysis. The dosage should be reduced in patients with impaired renal function receiving levetiracetam and supplemental doses should be given to patients after dialysis (see CLINICAL PHARMACOLOGYand DOSAGE AND ADMINISTRATION, Adult Patients with Impaired Renal Function).

LEVETIRACETAM ADVERSE REACTIONS

The prescriber should be awarethat the adverse event incidence figures in the following tables, obtained whenlevetiracetam was added to concurrent AED therapy,cannot be used to predict the frequency of adverse experiences in the course ofusual medical practice where patient characteristics and other factors maydiffer from those prevailing during clinical studies. Similarly, the citedfrequencies cannot be directly compared with figures obtained from otherclinical investigations involving different treatments, uses, or investigators.An inspection of these frequencies, however, does provide the prescriber withone basis to estimate the relative contribution of drug and non-drug factors tothe adverse event incidences in the population studied.

Partial Onset Seizures

In well-controlled clinical studies in adults with partialonset seizures, the most frequently reported adverse events associated with theuse of levetiracetam in combination with other AEDs, not seen at an equivalentfrequency among placebo-treated patients, were somnolence, asthenia, infectionand dizziness. In the well-controlled pediatric clinical study in children 4 to16 years of age with partial onset seizures, the adverse events most frequentlyreported with the use of levetiracetam in combination with other AEDs, not seenat an equivalent frequency among placebo-treated patients, were somnolence,accidental injury, hostility, nervousness, and asthenia.

Table8 lists treatment-emergent adverse events that occurred in at least 1% of adultepilepsy patients treated with levetiracetamparticipating in placebo-controlled studies and were numerically more commonthan in patients treated with placebo. Table 9 lists treatment-emergent adverseevents that occurred in at least 2% of pediatric epilepsy patients (ages 4 to16 years) treated with levetiracetam participatingin the placebo-controlled study and were numerically more common than inpediatric patients treated with placebo. In these studies, either levetiracetam or placebo was added to concurrent AEDtherapy. Adverse events were usually mild to moderate in intensity.

Table 8: Incidence (%) Of Treatment-EmergentAdverse Events In Placebo-Controlled, Add-On Studies In Adults Experiencing PartialOnset Seizures By Body System (Adverse Events Occurred In At Least 1% Of Levetiracetam-TreatedPatients And Occurred More Frequently Than Placebo-Treated Patients)

Otherevents reported by at least 1% of adult levetiracetam-treatedpatients 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, druglevel increased, dyspepsia, ecchymosis, fever, flu syndrome, fungal infection,gastroenteritis, gingivitis, grand mal convulsion, insomnia, nausea, otitismedia, rash, thinking abnormal, tremor, urinary tract infection, vomiting andweight gain.

Table 9: Incidence (%) Of Treatment-EmergentAdverse Events In A Placebo-Controlled, Add-On Study In Pediatric Patients Ages4 to 16 Years Experiencing Partial Onset Seizures By Body System (Adverse EventsOccurred In At Least 2% Of Levetiracetam-TreatedPatients And Occurred More Frequently Than Placebo-Treated Patients)

Myoclonic Seizures

Although the pattern of adverse events in this study seemssomewhat different from that seen in patients with partial seizures, this islikely due to the much smaller number of patients in this study compared topartial seizure studies. The adverse event pattern for patients with JME isexpected to be essentially the same as for patients with partial seizures.

In the well-controlled clinical study that included bothadolescent (12 to 16 years of age) and adult patients with myoclonic seizures,the most frequently reported adverse events associated with the use of levetiracetam in combinationwith other AEDs, not seen at an equivalent frequency among placebo-treatedpatients, were somnolence, neck pain, and pharyngitis.

Table 10 lists treatment-emergent adverse events that occurredin at least 5% of juvenile myoclonic epilepsy patients experiencing myoclonicseizures treated with levetiracetam and were numerically more common than in patients treatedwith placebo. In this study, either levetiracetam or placebo was added to concurrent AED therapy. Adverseevents were usually mild to moderate in intensity.

