These Highlights Do Not Include All The Information Needed To Use Elepsia Xr Safely And Effectively. See Full Prescribing Information For Elepsia Xr.

Behavioral Abnormalities

ELEPSIA XR contains levetiracetam, an antiepileptic drug, as extended-release tablets for oral administration.

The chemical name of levetiracetam, a single enantiomer, is (-)-(S)-α-ethyl-2-oxo-1-pyrrolidine acetamide, its molecular formula is C₈H₁₄N₂O₂ and its molecular weight is 170.21. Levetiracetam is chemically unrelated to existing antiepileptic drugs (AEDs). It has the following structural formula:

Levetiracetam, USP is a white to off-white crystalline powder with a faint odor and a bitter taste. It is very soluble in water (104 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.

Each extended-release tablet contains 1000 mg or 1500 mg of levetiracetam. Inactive ingredients: amino methacrylate copolymer, colloidal silicon dioxide, crospovidone, dibutyl sebacate, ethyl cellulose, FD&C Blue #1 aluminum lake, hypromellose, magnesium stearate, polyethylene glycol, polysorbate 20, polysorbate 80, polyvinyl alcohol, povidone, silicified microcrystalline cellulose, sodium lauryl sulfate, talc, and triethyl citrate. The imprinting ink contains ammonium hydroxide, iron oxide black, N-butyl alcohol, propylene glycol, and shellac glaze.

ELEPSIA XR is a bilayer coated tablet. The medication is present in core of tablet and release controlling polymers are present in core and coating of tablet. The biologically inert components of core tablet and/or coating may occasionally remain intact during GI transit and may be eliminated in feces as inert fragments of coating and/or soft, hydrated mass.

ELEPSIA™ XR (e lep' see a ex are)

(levetiracetam)

extended-release tablets, for oral use

Read this Medication Guide before you start taking ELEPSIA XR and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about ELEPSIA XR?

Like other antiepileptic drugs, ELEPSIA XR 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 ELEPSIA XR without first talking to a healthcare provider.

• Stopping ELEPSIA XR 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 is ELEPSIA XR?

ELEPSIA XR is a prescription medicine taken by mouth that is used with other medicines to treat partial onset seizures in people 12 years of age and older.

It is not known if ELEPSIA XR is safe or effective in people under 12 years of age.

Who should not take ELEPSIA XR?

Do not take ELEPSIA XR if you are allergic to levetiracetam.

What should I tell my healthcare provider before starting ELEPSIA XR?

Before taking ELEPSIA XR, 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 ELEPSIA XR will harm your unborn baby. You and your healthcare provider will have to decide if you should take ELEPSIA XR while you are pregnant. If you become pregnant while taking ELEPSIA XR, 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 or go to http://www.aedpregnancyregistry.org. The purpose of this registry is to collect information about the safety of ELEPSIA XR and other antiepileptic medicines during pregnancy.
• are breastfeeding or plan to breastfeed. ELEPSIA XR can pass into your breast milk. It is not known if the ELEPSIA XR that passes into your breast milk can harm your baby. Talk to your healthcare provider about the best way to feed your baby while you receive ELEPSIA XR.

Tell your healthcare provider about all the medicines you take, including prescription and over -the-counter 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 ELEPSIA XR?

Take ELEPSIA XR exactly as your healthcare provider tells you take it.

• Your healthcare provider will tell you how much ELEPSIA XR to take and when to take it. ELEPSIA XR is usually taken 1 time per day.
• Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.
• Swallow the tablets whole. Do not chew, cut, break, split or crush tablets.
• Each coated tablet has 2 layers, a blue layer and a white to off-white layer. If you do not see the blue or white off- white layer, do not take the tablet and talk to your pharmacist.
• The inactive part of ELEPSIA XR tablets may not dissolve after all the medicine has been released in your body. You may sometimes notice something in your bowel movement that looks like pieces of coating or swollen pieces of the original tablet. This is normal.
• If you take too much ELEPSIA XR, call your local Poison Control Center or go to the nearest emergency room right away.

What should I avoid while taking ELEPSIA XR?

Do not drive, operate machinery or do other dangerous activities until you know how ELEPSIA XR affects you. ELEPSIA XR may make you dizzy or sleepy.

What are the possible side effects of ELEPSIA XR?

See "What is the most important information I should know about ELEPSIA XR?"

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)
• allergic reactions such as swelling of the face, lips, eyes, tongue, and throat, trouble swallowing or breathing, and hives.
• a skin rash. Serious skin rashes can happen after you start taking ELEPSIA XR. There is no way to tell if a mild rash will become a serious reaction.
• a serious allergic reaction that may affect your skin or other parts of your body such as your liver, kidneys, heart, or blood cells. This allergic reaction can be life-threatening and can cause death, particularly if it is not treated as early as possible. Call your healthcare provider right away if you have:
  • a skin rash
  • fever or swollen glands that do not go away
  • swelling of your face
  • shortness of breath
  • yellowing of the skin or whites of the eyes
  • dark urine

Common side effects seen in people who take ELEPSIA XR:

• flu
• sleepiness
• irritability
• nasal congestion, sore throat, and runny nose (nasopharyngitis)
• dizziness
• nausea

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 ELEPSIA XR. For more information, ask your healthcare provider or pharmacist.

