Levetiracetam

Levetiracetam is a white to off-white crystalline powder with a faint odor and a bitter taste. It is very soluble in water (104.0 g/100 mL). It is freely soluble in chloroform (65.3 g/100 mL) and in methanol (53.6 g/100 mL), soluble in ethanol (16.5 g/100 mL), sparingly soluble in acetonitrile (5.7 g/100 mL) and practically insoluble in n-hexane. (Solubility limits are expressed as g/100 mL solvent.)

Levetiracetam extended-release tablets USP contain the labeled amount of levetiracetam. Inactive ingredients: colloidal silicon dioxide, dibasic calcium phosphate anhydrous, hydrogenated vegetable oil, hypromellose, lactose anhydrous, magnesium stearate, polyvinyl alcohol, polyethylene glycol, talc and titanium dioxide. The imprinting ink contains shellac, iron oxide black and propylene glycol.

12. CLINICAL PHARMACOLOGY

12.1 Mechanism Of Action

The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. The antiepileptic activity of levetiracetam was assessed in a number of animal models of epileptic seizures. Levetiracetam did not inhibit single seizures induced by maximal stimulation with electrical current or different chemoconvulsants and showed only minimal activity in submaximal stimulation and in threshold tests. Protection was observed, however, against secondarily generalized activity from focal seizures induced by pilocarpine and kainic acid, two chemoconvulsants that induce seizures that mimic some features of human complex partial seizures with secondary generalization. Levetiracetam also displayed inhibitory properties in the kindling model in rats, another model of human complex partial seizures, both during kindling development and in the fully kindled state. The predictive value of these animal models for specific types of human epilepsy is uncertain.

In vitro and in vivo recordings of epileptiform activity from the hippocampus have shown that levetiracetam inhibits burst firing without affecting normal neuronal excitability, suggesting that levetiracetam may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity.

Levetiracetam at concentrations of up to 10 μM did not demonstrate binding affinity for a variety of known receptors, such as those associated with benzodiazepines, GABA (gamma-aminobutyric acid), glycine, NMDA (N-methyl-D-aspartate), re-uptake sites, and second messenger systems. Furthermore, in vitro studies have failed to find an effect of levetiracetam on neuronal voltage-gated sodium or T-type calcium currents and levetiracetam does not appear to directly facilitate GABAergic neurotransmission. However, in vitro studies have demonstrated that levetiracetam opposes the activity of negative modulators of GABA- and glycine-gated currents and partially inhibits N-type calcium currents in neuronal cells.

A saturable and stereoselective neuronal binding site in rat brain tissue has been described for levetiracetam. Experimental data indicate that this binding site is the synaptic vesicle protein SV2A, thought to be involved in the regulation of vesicle exocytosis. Although the molecular significance of levetiracetam binding to synaptic vesicle protein SV2A is not understood, levetiracetam and related analogs showed a rank order of affinity for SV2A which correlated with the potency of their antiseizure activity in audiogenic seizure-prone mice. These findings suggest that the interaction of levetiracetam with the SV2A protein may contribute to the antiepileptic mechanism of action of the drug.

12.2 Pharmacodynamics

Effects on QTc Interval

The effects of extended-release levetiracetam tablets on QTc prolongation is expected to be the same as that of immediate-release levetiracetam tablets. The effect of immediate-release levetiracetam tablets on QTc prolongation was evaluated in a randomized, double-blind, positive-controlled (moxifloxacin 400 mg) and placebo-controlled crossover study of immediate-release levetiracetam tablets (1000 mg or 5000 mg) in 52 healthy subjects. The upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc was below 10 milliseconds. Therefore, there was no evidence of significant QTc prolongation in this study.

12.3 Pharmacokinetics

Overview

Bioavailability of levetiracetam extended-release tablets is similar to that of the levetiracetam immediate release tablets. The pharmacokinetics (AUC and C_max) were shown to be dose proportional after single dose administration of 1000 mg, 2000 mg, and 3000 mg extended-release levetiracetam. Plasma half-life of extended-release levetiracetam is approximately 7 hours.

