Drug: Elepsia XR

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 1,000 mg or 1,500 mg of levetiracetam. Inactive ingredients: povidone, hypromellose, amino methacrylate copolymer, colloidal silicon dioxide, magnesium stearate, talc, silicified microcrystalline cellulose, crospovidone, sodium lauryl sulfate, FD&C Blue #1 aluminum lake, ethylcellulose, dibutyl sebacate, triethyl citrate, polysorbate 20, polyvinyl alcohol, polyethylene glycol, and polysorbate 80. The imprinting ink contains shellac glaze, iron oxide black, N-butyl alcohol, propylene glycol, and ammonium hydroxide. Last reviewed on RxList: 4/8/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

The following serious adverse reactions are discussed below and elsewhere in the labeling:
  • Psychiatric Reactions [see WARNINGS AND PRECAUTIONS]
  • Suicidal Behavior And Ideation [see WARNINGS AND PRECAUTIONS]
  • Somnolence And Fatigue [see WARNINGS AND PRECAUTIONS]
  • Serious Dermatological Reactions [see WARNINGS AND PRECAUTIONS]
  • Coordination Difficulties [see WARNINGS AND PRECAUTIONS]
  • Withdrawal Seizures [see WARNINGS AND PRECAUTIONS]
  • Hematologic Abnormalities [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience 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. The prescriber should be aware that the adverse reaction incidence figures in the following table, obtained when levetiracetam extended-release tablets were added to concurrent AED therapy, cannot be used to predict the frequency of adverse reactions in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical trials. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescriber with one basis to estimate the relative contribution of drug and non-drug factors to the adverse reaction incidences in the population studied. Levetiracetam Extended-Release Tablets In the controlled clinical study using levetiracetam extended-release tablets in patients with partial onset seizures (Study 1), the most frequently reported adverse reactions in patients receiving levetiracetam extended-release tablets in combination with other AEDs, for events with rates greater than placebo, were irritability and somnolence. Table 3 lists adverse reactions that occurred in at least 5% of epilepsy patients treated with levetiracetam extended-release tablets participating in the placebo-controlled study (Study 1) and were numerically more common than in patients treated with placebo. In this study, either levetiracetam extended-release tablets or placebo was added to concurrent AED therapy. Table 3: Incidence (%) Of Adverse Reactions In The Placebo-Controlled, Add-On Study By Body System (Adverse Reactions Occurred In At Least 5% Of Levetiracetam Extended-Release Tablets-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)
Body System/
Adverse Reaction Levetiracetam Extended-Release Tablets
(N=77) % Placebo
(N=79) % Gastrointestinal Disorders Nausea 5 3 Infections and Infestations Influenza 8 4 Nasopharyngitis 7 5 Nervous System Disorders Somnolence 8 3 Dizziness 5 3 Psychiatric Disorders Irritability 7 0 Discontinuation or Dose Reduction in the Levetiracetam Extended-Release Tablets Controlled Clinical Study In the controlled clinical study using levetiracetam extended-release tablets, 5.2% of patients receiving levetiracetam extended-release tablets and 2.5% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions that resulted in discontinuation and that occurred more frequently in levetiracetam extended-release tablets-treated patients than in placebo-treated patients were asthenia, epilepsy, mouth ulceration, rash and respiratory failure. Each of these adverse reactions led to discontinuation in a levetiracetam extended-release tablets-treated patient and no placebo-treated patients. Table 4 lists the adverse reactions seen in the controlled studies of immediate-release levetiracetam tablets in adult patients experiencing partial onset seizures. Although the pattern of adverse reactions in the levetiracetam extended-release tablets study seems somewhat different from that seen in partial onset seizure controlled studies for immediate-release levetiracetam tablets, this is possibly due to the much smaller number of patients in this study compared to the immediate-release tablet studies. The adverse reactions for levetiracetam extended-release tablets are expected to be similar to those seen with immediate-release levetiracetam tablets. Immediate-Release