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

How should I store ELEPSIA XR?

Store ELEPSIA XR at room temperature, between 68°F to 77°F (20°C to 25°C) away from light.

Keep ELEPSIA XR and all medicines out of the reach of children.

General information about the safe and effective use of ELEPSIA XR.

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

You can ask your pharmacist or healthcare provider for information about ELEPSIA XR that is written for health professionals.

What are the ingredients of ELEPSIA XR?

Active ingredient: levetiracetam

Inactive ingredients: amino methyacrylate copolymer, colloidal silicon dioxide, crospovidone, dibutyl sebacate, ethyl cellulose, FD&C Blue #1 aluminum lake, hypromellose, magnesium stearate, polyethylene glycol, polysorbate 20, polysorbate 80, polyvinyl alcohol, povidone, silicified microcrystalline cellulose, sodium lauryl sulfate, talc, and triethyl citrate. The imprinting ink contains ammonium hydroxide, iron oxide black, N-butyl alcohol, propylene glycol, and shellac glaze.

Rx Only

Manufactured by

Sun Pharmaceutical Industries Ltd.

Halol-Baroda Highway,

Halol-389 350, Gujarat, India

Manufactured for

Tripoint Therapeutics, LLC

Westfield, New Jersey

07090

Copyright 2020, Tripoint Therapeutics LLC

All rights reserved

For more information, call Tripoint Therapeutics at (908) 928-4500.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: 03/2024

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

ELEPSIA XR tablets, 1000 mg are oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on the blue layer; imprinted with "574" with black ink on one side and plain on the other side. They are supplied as follows:

ELEPSIA XR tablets, 1500 mg are oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on the blue layer; imprinted with "575" with black ink on one side and plain on the other side. They are supplied as follows:

Safety and effectiveness of ELEPSIA XR in pediatric patients 12 years of age and older has been established based on pharmacokinetic data in adults and adolescents using levetiracetam extended-release tablets and efficacy and safety data in controlled pediatric studies using immediate-release levetiracetam tablets [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1)].

Safety and effectiveness in pediatric patients below the age of 12 years have not been established.

A 3-month, randomized, double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of immediate-release levetiracetam tablets as adjunctive therapy in 98 pediatric patients with inadequately controlled partial seizures, ages 4 to 16 years (levetiracetam N=64; placebo N=34). The target dose of immediate-release levetiracetam tablets was 60 mg/kg/day. Neurocognitive effects were measured by the Leiter-R Attention and Memory (AM) Battery, which assesses various aspects of a child's memory and attention. Although no substantive differences were observed between the placebo-and levetiracetam-treated groups in the median change from baseline in this battery, the study was not adequate to assess formal statistical non-inferiority between the drug and placebo. The Achenbach Child Behavior Checklist (CBCL/6-18), a standardized validated tool used to assess a child's competencies and behavioral/emotional problems, was also assessed in this study. An analysis of the CBCL/6-18 indicated a worsening in aggressive behavior, one of the eight syndrome scores, in patients treated with levetiracetam [see Warnings and Precautions (5.1)].

There were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of levetiracetam extended-release tablets in these patients. It is expected that the safety of ELEPSIA XR in elderly patients 65 and over would be comparable to the safety observed in clinical studies of immediate-release levetiracetam tablets.

There were 347 subjects in clinical studies of immediate-release levetiracetam that were 65 and over. No overall differences in safety were observed between these subjects and younger subjects. There were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of immediate-release levetiracetam tablets in these patients.

Levetiracetam is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Clinical Pharmacology (12.3)].

The efficacy of ELEPSIA XR is based upon bioavailability studies comparing levetiracetam extended-release tablets to ELEPSIA XR extended-release tablets [see Clinical Pharmacology (12.3)] and the clinical studies described below using immediate-release and extended-release levetiracetam tablets.

The effectiveness of levetiracetam extended-release tablets as adjunctive therapy in partial-onset seizures in adults was established in one multicenter, randomized, double-blind, placebo-controlled clinical study in patients who had refractory partial-onset seizures with or without secondary generalization. This was supported by the demonstration of efficacy of immediate-release levetiracetam tablets (see below) in partial seizures in three multicenter, randomized, double-blind, placebo-controlled clinical studies in adults, as well as a demonstration of comparable bioavailability between the extended-release and immediate-release formulations [see Clinical Pharmacology (12.3)] in adults. The effectiveness for levetiracetam extended-release tablets as adjunctive therapy in partial-onset seizures in pediatric patients, 12 years of age and older, was based upon a single pharmacokinetic study showing comparable pharmacokinetics of levetiracetam extended-release tablets in adults and adolescents [see Clinical Pharmacology (12.3)]. All studies are described below.