Levetiracetam is almost completely absorbed after oral administration. The pharmacokinetics of levetiracetam are linear and time-invariant, with low intra- and inter-subject variability. Levetiracetam is not significantly protein-bound (<10% bound) and its volume of distribution is close to the volume of intracellular and extracellular water. Sixty-six percent (66%) of the dose is renally excreted unchanged. The major metabolic pathway of levetiracetam (24% of dose) is an enzymatic hydrolysis of the acetamide group. It is not liver cytochrome P450 dependent. The metabolites have no known pharmacological activity and are renally excreted. Plasma half-life of levetiracetam across studies is approximately 6 to 8 hours. The half-life is increased in the elderly (primarily due to impaired renal clearance) and in subjects with renal impairment.

Absorption and Distribution

Extended-release levetiracetam peak plasma concentrations occur in about 4 hours. The time to peak plasma concentrations is about 3 hours longer with extended-release levetiracetam than with immediate-release tablets.

Single administration of two 500 mg extended-release levetiracetam tablets once daily produced comparable maximal plasma concentrations and area under the plasma concentration versus time as did the administration of one 500 mg immediate-release tablet twice daily in fasting conditions. After multiple dose extended-release levetiracetam tablets intake, extent of exposure (AUC_0-24) was similar to extent of exposure after multiple dose immediate-release tablets intake.   C_max and C_min were lower by 17% and 26% after multiple dose extended-release levetiracetam tablets intake in comparison to multiple dose immediate-release tablets intake. Intake of a high fat, high calorie breakfast before the administration of extended-release levetiracetam tablets resulted in a higher peak concentration, and longer median time to peak. The median time to peak (T_max) was 2 hours longer in the fed state.

Two 750 mg extended-release levetiracetam tablets were bioequivalent to a single administration of three 500 mg extended-release levetiracetam tablets.

Metabolism

Levetiracetam is not extensively metabolized in humans. The major metabolic pathway is the enzymatic hydrolysis of the acetamide group, which produces the carboxylic acid metabolite, ucb L057 (24% of dose) and is not dependent on any liver cytochrome P450 isoenzymes. The major metabolite is inactive in animal seizure models. Two minor metabolites were identified as the product of hydroxylation of the 2-oxo-pyrrolidine ring (2% of dose) and opening of the 2-oxo-pyrrolidine ring in position 5 (1% of dose). There is no enantiomeric interconversion of levetiracetam or its major metabolite.

Elimination

Levetiracetam plasma half-life in adults is 7 ± 1 hour and is unaffected by either dose or repeated administration. Levetiracetam is eliminated from the systemic circulation by renal excretion as unchanged drug which represents 66% of administered dose. The total body clearance is 0.96 mL/min/kg and the renal clearance is 0.6 mL/min/kg. The mechanism of excretion is glomerular filtration with subsequent partial tubular reabsorption. The metabolite ucb L057 is excreted by glomerular filtration and active tubular secretion with a renal clearance of 4 mL/min/kg. Levetiracetam elimination is correlated to creatinine clearance. Levetiracetam clearance is reduced in patients with impaired renal function [see Use in Specific Populations (8.6) and Dosage and Administration (2.1)].

Special Populations

Elderly:

There are insufficient pharmacokinetic data to specifically address the use of extended-release levetiracetam in the elderly population.

Pharmacokinetics of immediate-release levetiracetam were evaluated in 16 elderly subjects (age 61 to 88 years) with creatinine clearance ranging from 30 to 74 mL/min. Following oral administration of twice-daily dosing for 10 days, total body clearance decreased by 38% and the half-life was 2.5 hours longer in the elderly compared to healthy adults. This is most likely due to the decrease in renal function in these subjects.

Pediatric Patients:

Safety and effectiveness of extended-release levetiracetam tablets in patients below the age of 16 years have not been established.

Pregnancy

Extended-release levetiracetam tablets levels may decrease during pregnancy.

Gender:

Extended-release levetiracetam C_max was 21 to 30% higher and AUC was 8 to 18% higher in women (N=12) compared to men (N=12). However, clearances adjusted for body weight were comparable.