Levetiracetam Tablets Adults In controlled clinical studies of immediate-release levetiracetam tablets as adjunctive therapy to other AEDs in adults with partial onset seizures, the most frequently reported adverse reactions, for events with rates greater than placebo, were somnolence, asthenia, infection and dizziness. Table 4 lists adverse reactions that occurred in at least 1% of adult epilepsy patients treated with immediate-release levetiracetam tablets participating in placebo-controlled studies and were numerically more common than in patients treated with placebo. In these studies, either immediate-release levetiracetam tablets or placebo was added to concurrent AED therapy. Table 4: Incidence (%) Of Adverse Reactions In Placebo-Controlled, Add-On Studies In Adults Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 1% Of Immediate-Release Levetiracetam Tablets-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)
Body System/
Adverse Reaction Immediate-Release Levetiracetam Tablets
(N=769) % Placebo
(N=439) % Body as a Whole Asthenia 15 9 Headache 14 13 Infection 13 8 Pain 7 6 Digestive System Anorexia 3 2 Nervous System Somnolence 15 8 Dizziness 9 4 Depression 4 2 Nervousness 4 2 Ataxia 3 1 Vertigo 3 1 Amnesia 2 1 Anxiety 2 1 Hostility 2 1 Paresthesia 2 1 Emotional Lability 2 0 Respiratory System Pharyngitis 6 4 Rhinitis 4 3 Cough Increased 2 1 Sinusitis 2 1 Special Senses Diplopia 2 1 Pediatric Patients 4 Years to < 16 Years In a pooled analysis of two controlled pediatric clinical studies in children 4 to 16 years of age with partial onset seizures, the adverse reactions most frequently reported with the use of immediate-release levetiracetam tablets in combination with other AEDs, and with greater frequency than in patients on placebo, were fatigue, aggression, nasal congestion, decreased appetite, and irritability. Table 5 lists adverse reactions that occurred in at least 2% of pediatric patients treated with immediate-release levetiracetam tablets and were more common than in pediatric patients on placebo. In these studies, either immediate-release levetiracetam tablets or placebo was added to concurrent AED therapy. Table 5: Incidence (%) Of Adverse Reactions In Pooled Placebo-Controlled, Add-On Studies In Pediatric Patients Ages 4 to 16 Years Experiencing Partial Onset Seizures By Body System (Adverse Reactions Occurred In At Least 2% Of Patients Treated With Immediate-Release Levetiracetam Tablets And Occurred More Frequently Than Patients on Placebo)
Body System/
Adverse Reaction Immediate-Release Levetiracetam Tablets
(N=165) % Placebo
(N=131) % Ear and Labyrinth Disorders Ear Pain 2 1 Eye Disorders Conjunctivitis 2 0 Gastrointestinal Disorders Vomiting 15 12 Upper Abdominal Pain 9 8 Diarrhea 6 5 Constipation 3 1 General Disorders and Administration Site Conditions Fatigue 11 5 Infections and Infestations Nasopharyngitis 15 12 Influenza 3 1 Gastroenteritis 2 0 Rhinitis 2 0 Injury, Poisoning and Procedural Complications Head Injury 4 0 Contusion 3 1 Fall 3 2 Joint Sprain 2 1 Metabolism and Nutrition Disorders Decreased Appetite 8 2 Anorexia 4 3 Musculoskeletal and Connective Tissue Disorders Arthralgia 2 0 Neck Pain 2 1 Nervous System Headache 19 15 Somnolence 13 9 Dizziness 7 5 Lethargy 6 2 Sedation 2 1 Psychiatric Disorders Aggression 10 5 Abnormal Behavior 7 4 Irritability 7 1 Insomnia 5 3 Agitation 4 1 Depression 3 1 Altered Mood 3 1 Affect Lability 2 1 Anxiety 2 1 Confusional State 2 0 Mood Swings 2 1 Respiratory, Thoracic and Mediastinal Disorders Cough 9 5 Nasal Congestion 9 2 Pharyngolaryngeal Pain 7 4 In controlled pediatric clinical studies in patients 4 to 16 years of age, 7% of patients treated with immediate-release levetiracetam tablets and 9% of patients on placebo discontinued as a result of an adverse event. In addition, the following adverse reactions were seen in other well-controlled studies of immediate-release levetiracetam tablets: balance disorder, disturbance in attention, eczema, hyperkinesia, memory impairment, myalgia, personality disorders, pruritus, and vision blurred. Comparison of Gender, Age and Race There are insufficient data for levetiracetam extended-release tablets to support a statement regarding the distribution of adverse experience reports by gender, age and race. Read the Elepsia XR (levetiracetam extended-release tablets) Side Effects Center for a complete guide to possible side effectsLearn More »

