KEPPRA XR NDA 022285 S 020 FDA Approved Labeling Text Aug 2014 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use KEPPRA XR safely and effectively See full prescribing information for KEPPRA XR KEPPRA XR levetiracetam extended release tablets for oral use Initial U S Approval 1999 RECENT MAJOR CHANGES Indications and Usage 1 xx 2014 Warnings and Precautions 5 1 5 3 5 7 xx 2014 INDICATIONS AND USAGE KEPPRA XR is an antiepileptic drug indicated for adjunctive therapy in the treatment of partial onset seizures in patients 12 years of age with epilepsy 1 DOSAGE AND ADMINISTRATION KEPPRA XR is administered once daily treatment should be initiated with a dose of 1000 mg once daily the dosage may be adjusted in increments of 1000 mg every 2 weeks to a maximum recommended dose of 3000 mg once daily 2 1 KEPPRA XR dosing must be individualized according to renal function status 2 2 DOSAGE FORMS AND STRENGTHS 500 mg white film coated extended release tablet 3 750 mg white film coated extended release tablet 3 CONTRAINDICATIONS None 4 WARNINGS AND PRECAUTIONS Psychiatric Reactions Monitor patients for behavioral abnormalities including psychotic symptoms suicidal ideation irritability and aggressive behavior 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 Somnolence and Fatigue Monitor patients for these symptoms and advise patients not to drive or operate machinery until they have gained sufficient experience on KEPPRA XR 5 3 Withdrawal Seizures KEPPRA XR must be withdrawn gradually 5 6 ADVERSE REACTIONS Most common adverse reactions incidence in KEPPRA XR treated patients is 5 more than in placebo treated patients include somnolence and irritability 6 1 To report SUSPECTED ADVERSE REACTIONS contact UCB Inc at 866 822 0068 or FDA at 1 800 FDA 1088 or www fda gov medwatch USE IN SPECIFIC POPULATIONS 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 8 8 1 See 17 for PATIENT COUNSELING INFORMATION and Medication Guide Revised 08 2014 FULL PRESCRIBING INFORMATION CONTENTS 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2 1 General Dosing Recommendations 2 2 Adult Patients with Impaired Renal Function 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5 1 Psychiatric Reactions 5 2 Suicidal Behavior and Ideation 5 3 Somnolence and Fatigue 5 4 Serious Dermatological Reactions 5 5 Coordination Difficulties 5 6 Withdrawal Seizures 5 7 Hematologic Abnormalities 5 8 Seizure Control During Pregnancy 6 ADVERSE REACTIONS 6 1 Clinical Trials Experience 6 2 Postmarketing Experience 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8 1 Pregnancy 8 2 Labor and Delivery 8 3 Nursing Mothers 8 4 Pediatric Use 8 5 Geriatric Use 8 6 Use in Patients with Impaired Renal Function 10 OVERDOSAGE 10 1 Signs Symptoms and Laboratory Findings of Acute Overdosage in Humans 10 2 Management of Overdose 10 3 Hemodialysis 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12 1 Mechanism of Action 12 2 Pharmacodynamics 12 3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13 1 Carcinogenesis Mutagenesis Impairment of Fertility 14 CLINICAL STUDIES 14 1 KEPPRA XR in Adults 14 2 Immediate release KEPPRA in Adults 14 3 Immediate release KEPPRA in Pediatric Patients 16 HOW SUPPLIED STORAGE AND HANDLING 16 1 How Supplied 16 2 Storage 17 PATIENT COUNSELING INFORMATION Sections or subsections omitted from the Full Prescribing Information are not listed Reference ID 3605315 KEPPRA XR NDA 022285 S 020 FDA Approved Labeling Text Aug 2014 1 INDICATIONS AND USAGE KEPPRA XR is indicated as adjunctive therapy in the treatment of partial onset seizures in patients 12 years of age with epilepsy 2 DOSAGE AND ADMINISTRATION 2 1 General Dosing Recommendations KEPPRA XR is administered once daily Treatment should be initiated 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 once daily dose of 3000 mg 2 2 Adult Patients with Impaired Renal Function KEPPRA XR dosing must be individualized according to the patient s renal function status Recommended doses and adjustment for dose for adults 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 140 age years x weight kg x 0 85 for female CLcr 72 x serum creatinine mg dL patients Then CLcr is adjusted for body surface area BSA as follows CLcr mL min CLcr mL min 1 73m2 x 1 73 BSA subject m2 Table 1 Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance mL min 1 73m2 Dosage mg Fre