ELEPSIA XR is contraindicated in patients with a hypersensitivity to levetiracetam. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.4)].

The following serious adverse reactions are discussed in more detail in other sections of labeling:

• Behavioral Abnormalities and Psychotic Symptoms [see Warnings and Precautions (5.1)]
• Suicidal Behavior and Ideation [see Warnings and Precautions (5.2)]
• Somnolence and Fatigue [see Warnings and Precautions (5.3)]
• Anaphylaxis and Angioedema [see Warnings and Precautions (5.4)]
• Serious Dermatological Reactions [see Warnings and Precautions (5.5)]
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.6)]
• Coordination Difficulties [see Warnings and Precautions (5.7)]
• Hematologic Abnormalities [see Warnings and Precautions (5.9)]

Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance [see Clinical Pharmacology (12.3)]. Dose adjustment is recommended for patients with mild renal impairment [see Dosage and Administration (2.2) ]. ELEPSIA XR is not recommended in patients with moderate or severe renal impairment. In patients with moderate or severe renal impairment, it is recommended that lower strength levetiracetam tablets be used instead of ELEPSIA XR.

In patients with end stage renal disease on dialysis, it is recommended that immediate-release levetiracetam tablets be used instead of ELEPSIA XR.

ELEPSIA XR is administered orally once daily.

Initiate treatment with a dose of 1000 mg once daily. The once daily dosage may be adjusted in increments of 1000 mg every 2 weeks, to a maximum recommended daily dose of 3000 mg/day.

ELEPSIA XR should be taken whole; do not split or cut tablets.

ELEPSIA XR is indicated as adjunctive therapy for the treatment of partial-onset seizures in patients 12 years of age and older.

As with most antiepileptic drugs, ELEPSIA XR should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus [see Dosage and Administration (2.3)]. But if withdrawal is needed because of an adverse event, rapid discontinuation can be considered.

The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown.

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.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Dispense in tight, light-resistant container.

• Behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability, and aggressive behavior have been observed; monitor patients for psychiatric signs and symptoms (5.1)
• Suicidal Behavior and Ideation: Monitor patients for new or worsening depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior (5.2)
• Monitor for somnolence and fatigue and advise patients not to drive or operate machinery until they have gained sufficient experience on ELEPSIA XR (5.3)
• Serious Dermatological Reactions: Discontinue ELEPSIA XR at the first sign of rash unless clearly not drug related (5.5)
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity: Discontinue if no alternative etiology (5.6)
• Coordination Difficulties: Monitor for ataxia, abnormal gait, and incoordination. Advise patients to not drive or operate machinery until they have gained experience on ELEPSIA XR (5.7)
• Withdrawal Seizures: ELEPSIA XR must be gradually withdrawn (5.8)

ELEPSIA XR may cause somnolence and fatigue. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on ELEPSIA XR to gauge whether it adversely affects their ability to drive or operate machinery.

There is no specific antidote for overdose with ELEPSIA XR. If indicated, elimination of unabsorbed drug should be attempted by emesis or gastric lavage; usual precautions should be observed to maintain airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the patient's clinical status. A Certified Poison Control Center should be contacted for up to date information on the management of overdose with ELEPSIA XR.

• Initiate treatment with a dose of 1000 mg once daily; increase by 1000 mg every 2 weeks to a maximum recommended dose of 3000 mg once daily (2.1)
• ELEPSIA XR should be taken whole; do not split or cut tablets (2.1)
• Not recommended for use in patients with moderate or severe renal impairment; the maximum recommended dose in patients with mild renal impairment is 2000 mg (2.2)

Extended-release tablets:

• 1000 mg: oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on blue layer; imprinted with "574" with black ink on one side and plain on the other side.
• 1500 mg: oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on blue layer; imprinted with "575" with black ink on one side and plain on the other side.

The following adverse reactions have been identified during postapproval use of immediate-release levetiracetam tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The listing is alphabetized: abnormal liver function test, acute kidney injury, anaphylaxis, angioedema, agranulocytosis, choreoathetosis, drug reaction with eosinophilia and systemic symptoms (DRESS), dyskinesia, erythema multiforme, hepatic failure, hepatitis, hyponatremia, muscular weakness, pancreatitis, pancytopenia (with bone marrow suppression identified in some of these cases), panic attack, thrombocytopenia, weight loss, and worsening of seizures. Alopecia has been reported with immediate-release levetiracetam tablet use; recovery was observed in majority of cases where immediate-release levetiracetam tablets were discontinued.