Source: http://www.rxlist.com

Dosage Information ELEPSIA XR is administered once daily. Treatment should be initiated with a dose of 1,000 mg once daily. The once daily dosage may be adjusted in increments of 1,000 mg every 2 weeks to a maximum recommended once daily dose of 3,000 mg. ELEPSIA XR should be taken whole; do not split or cut tablets. Dosage In Patients With Renal Impairment ELEPSIA XR is not recommended for 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 (CLcr) in mL/min must first be calculated using the following formula: Males: (weight in kg) x (140 – age) (72) x serum creatinine (mg/100 mL) Females: (0.85) x (above value) Then CLcr is adjusted for body surface area (BSA) as follows: CLcr (mL/min/1.73m²) = CLcr (mL/min)/BSA subject (m²) x 1.73 Table 1: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function
Group Creatinine Clearance (mL/min/1.73m²) Dosage (mg) Frequency Normal greater than 80 1,000 to 3,000 Every 24 hours Mild 50 to 80 1,000 to 2,000 Every 24 hours

Source: http://www.rxlist.com

Postmarketing Experience In addition to the adverse reactions listed above for immediate-release levetiracetam tablets [see Clinical Trials Experience above], the following adverse reactions have been identified during post-approval 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, choreoathetosis, dyskinesia, erythema multiforme, hepatic failure, hepatitis, hyponatremia, leukopenia, muscular weakness, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression identified in some of these cases), panic attack, thrombocytopenia, and weight loss. Alopecia has been reported with immediate-release levetiracetam tablets use; recovery was observed in majority of cases where immediate-release levetiracetam tablets were discontinued. Last reviewed on RxList: 4/8/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

ELEPSIA XR is indicated as adjunctive therapy in the treatment of partial onset seizures in patients ≥ 12 years of age with epilepsy.

Source: http://www.rxlist.com

None. Last reviewed on RxList: 4/8/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Signs, Symptoms And Laboratory Findings Of Acute Overdosage In Humans The signs and symptoms for levetiracetam extended-release tablets 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 6,000 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 tablets overdoses in postmarketing use. Management Of Overdose There is no specific antidote for overdose with levetiracetam extended-release tablets. 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 levetiracetam extended-release tablets. Hemodialysis 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.