Table 10: Incidence (%) Of  Treatment-Emergent Adverse Events In APlacebo-Controlled, Add-On Study In Patients 12 Years Of Age And Older WithMyoclonic Seizures By Body System (Adverse Events Occurred In At Least 5% Of Levetiracetam-TreatedPatients And Occurred More Frequently Than Placebo-Treated Patients)

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

Primary Generalized Tonic-Clonic Seizures

 In the well-controlled clinical study that includedpatients 4 years of age and older with primary generalized tonic-clonic (PGTC)seizures, the most frequently reported adverse event associated with the use oflevetiracetam incombination with other AEDs, not seen at an equivalent frequency amongplacebo-treated patients, was nasopharyngitis.

Table 11 lists treatment-emergent adverseevents that occurred in at least 5% of idiopathic generalized epilepsy patientsexperiencing PGTC seizures treated with levetiracetamand were numerically more common than in patients treated with placebo. In thisstudy, either levetiracetam or placebo was addedto concurrent AED therapy. Adverse events were usually mild to moderate inintensity.

Table 11: Incidence (%) Of Treatment-Emergent Adverse Events In APlacebo-Controlled, Add-On Study In Patients 4 Years Of Age And Older With PGTCSeizures By MedDRA System Organ Class (Adverse Events Occurred In At Least 5%Of Levetiracetam-Treated Patients And Occurred More Frequently ThanPlacebo-Treated Patients)

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

Time Course Of Onset Of Adverse Events For Partial Onset Seizures

Discontinuation Or Dose Reduction In Well-Controlled Clinical Studies

In well-controlled adult clinical studies, 15.0% of patientsreceiving levetiracetam and 11.6% receivingplacebo either discontinued or had a dose reduction as a result of an adverseevent. Table 12 lists the most common (>1%) adverse events that resulted indiscontinuation or dose reduction.

Table 13: Adverse Events Most CommonlyAssociated With Discontinuation Or Dose Reduction In The Placebo-ControlledStudy In Pediatric Patients Ages 4 to 16 Years Experiencing Partial OnsetSeizures

Myoclonic Seizures

In the placebo-controlled study, 8.3%of patients receiving levetiracetam and 1.7% receiving placebo eitherdiscontinued or had a dose reduction as a result of an adverse event. Theadverse events that led to discontinuation or dose reduction in thewell-controlled study are presented in Table 14.

Table 14: Adverse Events That Resulted In Discontinuation Or DoseReduction In The Placebo-Controlled Study In Patients With Juvenile MyoclonicEpilepsy

PrimaryGeneralized Tonic-Clonic Seizures

In the placebo-controlled study, 5.1% of patients receivinglevetiracetam and 8.3% receiving placebo either discontinued or had a dosereduction during the treatment period as a result of a treatment-emergent adverseevent.

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

Comparison Of Gender, Age And Race

Postmarketing Experience

Thefollowing adverse events have been identified during postapproval use oflevetiracetam. Because these events are reported voluntarily from a populationof uncertain size, it is not always possible to reliably estimate theirfrequency 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 suppressionidentified in some of these cases), thrombocytopenia, and weight loss. Alopeciahas been reported with levetiracetam use; recoverywas observed in majority of cases where levetiracetamwas discontinued. These adverse experiences have not been listed above, anddata are insufficient to support an estimate of their incidence or to establishcausation.

DRUG ABUSE AND DEPENDENCE

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

CONTROLLED SUBSTANCE

OVERDOSAGE

Signs, Symptoms And Laboratory Findings Of Acute Overdosage In Humans

The highest known dose of levetiracetamreceived in the clinical development program was 6000 mg/day. Other thandrowsiness, there were no adverse events in the few known cases of overdose inclinical trials. Cases of somnolence, agitation, aggression, depressed level ofconsciousness, respiratory depression and coma were observed with levetiracetam overdoses in postmarketing use.