Coordination difficulties were not observed in the extended-release levetiracetam controlled trials, however, the number of patients exposed to levetiracetam extended-release tablets was considerably smaller than the number of patients exposed to immediate-release levetiracetam tablets in controlled trials. However, adverse reactions observed in the immediate-release levetiracetam controlled trials may also occur in patients receiving ELEPSIA XR.

ELEPSIA XR can cause hematologic abnormalities. Hematologic abnormalities occurred in clinical trials of immediate- release levetiracetam and included decreases in white blood cells (WBC), neutrophil, and red blood cell (RBC) counts; decreases in hemoglobin and hematocrit; and increases in eosinophil counts. Cases of agranulocytosis, pancytopenia, and thrombocytopenia have also been reported in the postmarketing setting. A complete blood count is recommended in patients experiencing significant weakness, pyrexia, recurrent infections, or coagulation disorders.

Pregnancy: Plasma levels of levetiracetam may be decreased and therefore need to be monitored closely during pregnancy. Based on animal data, may cause fetal harm (5.10, 8.1)

ELEPSIA XR can cause anaphylaxis or angioedema after the first dose or at any time during treatment. Signs and symptoms in cases reported in the postmarketing setting in patients treated with levetiracetam have included hypotension, hives, rash, respiratory distress, and swelling of the face, lip, mouth, eye, tongue, throat, and feet. In some reported cases, reactions were life-threatening and required emergency treatment. If a patient develops signs or symptoms of anaphylaxis or angioedema, ELEPSIA XR should be discontinued and the patient should seek immediate medical attention. ELEPSIA XR should be discontinued permanently if a clear alternative etiology for the reaction cannot be established [see Contraindications (4)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Advise the patient to read the FDA-approved Patient Labeling (Medication Guide).

When discontinuing ELEPSIA XR, reduce the dosage gradually and avoid abrupt discontinuation because of the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.8)].

Antiepileptic drugs (AEDs), including ELEPSIA XR, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs.

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing ELEPSIA XR or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients 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. ELEPSIA XR 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.

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.

ELEPSIA XR may cause behavioral abnormalities and psychotic symptoms. Patients treated with ELEPSIA XR should be monitored for psychiatric signs and symptoms.

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 (Study 1).

NDC 80705-100-30

ELEPSIA™ XR

(levetiracetam)

Extended-release Tablets

1000 mg

Once Daily Dosing

PHARMACIST: Dispense with Medication

Guide to each patient.

Rx only

Tripoint

Therapeutics

30 tablets

NDC 80705-101-30

ELEPSIA™ XR

(levetiracetam)

Extended-release Tablets

1500 mg

Once Daily Dosing

PHARMACIST: Dispense with Medication

Guide to each patient.

Rx only

Tripoint

Therapeutics

30 tablets

The effectiveness of immediate-release levetiracetam as adjunctive therapy (added to other antiepileptic drugs) in adults was established in three multicenter, randomized, double-blind, placebo-controlled clinical studies in patients who had refractory partial-onset seizures with or without secondary generalization (Studies 2, 3, and 4). The tablet formulation was used in all three studies. In these studies, 904 patients were randomized to placebo, levetiracetam 1000 mg, levetiracetam 2000 mg, or levetiracetam 3000 mg/day. Patients enrolled in Study 2 or Study 3 had refractory partial-onset seizures for at least two years, and had taken two or more AEDs. Patients enrolled in Study 4 had refractory partial-onset seizures for at least 1 year and had taken one AED. At the time of the study, patients were taking a stable dose regimen of at least one AED, and could take a maximum of two AEDs. During the baseline period, patients had to have experienced at least two partial-onset seizures during each 4-week period.

ELEPSIA XR is not recommended for use in patients with moderate or severe renal impairment. Recommended doses and adjustment for patients with mild renal impairment are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this, an estimate of the patient's creatinine clearance (CL_cr) in mL/min must first be calculated using the following formula:

Then CL_cr is adjusted for body surface area (BSA) as follows:

The signs and symptoms for ELEPSIA XR overdose are expected to be similar to those seen with immediate-release levetiracetam tablets.

The highest known dose of oral immediate-release levetiracetam tablets received in the clinical development program was 6000 mg/day. Other than drowsiness, there were no adverse reactions in the few known cases of overdose in clinical trials. Cases of somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with immediate-release levetiracetam tablet overdoses in postmarketing use.

The use of levetiracetam extended-release tablets in pediatric patients 12 years of age and older is supported by Study 5, which was conducted using immediate-release levetiracetam. ELEPSIA XR is not indicated in pediatric patients below 12 years of age.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including levetiracetam. These events can be fatal or life-threatening, particularly if diagnosis and treatment do not occur as early as possible. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. ELEPSIA XR should be discontinued if an alternative etiology for the signs or symptoms cannot be established [see Contraindications (4)].