Source: http://www.rxlist.com

Dosage Forms And Strengths Extended-release tablets:
  • 1,000 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.
  • 1,500 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.
Storage And Handling Levetiracetam extended-release tablets, 1,000 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: Bottles of 30with child resistant cap…................... NDC 47133-574-83
Bottles of 100 with child resistant cap…................. NDC 47133-574-88
Bottles of 500 with non-child resistant cap………. NDC 47133-574-13 Levetiracetam extended-release tablets, 1,500 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: Bottles of 30 with child resistant cap…................... NDC 47133-575-83
Bottles of 100 with child resistant cap…................. NDC 47133-575-88
Bottles of 500 with non-child resistant cap………. NDC 47133-575-13 Storage 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. Distributed by: Sun Pharmaceutical Industries, Inc., Cranbury, NJ 08512. Manufactured by: Sun Pharmaceutical Ind. Ltd., Halol-Baroda Highway, Halol-389 350, Gujarat, India. Issued 03/2015 Last reviewed on RxList: 4/8/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Psychiatric Reactions Patients taking ELEPSIA XR should be monitored for behavioral abnormalities. Levetiracetam Extended-Release Tablets A total of 6.5% of patients treated with levetiracetam extended-release tablets experienced non-psychotic behavioral disorders (reported as irritability and aggression), compared to no patient on placebo. Irritability was reported in 6.5% of patients treated with levetiracetam extended-release tablets. Aggression was reported in 1.3% of patients treated with levetiracetam extended-release tablets. No patient discontinued treatment or had a dose reduction as a result of these adverse reactions. There is considerably less controlled clinical trial experience with levetiracetam extended-release tablets than with immediate-release levetiracetam tablets, and some adverse reactions observed with immediate-release levetiracetam tablets may not have been detected in levetiracetam extended-release tablets clinical trials because of limited number of patients. These adverse reactions may however occur in patients receiving ELEPSIA XR. Immediate-Release Levetiracetam Tablets A total of 13.3% of adult patients and 37.6% of pediatric patients (4 to 16 years of age) treated with immediate-release levetiracetam tablets experienced non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personality disorder), compared to 6.2% and 18.6% of adult and pediatric patients on placebo. A randomized, double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of immediate-release levetiracetam tablets as adjunctive therapy in pediatric patients (4 to 16 years of age). An exploratory analysis suggested a worsening in aggressive behavior in patients treated with immediate-release levetiracetam tablets in that study [see Use in Specific Populations]. A total of 1.7% of adult patients treated with immediate-release levetiracetam tablets discontinued treatment due to behavioral adverse events, compared to 0.2% of patients on placebo. The treatment dose was reduced in 0.8% of adult patients treated with immediate-release levetiracetam tablets, compared to 0.5% of patients on placebo. Overall, 10.9% of pediatric patients treated with immediate-release levetiracetam tablets experienced behavioral symptoms associated with discontinuation or dose reduction, compared to 6.2% of pediatric patients on placebo. One percent of adult patients and 2% of pediatric patients (4 to 16 years of age) treated with immediate-release levetiracetam tablets experienced psychotic symptoms, compared to 0.2% and 2%, respectively, in adult and pediatric patients on placebo. In the controlled study that assessed the neurocognitive and behavioral effects of immediate-release levetiracetam tablets in pediatric patients 4 to 16 years of age, 1 (1.6%) patient treated with levetiracetam experienced paranoia, compared to no patients on placebo. There were 2 (3.1%) patients treated with immediate-release levetiracetam tablets who experienced confusional state, compared to no patients on placebo [see Use in Specific Populations]. Two (0.3%) adult patients treated with immediate-release levetiracetam tablets were hospitalized, and their treatment was discontinued due to psychosis. In both patients, the psychosis event developed within the first week of treatment, and resolved within 1 to 2 weeks following treatment discontinuation. There was no difference between drug and placebo-treated patients in the incidence of pediatric patients who discontinued treatment due to psychotic and non-psychotic adverse reactions. Suicidal Behavior And Ideation 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. Table 2 : Risk By Indication For Antiepileptic Drugs In The Pooled Analysis