Race:

Formal pharmacokinetic studies of the effects of race have not been conducted with extended-release or immediate-release levetiracetam. Cross study comparisons involving Caucasians (N=12) and Asians (N=12), however, show that pharmacokinetics of immediate-release levetiracetam were comparable between the two races. Because levetiracetam is primarily renally excreted and there are no important racial differences in creatinine clearance, pharmacokinetic differences due to race are not expected.

Renal Impairment:

The effect of extended-release levetiracetam tablets on renally impaired patients was not assessed in the controlled study. However, it is expected that the effect on extended-release levetiracetam tablets-treated patients would be similar to that seen in controlled studies of immediate-release levetiracetam tablets. In patients with end stage renal disease on dialysis, it is recommended that immediate-release levetiracetam be used instead of extended-release levetiracetam tablets.

The disposition of immediate-release levetiracetam was studied in adult subjects with varying degrees of renal function. Total body clearance of levetiracetam is reduced in patients with impaired renal function by 40% in the mild group (CL_cr = 50 to 80 mL/min), 50% in the moderate group (CL_cr = 30 to 50 mL/min) and 60% in the severe renal impairment group (CL_cr <30 mL/min). Clearance of levetiracetam is correlated with creatinine clearance.

In anuric (end stage renal disease) patients, the total body clearance decreased 70% compared to normal subjects (CL_cr >80mL/min). Approximately 50% of the pool of levetiracetam in the body is removed during a standard 4 hour hemodialysis procedure.

Dosage should be reduced in patients with impaired renal function receiving levetiracetam; immediate-release levetiracetam should be given to patients on dialysis [see Dosage and Administration (2.1)].

Hepatic Impairment:

In subjects with mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment, the pharmacokinetics of levetiracetam were unchanged. In patients with severe hepatic impairment (Child-Pugh C), total body clearance was 50% that of normal subjects, but decreased renal clearance accounted for most of the decrease. No dose adjustment is needed for patients with hepatic impairment.

Drug Interactions:

In vitro data on metabolic interactions indicate that levetiracetam is unlikely to produce, or be subject to, pharmacokinetic interactions. Levetiracetam and its major metabolite, at concentrations well above C_max levels achieved within the therapeutic dose range, are neither inhibitors of, nor high affinity substrates for, human liver cytochrome P450 isoforms, epoxide hydrolase or UDP-glucuronidation enzymes. In addition, levetiracetam does not affect the in vitro glucuronidation of valproic acid.

Potential pharmacokinetic interactions of or with levetiracetam were assessed in clinical pharmacokinetic studies (phenytoin, valproate, warfarin, digoxin, oral contraceptive, probenecid) and through pharmacokinetic screening with immediate-release levetiracetam tablets in the placebo-controlled clinical studies in epilepsy patients. The potential for drug interactions for extended-release levetiracetam tablets is expected to be essentially the same as that with immediate-release levetiracetam tablets.

Phenytoin

Immediate-release levetiracetam tablets (3000 mg daily) had no effect on the pharmacokinetic disposition of phenytoin in patients with refractory epilepsy. Pharmacokinetics of levetiracetam were also not affected by phenytoin.

Valproate

Immediate-release levetiracetam tablets (1500 mg twice daily) did not alter the pharmacokinetics of valproate in healthy volunteers. Valproate 500 mg twice daily did not modify the rate or extent of levetiracetam absorption or its plasma clearance or urinary excretion. There also was no effect on exposure to and the excretion of the primary metabolite, ucb L057.

Other Antiepileptic Drugs

Potential drug interactions between immediate-release levetiracetam tablets and other AEDs (carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone and valproate) were also assessed by evaluating the serum concentrations of levetiracetam and these AEDs during placebo-controlled clinical studies. These data indicate that levetiracetam does not influence the plasma concentration of other AEDs and that these AEDs do not influence the pharmacokinetics of levetiracetam.