Behavioral Abnormalities

ELEPSIA XR contains levetiracetam, an antiepileptic drug, as extended-release tablets for oral administration.

The chemical name of levetiracetam, a single enantiomer, is (-)-(S)-α-ethyl-2-oxo-1-pyrrolidine acetamide, its molecular formula is C₈H₁₄N₂O₂ and its molecular weight is 170.21. Levetiracetam is chemically unrelated to existing antiepileptic drugs (AEDs). It has the following structural formula:

Levetiracetam, USP is a white to off-white crystalline powder with a faint odor and a bitter taste. It is very soluble in water (104 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.

Each extended-release tablet contains 1000 mg or 1500 mg of levetiracetam. Inactive ingredients: amino methacrylate copolymer, colloidal silicon dioxide, crospovidone, dibutyl sebacate, ethyl cellulose, FD&C Blue #1 aluminum lake, hypromellose, magnesium stearate, polyethylene glycol, polysorbate 20, polysorbate 80, polyvinyl alcohol, povidone, silicified microcrystalline cellulose, sodium lauryl sulfate, talc, and triethyl citrate. The imprinting ink contains ammonium hydroxide, iron oxide black, N-butyl alcohol, propylene glycol, and shellac glaze.

ELEPSIA XR is a bilayer coated tablet. The medication is present in core of tablet and release controlling polymers are present in core and coating of tablet. The biologically inert components of core tablet and/or coating may occasionally remain intact during GI transit and may be eliminated in feces as inert fragments of coating and/or soft, hydrated mass.

ELEPSIA™ XR (e lep' see a ex are)

(levetiracetam)

extended-release tablets, for oral use

Read this Medication Guide before you start taking ELEPSIA XR and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about ELEPSIA XR?

Like other antiepileptic drugs, ELEPSIA XR 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 ELEPSIA XR without first talking to a healthcare provider.

• Stopping ELEPSIA XR 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 is ELEPSIA XR?

ELEPSIA XR is a prescription medicine taken by mouth that is used with other medicines to treat partial onset seizures in people 12 years of age and older.

It is not known if ELEPSIA XR is safe or effective in people under 12 years of age.

Who should not take ELEPSIA XR?

Do not take ELEPSIA XR if you are allergic to levetiracetam.

What should I tell my healthcare provider before starting ELEPSIA XR?

Before taking ELEPSIA XR, 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 ELEPSIA XR will harm your unborn baby. You and your healthcare provider will have to decide if you should take ELEPSIA XR while you are pregnant. If you become pregnant while taking ELEPSIA XR, 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 or go to http://www.aedpregnancyregistry.org. The purpose of this registry is to collect information about the safety of ELEPSIA XR and other antiepileptic medicines during pregnancy.
• are breastfeeding or plan to breastfeed. ELEPSIA XR can pass into your breast milk. It is not known if the ELEPSIA XR that passes into your breast milk can harm your baby. Talk to your healthcare provider about the best way to feed your baby while you receive ELEPSIA XR.

Tell your healthcare provider about all the medicines you take, including prescription and over -the-counter 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 ELEPSIA XR?

Take ELEPSIA XR exactly as your healthcare provider tells you take it.

• Your healthcare provider will tell you how much ELEPSIA XR to take and when to take it. ELEPSIA XR is usually taken 1 time per day.
• Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.
• Swallow the tablets whole. Do not chew, cut, break, split or crush tablets.
• Each coated tablet has 2 layers, a blue layer and a white to off-white layer. If you do not see the blue or white off- white layer, do not take the tablet and talk to your pharmacist.
• The inactive part of ELEPSIA XR tablets may not dissolve after all the medicine has been released in your body. You may sometimes notice something in your bowel movement that looks like pieces of coating or swollen pieces of the original tablet. This is normal.
• If you take too much ELEPSIA XR, call your local Poison Control Center or go to the nearest emergency room right away.

What should I avoid while taking ELEPSIA XR?

Do not drive, operate machinery or do other dangerous activities until you know how ELEPSIA XR affects you. ELEPSIA XR may make you dizzy or sleepy.

What are the possible side effects of ELEPSIA XR?

See "What is the most important information I should know about ELEPSIA XR?"

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)
• allergic reactions such as swelling of the face, lips, eyes, tongue, and throat, trouble swallowing or breathing, and hives.
• a skin rash. Serious skin rashes can happen after you start taking ELEPSIA XR. There is no way to tell if a mild rash will become a serious reaction.
• a serious allergic reaction that may affect your skin or other parts of your body such as your liver, kidneys, heart, or blood cells. This allergic reaction can be life-threatening and can cause death, particularly if it is not treated as early as possible. Call your healthcare provider right away if you have:
  • a skin rash
  • fever or swollen glands that do not go away
  • swelling of your face
  • shortness of breath
  • yellowing of the skin or whites of the eyes
  • dark urine

Common side effects seen in people who take ELEPSIA XR:

• flu
• sleepiness
• irritability
• nasal congestion, sore throat, and runny nose (nasopharyngitis)
• dizziness
• nausea

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 ELEPSIA XR. For more information, ask your healthcare provider or pharmacist.