Indication Placebo Patients with Events Per 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1,000 Patients Epilepsy 1 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 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. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. Somnolence And Fatigue Patients should be monitored for somnolence and fatigue, and be advised not to drive or operate machinery until they have gained sufficient experience on levetiracetam extended-release tablets to gauge whether it adversely affects their ability to drive or operate machinery. In clinical trials of immediate-release levetiracetam tablets, somnolence and asthenia occurred most frequently within the first 4 weeks of treatment. Levetiracetam Extended-Release Tablets In the levetiracetam extended-release tablets double-blind, controlled trial in patients experiencing partial onset seizures, 7.8% of patients treated with levetiracetam extended-release tablets experienced somnolence compared to 2.5% of patients on placebo. No patient discontinued treatment or had a dose reduction as a result of these adverse reactions. There is considerably less controlled clinical trial experience with levetiracetam extended-release tablets than with immediate-release levetiracetam tablets, and some adverse reactions observed with immediate-release levetiracetam tablets may not have been detected in levetiracetam extended-release tablets clinical trials because of limited number of patients. These adverse reactions may however occur in patients receiving ELEPSIA XR. Immediate-Release Levetiracetam Tablets In general, the incidences of somnolence and fatigue in the pediatric partial onset seizure studies were comparable to those of the adult partial onset seizure studies. In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.8% of patients treated with immediate-release levetiracetam tablets reported somnolence, compared to 8.4% of patients on placebo. There was no clear dose response up to 3,000 mg/day. In a study in which there was no titration, about 45% of patients receiving 4,000 mg/day reported somnolence. The somnolence was considered serious in 0.3% of patients treated with immediate-release levetiracetam tablets, compared to no patients on placebo. About 3% of patients treated with immediate-release levetiracetam tablets discontinued treatment due to somnolence, compared to 0.7% of patients on placebo. The dose was reduced due to somnolence in 1.4% of patients treated with immediate-release levetiracetam tablets and in 0.9% of patients on placebo, while 0.3% of the patients treated with immediate-release levetiracetam tablets were hospitalized due to somnolence. In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.7% of patients treated with immediate-release levetiracetam tablets reported asthenia, compared to 9.1% of patients on placebo. Treatment was discontinued due to asthenia in 0.8% of patients treated with immediate-release levetiracetam tablets, compared to 0.5% of patients on placebo. The dose was reduced due to asthenia in 0.5% of patients treated with immediate-release levetiracetam tablets and in 0.2% of patients on placebo. Serious Dermatological Reactions Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in both children and adults treated with levetiracetam. The median time of onset is reported to be 14 to 17 days, but cases have been reported at least four months after initiation of treatment. Recurrence of the serious skin reactions following rechallenge with levetiracetam has also been reported. Levetiracetam extended-release tablets 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. Coordination Difficulties Patients should be monitored for coordination difficulties and advised not to drive or operate machinery until they have gained sufficient experience on levetiracetam extended-release tablets to gauge whether it could adversely affect their ability to drive or operate machinery. A total of 3.4% of adult patients treated with immediate-release levetiracetam tablets experienced coordination difficulties, (reported as either ataxia, abnormal gait, or incoordination), compared to 1.6% of patients on placebo. A total of 0.4% of patients in controlled trials discontinued immediate-release levetiracetam tablets treatment due to ataxia, compared to no patients on placebo. In 0.7% of patients treated with immediate-release levetiracetam tablets and in 0.2% of patients on placebo, the dose was reduced due to coordination difficulties, while one of the treated patients was hospitalized due to worsening of preexisting ataxia. These events occurred most frequently within the first 4 weeks of treatment. Coordination difficulties were not observed in the levetiracetam extended-release tablets controlled trial. There is considerably less controlled clinical trial experience with levetiracetam extended-release tablets than with immediate-release levetiracetam tablets, and some adverse reactions observed