Oral Contraceptives

Immediate-release levetiracetam tablets (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

Immediate-release levetiracetam tablets (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

Immediate-release levetiracetam tablets (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 immediate-release levetiracetam tablets on probenecid was not studied.

13. NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Rats were dosed with levetiracetam in the diet for 104 weeks at doses of 50, 300 and 1800 mg/kg/day. The highest dose corresponds is 6 times the maximum recommended daily human dose (MRHD) of 3000 mg on a mg/m² basis and it also provided systemic exposure (AUC) approximately 6 times that achieved in humans receiving the MRHD. There was no evidence of carcinogenicity. In mice, oral administration of levetiracetam for 80 weeks (doses up to 960 mg/kg/day) or 2 years (doses up to 4000 mg/kg/day, lowered to 3000 mg/kg/day after 45 weeks due to intolerability) was not associated with an increase in tumors. The highest dose tested in mice for 2 years (3000 mg/kg/day) is approximately 5 times the MRHD on a mg/m²basis.

Mutagenesis

Levetiracetam was not mutagenic in the Ames test or in mammalian cells in vitro in the Chinese hamster ovary/HGPRT locus assay. It was not clastogenic in an in vitro analysis of metaphase chromosomes obtained from Chinese hamster ovary cells or in an in vivo mouse micronucleus assay. The hydrolysis product and major human metabolite of levetiracetam (ucb L057) was not mutagenic in the Ames test or the in vitro mouse lymphoma assay.

Impairment of Fertility

No adverse effects on male or female fertility or reproductive performance were observed in rats at oral doses up to 1800 mg/kg/day (6 times the maximum recommended human dose on a mg/m² or systemic exposure [AUC] basis).

14. CLINICAL STUDIES

The effectiveness of the immediate-release formulation of levetiracetam as adjunctive therapy (added to other antiepileptic drugs) in adults was established in three multicenter, randomized, double-blind, placebo controlled clinical studies in 904 patients who had refractory partial onset seizures with or without secondary generalization for at least two years and had taken two or more classical AEDs.

The effectiveness of levetiracetam extended-release tablets as adjunctive therapy (added to other antiepileptic drugs) was established in one multicenter, randomized, double-blind, placebo-controlled clinical study across 7 countries in patients who had refractory partial onset seizures with or without secondary generalization. Patients enrolled had at least eight partial seizures with or without secondary generalization during the 8-week baseline period and at least two partial seizures in each 4-week interval of the baseline period. Patients were taking a stable dose regimen of at least one and could take a maximum of three AEDs. After a prospective baseline period of 8 weeks, 158 patients were randomized to placebo (N=79) or extended-release levetiracetam tablets (2x500 mg tablets) (N=79) given once daily over a 12-week treatment period.

The primary efficacy endpoint was the percent reduction over placebo in mean weekly frequency of partial onset seizures. The median percent reduction in weekly partial onset seizure frequency from baseline over the treatment period was 46.1% in the levetiracetam extended-release tablets 1000 mg treatment group (N=74) and 33.4% in the placebo group (N=78). The estimated percent reduction over placebo in weekly partial onset seizure frequency over the treatment period was 14.4% (statistically significant).

The relationship between the effectiveness of the same daily dose of levetiracetam extended-release tablets and immediate-release levetiracetam has not been studied and is unknown.

16. HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Levetiracetam Extended-Release Tablets USP, 500 mg tablets are white to off white, oblong-shaped, biconvex, film coated tablets, imprinted ‘L008’ (in black ink) on one side and plain on the other side. They are supplied in white HDPE bottles containing 60 tablets (NDC 68180-117-07) and white HDPE bottles containing 500 tablets (NDC 68180-117-02).

Levetiracetam Extended-Release Tablets USP, 750 mg are white to off white, oblong-shaped, biconvex, film coated tablets, imprinted 'L009' (in black ink) on one side and plain on the other side. They are supplied in white HDPE bottles containing 60 tablets (NDC 68180-118-07) and white HDPE bottles containing 500 tablets (NDC 68180-118-02).

16.2 Storage

Store at 25°C (77°F); excursions permitted to 15 to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Pharmacist: Dispense in a tight, light-resistant container with a child-resistant closure.