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

How should I store ELEPSIA XR?

Store ELEPSIA XR at room temperature, between 68°F to 77°F (20°C to 25°C) away from light.

Keep ELEPSIA XR and all medicines out of the reach of children.

General information about the safe and effective use of ELEPSIA XR.

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

You can ask your pharmacist or healthcare provider for information about ELEPSIA XR that is written for health professionals.

What are the ingredients of ELEPSIA XR?

Active ingredient: levetiracetam

Inactive ingredients: amino methyacrylate copolymer, colloidal silicon dioxide, crospovidone, dibutyl sebacate, ethyl cellulose, FD&C Blue #1 aluminum lake, hypromellose, magnesium stearate, polyethylene glycol, polysorbate 20, polysorbate 80, polyvinyl alcohol, povidone, silicified microcrystalline cellulose, sodium lauryl sulfate, talc, and triethyl citrate. The imprinting ink contains ammonium hydroxide, iron oxide black, N-butyl alcohol, propylene glycol, and shellac glaze.

Rx Only

Manufactured by

Sun Pharmaceutical Industries Ltd.

Halol-Baroda Highway,

Halol-389 350, Gujarat, India

Manufactured for

Tripoint Therapeutics, LLC

Westfield, New Jersey

07090

Copyright 2020, Tripoint Therapeutics LLC

All rights reserved

For more information, call Tripoint Therapeutics at (908) 928-4500.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: 03/2024

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

ELEPSIA XR tablets, 1000 mg are oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on the blue layer; imprinted with "574" with black ink on one side and plain on the other side. They are supplied as follows:

ELEPSIA XR tablets, 1500 mg are oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on the blue layer; imprinted with "575" with black ink on one side and plain on the other side. They are supplied as follows:

Safety and effectiveness of ELEPSIA XR in pediatric patients 12 years of age and older has been established based on pharmacokinetic data in adults and adolescents using levetiracetam extended-release tablets and efficacy and safety data in controlled pediatric studies using immediate-release levetiracetam tablets [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1)].

Safety and effectiveness in pediatric patients below the age of 12 years have not been established.

A 3-month, randomized, double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of immediate-release levetiracetam tablets as adjunctive therapy in 98 pediatric patients with inadequately controlled partial seizures, ages 4 to 16 years (levetiracetam N=64; placebo N=34). The target dose of immediate-release levetiracetam tablets was 60 mg/kg/day. Neurocognitive effects were measured by the Leiter-R Attention and Memory (AM) Battery, which assesses various aspects of a child's memory and attention. Although no substantive differences were observed between the placebo-and levetiracetam-treated groups in the median change from baseline in this battery, the study was not adequate to assess formal statistical non-inferiority between the drug and placebo. The Achenbach Child Behavior Checklist (CBCL/6-18), a standardized validated tool used to assess a child's competencies and behavioral/emotional problems, was also assessed in this study. An analysis of the CBCL/6-18 indicated a worsening in aggressive behavior, one of the eight syndrome scores, in patients treated with levetiracetam [see Warnings and Precautions (5.1)].

There were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of levetiracetam extended-release tablets in these patients. It is expected that the safety of ELEPSIA XR in elderly patients 65 and over would be comparable to the safety observed in clinical studies of immediate-release levetiracetam tablets.

There were 347 subjects in clinical studies of immediate-release levetiracetam that were 65 and over. No overall differences in safety were observed between these subjects and younger subjects. There were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of immediate-release levetiracetam tablets in these patients.

Levetiracetam is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Clinical Pharmacology (12.3)].

The efficacy of ELEPSIA XR is based upon bioavailability studies comparing levetiracetam extended-release tablets to ELEPSIA XR extended-release tablets [see Clinical Pharmacology (12.3)] and the clinical studies described below using immediate-release and extended-release levetiracetam tablets.

The effectiveness of levetiracetam extended-release tablets as adjunctive therapy in partial-onset seizures in adults was established in one multicenter, randomized, double-blind, placebo-controlled clinical study in patients who had refractory partial-onset seizures with or without secondary generalization. This was supported by the demonstration of efficacy of immediate-release levetiracetam tablets (see below) in partial seizures in three multicenter, randomized, double-blind, placebo-controlled clinical studies in adults, as well as a demonstration of comparable bioavailability between the extended-release and immediate-release formulations [see Clinical Pharmacology (12.3)] in adults. The effectiveness for levetiracetam extended-release tablets as adjunctive therapy in partial-onset seizures in pediatric patients, 12 years of age and older, was based upon a single pharmacokinetic study showing comparable pharmacokinetics of levetiracetam extended-release tablets in adults and adolescents [see Clinical Pharmacology (12.3)]. All studies are described below.