with immediate-release levetiracetam tablets may not have been detected in levetiracetam extended-release tablets clinical trials because of limited number of patients. These adverse reactions may however occur in patients receiving ELEPSIA XR. Withdrawal Seizures Antiepileptic drugs, including ELEPSIA XR, should be withdrawn gradually to minimize the potential of increased seizure frequency. Hematologic Abnormalities Although there were no obvious hematologic abnormalities observed in the levetiracetam extended-release tablets controlled study, there is considerably less controlled clinical trial experience with levetiracetam extended-release tablets than with immediate-release levetiracetam tablets, and some adverse reactions observed with immediate-release levetiracetam tablets may not have been detected in levetiracetam extended-release tablets clinical trials because of limited number of patients. These adverse reactions may however occur in patients receiving ELEPSIA XR. In controlled trials, a minor but statistically significant decrease (compared to placebo) in total mean RBC count (0.03 x 106/mm³), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%), was seen in adult patients treated with immediate-release levetiracetam tablets. A total of 3.2% of adult patients treated with immediate-release levetiracetam tablets, and 1.8% of patients on placebo had at least one possibly significant ( ≤ 2.8 x 109/L) decreased WBC, and 2.4% of patients treated with immediate-release levetiracetam tablets vs. 1.4% of patients on placebo had at least one possibly significant ( ≤ 1.0 x 109/L) decreased neutrophil count. Of the patients treated with immediate-release levetiracetam tablets with a low neutrophil count, all but one rose towards or to baseline with continued treatment. No patient was discontinued secondary to low neutrophil counts. In pediatric patients (4 to < 16 years of age), statistically significant decreases in WBC and neutrophil counts were seen in patients treated with immediate-release levetiracetam tablets, as compared to placebo. The mean decreases from baseline in the immediate-release levetiracetam tablets group were -0.4 × 109/L and -0.3 × 109/L, respectively, whereas there were small increases in the placebo group. A significant increase in mean relative lymphocyte counts was observed in 1.7% of patients treated with immediate-release levetiracetam tablets compared to a decrease of 4% in patients on placebo. In the controlled pediatric trial, a possibly clinically significant abnormal low WBC value was observed in 3% of patients treated with immediate-release levetiracetam tablets, compared to no patients on placebo. However, there was no apparent difference between treatment groups with respect to neutrophil count. No patient was discontinued secondary to low WBC or neutrophil counts. In the controlled pediatric cognitive and neuropsychological safety study, two subjects (6.1%) in the placebo group and 5 subjects (8.6%) in the immediate-release levetiracetam tablets-treated group had high eosinophil count values that were possibly clinically significant ( ≥ 10% or ≥ 0.7X109/L). Seizure Control During Pregnancy 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. Patient Counseling Information Advise the patient to read the FDA-approved Patient Labeling (Medication Guide). Suicidal Behavior and Ideation Counsel patients, their caregivers, and/or families that antiepileptic drugs (AEDs), including ELEPSIA XR, 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. Advise patients, their caregivers, and/or families to immediately report behaviors of concern to a healthcare provider [see WARNINGS AND PRECAUTIONS]. Psychiatric Reactions and Changes in Behavior Advise patients that ELEPSIA XR 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 [see WARNINGS AND PRECAUTIONS]. Effects on Driving or Operating Machinery Inform patients that ELEPSIA XR may cause dizziness and somnolence. Inform patients not to drive or operate machinery until they have gained sufficient experience on levetiracetam extended-release tablets to gauge whether it adversely affects their ability to drive or operate machinery [see WARNINGS AND PRECAUTIONS]. 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 [see WARNINGS AND PRECAUTIONS]. Dosage and Administration Instruct patients to only take ELEPSIA XR once daily and to swallow the tablets whole. The tablet should not be chewed, broken, split, or crushed [see DOSAGE AND ADMINISTRATION]. Each coated bilayer tablet consists of a distinctly visible blue layer and a white to off white layer. Do not consume the tablet if one layer is absent and report this to your pharmacist [see Dosage Forms and Strengths]. Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant while taking ELEPSIA XR. 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]. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis Rats were dosed with levetiracetam in the diet for 104 weeks at doses of 50, 300 and 1,800 mg/kg/day. The highest dose is 6 times the maximum recommended daily human dose (MRHD) of 3,000 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 4,000 mg/kg/day, lowered to 3,000 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 (3,000 mg/kg/day) is approximately 5 times the MRHD on a mg/m² basis. 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 1,800 mg/kg/day (6 times the maximum recommended human dose on a mg/m² or systemic exposure [AUC] basis). Use In Specific Populations Pregnancy ELEPSIA XR levels may decrease during pregnancy [see WARNINGS AND PRECAUTIONS]. Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. In animal studies, levetiracetam produced evidence of developmental toxicity, including teratogenic effects, at doses similar to or greater than human therapeutic doses. ELEPSIA XR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Oral administration of levetiracetam to female rats throughout pregnancy and lactation led to increased incidences of minor fetal skeletal abnormalities and retarded offspring growth pre-and/or postnatally at doses ≥ 350 mg/kg/day (equivalent to the maximum recommended human dose of 3,000 mg [MRHD] on a mg/m²basis) and with increased pup mortality and offspring behavioral alterations at a dose of 1,800 mg/kg/day (6 times the MRHD on a mg/m²basis). The developmental no effect dose was 70 mg/kg/day (0.2 times the MRHD on a mg/m²basis). There was no overt maternal toxicity at the doses used in this study. Oral administration of levetiracetam to pregnant rabbits during the period of organogenesis resulted in increased embryofetal mortality and increased incidences of minor fetal skeletal abnormalities at doses ≥ 600 mg/kg/day (4 times MRHD on a mg/m² basis) and in decreased fetal weights and increased incidences of fetal malformations at a dose of 1,800 mg/kg/day (12 times the MRHD on a mg/m² basis). The developmental no effect dose was 200 mg/kg/day (equivalent to the MRHD on a mg/m² basis). Maternal toxicity was also observed at 1,800 mg/kg/day. When levetiracetam was administered orally to pregnant rats during the period of organogenesis, fetal weights were decreased and the incidence of fetal skeletal variations was increased at a dose of 3,600 mg/kg/day (12 times the MRHD). 1,200 mg/kg/day (4 times the MRHD) was a developmental no effect dose. There was no evidence of maternal toxicity in this study. Treatment of rats with levetiracetam during the last third of gestation and throughout lactation produced no adverse developmental or maternal effects at oral doses of up to 1,800 mg/kg/day (6 times the MRHD on a mg/m² basis). Pregnancy Registry To provide information regarding the effects of in utero exposure to ELEPSIA XR, physicians are advised to recommend that pregnant patients taking ELEPSIA XR enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by the patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. Labor And Delivery The effect of ELEPSIA XR on labor and delivery in humans is unknown. Nursing Mothers Levetiracetam is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from levetiracetam extended-release tablets, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness 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, CLINICAL PHARMACOLOGY, and Clinical Studies]. Safety and effectiveness of levetiracetam extended-release tablets in 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]. Studies of levetiracetam in juvenile rats (dosing from day 4 through day 52 of age) and dogs (dosing from week 3 through week 7 of age) at doses of up to 1,800 mg/kg/day (approximately 7 and 24 times, respectively, the maximum recommended pediatric dose of 60 mg/kg/day on a mg/m² basis) did not indicate a potential for age-specific toxicity. Geriatric Use 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 levetiracetam extended-release tablets 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]. Renal Impairment The effect of levetiracetam extended-release tablets on renally impaired patients was not assessed in the controlled study. However, it is expected that the effect on ELEPSIA XR-treated patients would be similar to the effect seen in controlled studies of immediate-release levetiracetam tablets. Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance [see CLINICAL PHARMACOLOGY]. ELEPSIA XR is not recommended in patients with moderate or severe renal impairment. Dose adjustment is recommended for patients with mild renal impairment [see DOSAGE AND ADMINISTRATION]. Last reviewed on RxList: 4/8/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Health Services in

Drug Database Online

Welcome to Vaccine Health Center an online drug guide and dictionary, here you can get drug information and definitaions for most popular pharmaceutical and medicinal drugs, and specifically Elepsia XR. Find what medications you are taking today.