Treatment Or Management Of Overdose

There is no specific antidote for overdose with levetiracetam. If indicated, elimination of unabsorbeddrug should be attempted by emesis or gastric lavage; usual precautions shouldbe observed to maintain airway. General supportive care of the patient isindicated including monitoring of vital signs and observation of the patient’sclinical status. A CertifiedPoison ControlCenter should becontacted for up to date information on the management of overdose with levetiracetam.

Hemodialysis

Standard hemodialysis procedures result in significantclearance of levetiracetam (approximately 50% in 4 hours) and should be consideredin cases of overdose. Although hemodialysis has not been performed in the fewknown cases of overdose, it may be indicated by the patient's clinical state orin patients with significant renal impairment.

DOSAGE & ADMINISTRATION

Levetiracetam Tablet isindicated as adjunctive treatment of partial onset seizures in adults andchildren 4 years of age and older with epilepsy.

Levetiracetam Tablet isindicated as adjunctive therapy in the treatment of myoclonic seizures inadults and adolescents 12 years of age and older with juvenile myoclonicepilepsy.

Partial Onset Seizures

Adults 16 Years And Older

In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose (see CLINICAL STUDIES), a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients Ages 4 To <16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 52 mg/kg. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. Table 15 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

 Levetiracetam is given orally with or without food.

Table 15: Levetiracetam Tablet Weight-Based Dosing Guide For Children

The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients based on a daily dose of 20 mg/kg/day, 40 mg/kg/day or  60 mg/kg/day:

Total daily dose (mL/day) = Daily dose (mg/kg/day) x patient weight (kg)         

                                                                  100 mg/mL

 A household teaspoon or tablespoon is not an adequate measuring device. It is recommended that a calibrated measuring device be obtained and used. Healthcare providers should recommend a device that can measure and deliver the prescribed dose accurately, and provide instructions for measuring the dosage.

Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy

Treatment should beinitiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID).Dosage should be increased by 1000 mg/day every 2 weeks to the recommended dailydose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not beenstudied.

Primary Generalized Tonic-Clonic Seizures

Adults 16 Years and Older

Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. See Table 14 for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

Adult Patients With Impaired Renal Function

Levetiracetam dosing must beindividualized according to the patient's renal function status. Recommendeddoses and adjustment for dose for adults are shown in Table 16. To use thisdosing table, an estimate of the patient's creatinine clearance (CLcr) inmL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL)determination using the following formula:

              [140-age(years)] x weight (kg)
CLcr = ———————————————— (x 0.85 for female patients)
                 72x serum creatinine (mg/dL)

Table 16: Dosing Adjustment Regimen For AdultPatients With  Impaired Renal Function

¹Following dialysis, a 250 to 500 mg supplementaldose is recommended.

HOW SUPPLIED

Levetiracetam tablets, 250 mg are blue coloured, oblong shaped, scored, film coated tablets debossed with ‘H’ on one side and ‘87’ on other side. They are supplied in containers of

 30 tablets (NDC 65977-5036-0)

 60 tablets (NDC 65977-5036-1)

 120 tablets (NDC 65977-5036-2)

 500 tablets (NDC 65977-5036-3)

 1000 tablets (NDC 65977-5036-4)

 Levetiracetam tablets, 500 mg are yellow coloured, oblong shaped, scored, film coated tablets debossed with ‘H’ on one side and ‘88’ on other side. They are supplied in  containers of

 30 tablets (NDC 65977-5037-0)

 60 tablets (NDC 65977-5037-1)

 120 tablets (NDC 65977-5037-2)

 500 tablets (NDC 65977-5037-3)

 1000 tablets (NDC 65977-5037-4)

Levetiracetam tablets, 750 mg are orange coloured, oblong shaped, scored, film coated tablets debossed with ‘H’ on one side and ‘90’ on other side. They are supplied in containers of

 30 tablets (NDC 65977-5038-0)

 60 tablets (NDC 65977-5038-1)

120 tablets (NDC 65977-5038-2)

500 tablets (NDC 65977-5038-3)

30 tablets (NDC 65977-5039-0)

60 tablets (NDC 65977-5039-1)

120 tablets (NDC 65977-5039-2)

500 tablets (NDC 65977-5039-3)

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container.