ELEPSIA XR is contraindicated in patients with a hypersensitivity to levetiracetam. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.4)].

The following serious adverse reactions are discussed in more detail in other sections of labeling:

• Behavioral Abnormalities and Psychotic Symptoms [see Warnings and Precautions (5.1)]
• Suicidal Behavior and Ideation [see Warnings and Precautions (5.2)]
• Somnolence and Fatigue [see Warnings and Precautions (5.3)]
• Anaphylaxis and Angioedema [see Warnings and Precautions (5.4)]
• Serious Dermatological Reactions [see Warnings and Precautions (5.5)]
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.6)]
• Coordination Difficulties [see Warnings and Precautions (5.7)]
• Hematologic Abnormalities [see Warnings and Precautions (5.9)]

Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance [see Clinical Pharmacology (12.3)]. Dose adjustment is recommended for patients with mild renal impairment [see Dosage and Administration (2.2) ]. ELEPSIA XR is not recommended in patients with moderate or severe renal impairment. In patients with moderate or severe renal impairment, it is recommended that lower strength levetiracetam tablets be used instead of ELEPSIA XR.

In patients with end stage renal disease on dialysis, it is recommended that immediate-release levetiracetam tablets be used instead of ELEPSIA XR.

ELEPSIA XR is administered orally once daily.

Initiate treatment with a dose of 1000 mg once daily. The once daily dosage may be adjusted in increments of 1000 mg every 2 weeks, to a maximum recommended daily dose of 3000 mg/day.

ELEPSIA XR should be taken whole; do not split or cut tablets.

ELEPSIA XR is indicated as adjunctive therapy for the treatment of partial-onset seizures in patients 12 years of age and older.

As with most antiepileptic drugs, ELEPSIA XR should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus [see Dosage and Administration (2.3)]. But if withdrawal is needed because of an adverse event, rapid discontinuation can be considered.

The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown.

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.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Dispense in tight, light-resistant container.

• Behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability, and aggressive behavior have been observed; monitor patients for psychiatric signs and symptoms (5.1)
• Suicidal Behavior and Ideation: Monitor patients for new or worsening depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior (5.2)
• Monitor for somnolence and fatigue and advise patients not to drive or operate machinery until they have gained sufficient experience on ELEPSIA XR (5.3)
• Serious Dermatological Reactions: Discontinue ELEPSIA XR at the first sign of rash unless clearly not drug related (5.5)
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity: Discontinue if no alternative etiology (5.6)
• Coordination Difficulties: Monitor for ataxia, abnormal gait, and incoordination. Advise patients to not drive or operate machinery until they have gained experience on ELEPSIA XR (5.7)
• Withdrawal Seizures: ELEPSIA XR must be gradually withdrawn (5.8)

ELEPSIA XR may cause somnolence and fatigue. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on ELEPSIA XR to gauge whether it adversely affects their ability to drive or operate machinery.

There is no specific antidote for overdose with ELEPSIA XR. If indicated, elimination of unabsorbed drug should be attempted by emesis or gastric lavage; usual precautions should be observed to maintain airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the patient's clinical status. A Certified Poison Control Center should be contacted for up to date information on the management of overdose with ELEPSIA XR.

• Initiate treatment with a dose of 1000 mg once daily; increase by 1000 mg every 2 weeks to a maximum recommended dose of 3000 mg once daily (2.1)
• ELEPSIA XR should be taken whole; do not split or cut tablets (2.1)
• Not recommended for use in patients with moderate or severe renal impairment; the maximum recommended dose in patients with mild renal impairment is 2000 mg (2.2)

Extended-release tablets:

• 1000 mg: oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on blue layer; imprinted with "574" with black ink on one side and plain on the other side.
• 1500 mg: oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on blue layer; imprinted with "575" with black ink on one side and plain on the other side.

The following adverse reactions have been identified during postapproval use of immediate-release levetiracetam tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The listing is alphabetized: abnormal liver function test, acute kidney injury, anaphylaxis, angioedema, agranulocytosis, choreoathetosis, drug reaction with eosinophilia and systemic symptoms (DRESS), dyskinesia, erythema multiforme, hepatic failure, hepatitis, hyponatremia, muscular weakness, pancreatitis, pancytopenia (with bone marrow suppression identified in some of these cases), panic attack, thrombocytopenia, weight loss, and worsening of seizures. Alopecia has been reported with immediate-release levetiracetam tablet use; recovery was observed in majority of cases where immediate-release levetiracetam tablets were discontinued.