17. PATIENT COUNSELING INFORMATION

See FDA-approved Patient Labeling (Medication Guide).

Counsel patients on the benefits and risks of receiving extended-release levetiracetam tablets. Provide the Medication Guide to patients and/or caregivers, and instruct them to read the Medication Guide prior to taking extended-release levetiracetam tablets. Instruct patients to take extended-release levetiracetam tablets only as prescribed.

Suicidal Behavior and Ideation

Counsel patients, their caregivers, and/or families that antiepileptic drugs (AEDs), including extended-release levetiracetam tablets, may increase the risk of suicidal thoughts and behavior and advise patients to be alert for the emergence or worsening of symptoms of depression; unusual changes in mood or behavior, or suicidal thoughts, behavior, or thoughts about self-harm. Advice patients, their caregivers, and/or families to immediately report behaviors of concern to a healthcare providers.

Psychiatric Reactions and Changes in Behavior

Advise patients that extended-release levetiracetam tablets may cause changes in behavior (e.g. irritability and aggression). In addition, patients should be advised that they may experience changes in behavior that have been seen with other formulations of levetiracetam, which include agitation, anger, anxiety, apathy, depression, hostility, and, in rare cases, psychotic symptoms.

Effects on Driving or Operating Machinery

Inform patients that extended-release levetiracetam tablets may cause dizziness and somnolence. Inform patients not to drive or operate machinery until they have gained sufficient experience on extended-release levetiracetam tablets to gauge whether it adversely affects their ability to drive or operate machinery.

Dermatological Adverse Reactions

Advise patients that serious dermatological adverse reactions have occurred in patients treated with levetiracetam and instruct them to call their physician immediately if a rash develops.

Dosing and Administration

Patients should be instructed to only take levetiracetam extended-release tablets as prescribed and to swallow the tablets whole. They should not be chewed, broken, or crushed.

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during extended-release levetiracetam tablets. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 [see Use in Specific Populations (8.1)].

Residual Inert Matrix Tablet

Patients receiving levetiracetam extended-release tablets may notice an inert matrix tablet passing in the stool. Patients should be informed that the active medication has already been absorbed by the time the patient sees the inert matrix tablet.

Manufactured By:

Lupin Limited

Goa 403 722 India

For BluePoint Laboratories

Rev 06/14

MEDICATION GUIDE

LEVETIRACETAM (LEE-ve-tye-RA-se-tam) EXTENDED-RELEASE TABLETS USP

Rx Only

Read the Patient Information that comes with levetiracetam extended-release tablets before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your condition or your treatment.

What is the most important information I should know about levetiracetam extended-release tablets?

Like other antiepileptic drugs, levetiracetam extended-release tablets may cause suicidal thoughts or actions in a very small number of people, about 1 in 500 people taking it.

Call a healthcare provider 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 commit suicide
• •new or worse depression
• •new or worse anxiety
• •feeling agitated or restless
• •panic attacks
• •trouble sleeping (insomnia)
• •new or worse irritability
• •acting aggressive, being angry, or violent
• •acting on dangerous impulses
• •an extreme increase in activity and talking (mania)
• •other unusual changes in behavior or mood

Do not stop levetiracetam extended-release tablets without first talking to a healthcare provider.

• •Stopping levetiracetam extended-release tablets suddenly can cause serious problems. Stopping a seizure 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 check for other causes.

How can I 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-up visits with your healthcare provider as scheduled.
• •Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

What are levetiracetam extended-release tablets?

Levetiracetam extended-release tablets are a prescription medicine taken by mouth that is used with other medicines to treat partial onset seizures in people 16 years of age and older with epilepsy.

It is not known if levetiracetam extended-release tablet is safe or effective in people under 16 years of age.

Before taking your medicine, make sure you have received the correct medicine. Compare the name above with the name on your bottle and the appearance of your medicine with the description of levetiracetam extended-release tablets provided below. Tell your pharmacist immediately if you think you have been given the wrong medicine.

500 mg levetiracetam extended-release tablets are white to off white, oblong-shaped, biconvex, film-coated tablets, imprinted "L008" (in black ink) on one side and plain on the other side.

750 mg levetiracetam extended-release tablets are white to off white, oblong-shaped, biconvex, film-coated tablets, imprinted "L009" (in black ink) on one side and plain on the other side.

What should I tell my healthcare provider before starting levetiracetam extended-release tablets?

Before taking levetiracetam extended-release tablets, 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 extended-release tablets will harm your unborn baby. You and your healthcare provider will have to decide if you should take levetiracetam extended-release tablets while you are pregnant. If you become pregnant while taking levetiracetam extended-release tablets, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of levetiracetam extended-release tablets and other antiepileptic medicine during pregnancy.
• •are breast feeding. Levetiracetam can pass into your milk and may harm your baby. You and your healthcare provider should discuss whether you should take levetiracetam extended-release tablets or breast feed; you should not do both.

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.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist each time you get a new medicine.

How should I take levetiracetam extended-release tablets?

Take levetiracetam extended-release tablets exactly as prescribed.

• •Your healthcare provider will tell you how much levetiracetam extended-release tablets to take and when to take it. Levetiracetam extended-release tablet is usually taken once a day. Take levetiracetam extended-release tablets at the same time each day.
• •Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.
• •Take levetiracetam extended-release tablets with or without food.
• •Swallow the tablets whole. Do not chew, break, or crush tablets.
• •If you miss a dose of levetiracetam extended-release tablets, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take two doses at the same time.
• •Patients receiving levetiracetam extended-release tablets may notice an inert matrix tablet passing in the stool. Patients should be informed that the active medication has already been absorbed by the time the patient sees the inert matrix tablet.
• •If you take too much levetiracetam extended-release tablets, call your local Poison Control Center or go to the nearest emergency room right away.

What should I avoid while taking levetiracetam extended-release tablets?

Do not drive, operate machinery or do other dangerous activities until you know how levetiracetam extended-release tablets affect you. Levetiracetam extended-release tablets may make you dizzy or sleepy.

What are the possible side effects of levetiracetam extended-release tablets?

•  See "What is the most important information I should know about levetiracetam extended-release tablets?"

Levetiracetam extended-release tablets can cause serious side effects.

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

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

•  extreme sleepiness, tiredness, and weakness

•  problems with muscle coordination (problems walking and moving)

Common side effects seen in people who take levetiracetam extended-release tablets and other formulations of levetiracetam include:

•  sleepiness

•  weakness

•  dizziness

•  infection

These side effects can happen at any time but happen more often within the first 4 weeks of treatment except for infection.

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

These are not all the possible side effects of levetiracetam extended-release tablets. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may also report side effects to FDA at 1-800-FDA-1088.

You may also report side effects to Lupin Pharmaceuticals, Inc. at 1-800-399-2561.

How should I store levetiracetam extended-release tablets?

• •Store levetiracetam extended-release tablets at room temperature, 59° to 86°F (15°C to 30°C) away from heat and light.
• • Keep levetiracetam extended-release tablets and all medicines out of the reach of children.

General information about levetiracetam extended-release tablets

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

This Medication Guide summarizes the most important information about levetiracetam extended-release tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about levetiracetam extended-release tablets that is written for health professionals.

What are the ingredients of levetiracetam extended-release tablets?

Levetiracetam extended-release tablets contain the labeled amount of levetiracetam. Inactive ingredients: colloidal silicon dioxide, dibasic calcium phosphate anhydrous, hydrogenated vegetable oil, hypromellose, lactose anhydrous, magnesium stearate, polyvinyl alcohol, polyethylene glycol, talc and titanium dioxide. The imprinting ink contains shellac, iron oxide black and propylene glycol.

Levetiracetam extended-release tablet does not contain gluten.

Manufactured By:

Lupin Limited

Goa 403 722 India

For BluePoint Laboratories

Rev 06/14

Package/Label Display Panel

Levetiracetam Extended Release Tablets USP

NDC: 68001-113-06, 60 Tablets