ANIMAL PHARMACOLOGY & OR TOXICOLOGY

SPL MEDGUIDE

MEDICATION GUIDE

 Levetiracetam Tablets

 Rx Only

Read this Medication Guidebefore you start taking levetiracetam and each time you get a refill. There may be new information. This informationdoes not take the place of talkingto your healthcare provider about your medical condition or treatment

 What is the most important information I shouldknow about levetiracetam?

 Like other antiepileptic drugs, levetiracetam may cause suicidal thoughts or actions in a very smallnumber of people, about 1 in 500 people taking it.

Call a healthcareprovider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

•      thoughts about suicide or dying

•      attempts to commitsuicide

•      new or worsedepression

•      new or worse anxiety

•      feeling agitated orrestless

•      panic attacks

•      trouble sleeping(insomnia)

•      new or worseirritability

•      acting aggressive,being angry, or violent

•      acting on dangerous impulses

•      an extremeincrease in activity and talking (mania)

•      other unusual changesin behavior or mood

Do not stop levetiracetam without first talking to a healthcare provider .

•      Stopping levetiracetamsuddenly can cause serious problems. Stopping aseizure medicine suddenly can cause seizures that will not stop (status epilepticus).

•      Suicidal thoughts or actions can be caused by things other than medicines.  If you have suicidal thoughts or actions,your healthcare provider may checkfor other causes.

 How canI watch for early symptoms of suicidal thoughts and actions?

•      Pay attention to any changes, especially sudden changes, in mood, behaviors,thoughts, or feelings.

•      Keep all follow-upvisits with your healthcare provideras scheduled.

•      Call your healthcare providerbetween visits as needed, especially if you are worried about symptoms.

 What is levetiracetam?

 •     partial onset seizures in people 4 years ofage and older with epilepsy

           •     myoclonic seizures in people 12 years ofage and older with juvenile myoclonic epilepsy

           •     primary generalized tonic-clonic seizuresin people 6 years of age and older with  certain types of generalized epilepsy.

 It is not known iflevetiracetam is safe or effectivein children under 4 years ofage.

Before taking your medicine,make sure you have received the correctmedicine. Comparethe name above with the name on your bottle and the appearance of your medicine with the description of levetiracetamprovided below. Contact your pharmacist immediately if you believe a dispensing error may have occurred.

Levetiracetamtablets, 250 mg are blue coloured, oblong shaped, scored, film coated tabletsdebossed with ‘H’ on one side and ‘87’ on other side.

Levetiracetamtablets, 500 mg are yellow coloured, oblong shaped, scored, film coated tabletsdebossed with ‘H’ on one side and ‘88’ on other side.

Levetiracetamtablets, 750 mg are orange coloured, oblong shaped, scored, film coated tabletsdebossed with ‘H’ on one side and ‘90’ on other side.

Levetiracetamtablets, 1000 mg are white coloured, oblong shaped, scored, film coated tabletsdebossed with ‘H’ on one side and ‘91’ on other side.

What should I tell my healthcare provider beforestarting levetiracetam?

Before taking levetiracetam, tell your healthcare provider about all of your medical conditions, including if you:

•     have or have had depression, mood problems or suicidal thoughts or behavior

•     have kidney problems

•    are pregnant or planning to become pregnant. It is not known if levetiracetam  will harm your unborn baby. You and your healthcare provider will have to decide if you shouldtake levetiracetam while you are pregnant.  If you  become pregnant while taking levetiracetam, talk to your healthcare provider about registering with the NorthAmerican Antiepileptic Drug Pregnancy Registry. You can enroll in this registryby calling 1-888-233-2334. The  purpose of this registry is tocollect information about the safety of  levetiracetam and otherantiepileptic medicine during the pregnancy.