Coordination difficulties were not observed in the extended-release levetiracetam controlled trials, however, the number of patients exposed to levetiracetam extended-release tablets was considerably smaller than the number of patients exposed to immediate-release levetiracetam tablets in controlled trials. However, adverse reactions observed in the immediate-release levetiracetam controlled trials may also occur in patients receiving ELEPSIA XR.

ELEPSIA XR can cause hematologic abnormalities. Hematologic abnormalities occurred in clinical trials of immediate- release levetiracetam and included decreases in white blood cells (WBC), neutrophil, and red blood cell (RBC) counts; decreases in hemoglobin and hematocrit; and increases in eosinophil counts. Cases of agranulocytosis, pancytopenia, and thrombocytopenia have also been reported in the postmarketing setting. A complete blood count is recommended in patients experiencing significant weakness, pyrexia, recurrent infections, or coagulation disorders.

Pregnancy: Plasma levels of levetiracetam may be decreased and therefore need to be monitored closely during pregnancy. Based on animal data, may cause fetal harm (5.10, 8.1)

ELEPSIA XR can cause anaphylaxis or angioedema after the first dose or at any time during treatment. Signs and symptoms in cases reported in the postmarketing setting in patients treated with levetiracetam have included hypotension, hives, rash, respiratory distress, and swelling of the face, lip, mouth, eye, tongue, throat, and feet. In some reported cases, reactions were life-threatening and required emergency treatment. If a patient develops signs or symptoms of anaphylaxis or angioedema, ELEPSIA XR should be discontinued and the patient should seek immediate medical attention. ELEPSIA XR should be discontinued permanently if a clear alternative etiology for the reaction cannot be established [see Contraindications (4)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Advise the patient to read the FDA-approved Patient Labeling (Medication Guide).

When discontinuing ELEPSIA XR, reduce the dosage gradually and avoid abrupt discontinuation because of the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.8)].

Antiepileptic drugs (AEDs), including ELEPSIA XR, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs.

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing ELEPSIA XR or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients 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. ELEPSIA XR 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.

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.

ELEPSIA XR may cause behavioral abnormalities and psychotic symptoms. Patients treated with ELEPSIA XR should be monitored for psychiatric signs and symptoms.

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 (Study 1).

NDC 80705-100-30

ELEPSIA™ XR

(levetiracetam)

Extended-release Tablets

1000 mg

Once Daily Dosing

PHARMACIST: Dispense with Medication

Guide to each patient.

Rx only

Tripoint

Therapeutics

30 tablets

NDC 80705-101-30

ELEPSIA™ XR

(levetiracetam)

Extended-release Tablets

1500 mg

Once Daily Dosing

PHARMACIST: Dispense with Medication

Guide to each patient.

Rx only

Tripoint

Therapeutics

30 tablets

The effectiveness of immediate-release levetiracetam as adjunctive therapy (added to other antiepileptic drugs) in adults was established in three multicenter, randomized, double-blind, placebo-controlled clinical studies in patients who had refractory partial-onset seizures with or without secondary generalization (Studies 2, 3, and 4). The tablet formulation was used in all three studies. In these studies, 904 patients were randomized to placebo, levetiracetam 1000 mg, levetiracetam 2000 mg, or levetiracetam 3000 mg/day. Patients enrolled in Study 2 or Study 3 had refractory partial-onset seizures for at least two years, and had taken two or more AEDs. Patients enrolled in Study 4 had refractory partial-onset seizures for at least 1 year and had taken one AED. At the time of the study, patients were taking a stable dose regimen of at least one AED, and could take a maximum of two AEDs. During the baseline period, patients had to have experienced at least two partial-onset seizures during each 4-week period.

ELEPSIA XR is not recommended for use in patients with moderate or severe renal impairment. Recommended doses and adjustment for patients with mild renal impairment are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this, an estimate of the patient's creatinine clearance (CL_cr) in mL/min must first be calculated using the following formula:

Then CL_cr is adjusted for body surface area (BSA) as follows:

The signs and symptoms for ELEPSIA XR overdose are expected to be similar to those seen with immediate-release levetiracetam tablets.

The highest known dose of oral immediate-release levetiracetam tablets received in the clinical development program was 6000 mg/day. Other than drowsiness, there were no adverse reactions in the few known cases of overdose in clinical trials. Cases of somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with immediate-release levetiracetam tablet overdoses in postmarketing use.

The use of levetiracetam extended-release tablets in pediatric patients 12 years of age and older is supported by Study 5, which was conducted using immediate-release levetiracetam. ELEPSIA XR is not indicated in pediatric patients below 12 years of age.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including levetiracetam. These events can be fatal or life-threatening, particularly if diagnosis and treatment do not occur as early as possible. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. ELEPSIA XR should be discontinued if an alternative etiology for the signs or symptoms cannot be established [see Contraindications (4)].