•     are breast feeding.Levetiracetam can pass into your milk and may harm your baby. You and your healthcare provider should discusswhether you should take levetiracetam or breast-feed; you should not do both.

Tell your healthcare providerabout all the medicines you take, including prescription and nonprescription medicines,vitamins, and herbalsupplements.  Do not start a new medicine without first talking with your healthcare provider.

Know the medicinesyou take.   Keepa list of them to show your healthcare providerand pharmacist each time you get a new medicine.

How shouldI take levetiracetam?

•   Your healthcare provider will tell you how much levetiracetam to take and when to take it.Levetiracetam is usually taken twicea day.  Take levetiracetam at the same times each day.

•     Your healthcare providermay change your dose. Do not changeyour dose without talking to your healthcareprovider.

•     Take levetiracetam with or without food.

•     Swallow the tabletswhole. Do not chew or crush tablets.

•     If you miss a dose of levetiracetam, take it as soon as you remember. If it is almost time foryour next dose, just skip the missed dose. Take the next dose at your regular time. Do not take two doses at the same time.

•     If you take too much levetiracetam, call your local Poison Control Center or go to the nearest emergency room right away.

 What should I avoid while taking levetiracetam?

 Do  not  drive, operate machinery  or  do  other  dangerous  activities  until  you  know howlevetiracetam affects you. Levetiracetam maymake you dizzy or sleepy.

What are the possible side effects oflevetiracetam?

•      See “What is the mostimportant information I should know about levetiracetam?”

Levetiracetam can cause serious side effects.

Call your healthcare provider right away if you haveany of these symptoms:

•  moodand behavior changessuch as aggression, agitation, anger, anxiety, apathy,mood swings, depression, hostility,and irritability.  A few people may get psychoticsymptoms such as hallucinations (seeing or hearing things that are really not there),delusions (false or strangethoughts or beliefs) and unusual behavior.

•    extreme sleepiness, tiredness, and weakness

•    problems with musclecoordination (problems walking andmoving)

The most common side effects seen in people whotake levetiracetam include:

•   sleepiness

•   weakness

•   dizziness

•   infection

The mostcommon side effects seen in childrenwho take levetiracetam include, in addition to those listed above:

•    accidental injury

•    irritability

•   hostility

These side effects can happen at any time but happen more often within thefirst 4 weeks of treatment except forinfection.

Tell your healthcare provider if you have any sideeffect that bothers you or that does not go away.

These are not all the possible side effects of levetiracetam.  For more information, ask your healthcareprovideror pharmacist.

Call your doctor for medical adviceabout side effects. You may reportside effects to FDA at 1-800-FDA-1088.

How should I store levetiracetam?

•    Store levetiracetam at room temperature, 20°C to 25°C (68°F to 77°F) awayfrom heat and light.

•    Keeplevetiracetam and all medicines out ofthe reach of children.

Generalinformation about levetiracetam.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.  Do not use levetiracetam for a condition for which it was not prescribed.Do not give levetiracetam to other people,even if they have the same symptoms that you have. It may harmthem.

This Medication Guide summarizes the most important information about levetiracetam. If you would like more information,talk with your healthcare provider.You can ask your pharmacist orhealthcare provider for information about levetiracetam that is writtenfor health professionals.

What are the ingredientsof levetiracetam?

Levetiracetam tablet active ingredient: levetiracetam

Inactive ingredients: corn starch, croscarmellose sodium, povidone, colloidal silicon dioxide, talc, magnesium stearate and additional agents listed below:

500mg tablets: opadry II yellow (polyvinyl alcohol, titanium dioxide, polyethyleneglycol 3350, talc, iron oxide yellow)

750mg tablets:  opadry II orange (polyvinylalcohol, titanium dioxide,  polyethyleneglycol 3350, talc, FD&C yellow #6/sunset yellow FCF aluminum lake, ironoxide red)

1000mg tablets: opadry II white (polyvinyl alcohol, titanium dioxide, polyethyleneglycol 3350, talc)

Levetiracetamdoes not contain lactose or gluten.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL