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核准日期:修改日期：左乙拉西坦片使用说明书请仔细阅读说明书并在医生指导下使用【药品名称】通用名称：左乙拉西坦片商品名称：开浦兰(Keppra)英文名称：Levetiracetam Tablets汉语拼音：Zuoyilaxitan Pian【成份】主要组成成分本品的活性成份为左乙拉西坦，其化学名称为(S)-α-乙基-2-氧代-1-吡咯烷乙酰胺分子式：C8H14N2O2分子量：170.21【性状】本品为椭圆形薄膜包衣片（250mg为蓝色片，500mg为黄色片，1000mg为白色片），除去包衣后均显白色。
【适应症】用于成人及4岁以上儿童癫痫患者部分性发作的加用治疗。
【规格】（1） 0.25g (2) 0.5g （3） 1.0g【用法用量】(1) 给药途径: 口服。
需以适量的水吞服，服用不受进食影响。
(2) 给药方法和剂量成人（>18岁）和青少年（12岁~17岁）体重≥50kg起始治疗剂量为每次500mg,每日 2次。
根据临床效果及耐受性,每日剂量可增加至每次1500mg,每日两次。
剂量的变化应每2-4周增加或减少500mg/次, 每日2次。
老年人 (≥65岁)根据肾功能状况，调整剂量 (详见下文有关肾功能受损病人描述)。
4~11岁的儿童和青少年（12-17岁）体重≤50kg起始治疗剂量是10mg/kg，每日两次。
根据临床效果及耐受性，剂量可以增加至30mg/kg，每日两次。
剂量变化应以每两周增加或减少10mg/kg,每日两次。
应尽量使用最低有效剂量。
儿童和青少年体重≥50kg,剂量和成人一致。
青少年和儿童推荐剂量20kg 以下的儿童，为精确调整剂量，起始治疗应使用口服溶液。
婴儿和小于4岁的儿童患者目前尚无相关的充足的资料。
肾功能受损的病人成人肾功能受损病人，根据肾功能状况，按表中不同肌苷清除率(CLcr)ml/min(测出血清肌苷值按下述计算方法)调整日剂量.。
肾功能受损病人的剂量(1)服用第一天推荐负荷剂量为左乙拉西坦750mg。
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use KEPPRA® safely and effectively. See full prescribing information for KEPPRA.KEPPRA (levetiracetam) tablets, for oral useKEPPRA (levetiracetam) oral solutionInitial U.S. Approval: 1999----------------------------INDICATIONS AND USAGE--------------------------KEPPRA is an antiepileptic drug indicated for adjunctive therapy in the treatment of:• Partial onset seizures in patients one month of age and older with epilepsy (1.1)• Myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy (1.2)• Primary generalized tonic-clonic seizures in patients 6 years of age and older with idiopathic generalized epilepsy (1.3)----------------------DOSAGE AND ADMINISTRATION----------------------• Use the oral solution for pediatric patients with body weight ≤ 20 kg(2.1).• For pediatric patients, use weight-based dosing for the oral solution witha calibrated measuring device (not a household teaspoon or tablespoon)(2.1)Partial Onset Seizures• 1 Month to < 6 Months: 7 mg/kg twice daily, increase in increments of 7 mg/kg twice daily every 2 weeks to recommended dose of 21 mg/kgtwice daily (2.2)• 6 Months to < 4 Years: 10 mg/kg twice daily, increase in increments of10 mg/kg twice daily every 2 weeks to recommended dose of 25 mg/kgtwice daily (2.2)• 4 Years to < 16 Years: 10 mg/kg twice daily, increase in increments of10 mg/kg twice daily every 2 weeks to recommended dose of 30 mg/kgtwice daily (2.2)• Adults 16 Years and Older: 500 mg twice daily, increase as needed and tolerated in increments of 500 mg twice daily every 2 weeks to a maximum recommended dose of 1500 mg twice daily (2.2)Myoclonic Seizures in Adults and Pediatric Patients 12 Years and Older• 500 mg twice daily, increase by 500 mg twice daily every 2 weeks to recommended dose of 1500 mg twice daily (2.3) Primary Generalized Tonic-Clonic Seizures• 6 Years to < 16 Years: 10 mg/kg twice daily, increase in increments of 10 mg/kg twice daily every 2 weeks to recommended dose of 30 mg/kg twice daily (2.4)• Adults 16 Years and Older: 500 mg twice daily, increase by 500 mg twice daily every 2 weeks to recommended dose of 1500 mg twice daily (2.4) Adult Patients with Impaired Renal Function• Dose adjustment is recommended, based on the patient’s estimated creatinine clearance (2.5, 8.6)---------------------DOSAGE FORMS AND STRENGTHS---------------------• 250 mg, 500 mg, 750 mg, and 1000 mg film-coated, scored tablets (3) • 100 mg/mL solution (3)-------------------------------CONTRAINDICATIONS-----------------------------• None (4)-----------------------WARNINGS AND PRECAUTIONS-----------------------• Psychiatric Symptoms: 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)• 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 (5.3)• Withdrawal Seizures: KEPPRA must be gradually withdrawn (5.6)------------------------------ADVERSE REACTIONS------------------------------Most common adverse reactions (incidence in KEPPRA-treated patients is ≥ 5% more than in placebo-treated patients) include:• Adult patients: somnolence, asthenia, infection and dizziness (6.1)• Pediatric patients: fatigue, aggression, nasal congestion, decreased appetite, and irritability (6.1)To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 866-822-0068 or FDA at 1-800-FDA-1088 or /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 (5.9, 8.1)See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.Revised: 08/2014FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE1.1 Partial Onset Seizures1.2 Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy1.3 Primary Generalized Tonic-Clonic Seizures2 DOSAGE AND ADMINISTRATION2.1 Important Administration Instructions2.2 Partial Onset Seizures2.3 Myoclonic Seizures in Patients 12 Years of Age and Older WithJuvenile Myoclonic Epilepsy2.4 Primary Generalized Tonic-Clonic Seizures2.5 Adult Patients with Impaired Renal Function3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Psychiatric Reactions5.2 Suicidal Behavior and Ideation5.3 Somnolence and Fatigue5.4 Serious Dermatological Reactions5.5 Coordination Difficulties5.6 Withdrawal Seizures5.7 Hematologic Abnormalities5.8 Blood Pressure Increases5.9 Seizure Control During Pregnancy6 ADVERSE REACTIONS6.1 Clinical Trials Experience6.2 Postmarketing Experience7 DRUG INTERACTIONS8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.2 Labor and Delivery8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Use in Patients with Impaired Renal Function10 OVERDOSAGE10.1 Signs, Symptoms and Laboratory Findings of AcuteOverdosage in Humans10.2 Management of Overdose10.3 Hemodialysis11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES14.1 Partial Onset Seizures14.2 Myoclonic Seizures in Patients with Juvenile MyoclonicEpilepsy14.3 Primary Generalized Tonic-Clonic Seizures16 HOW SUPPLIED/STORAGE AND HANDLING16.1 How Supplied16.2 Storage17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the Full Prescribing Information are not listed.1 INDICATIONS AND USAGE1.1 Partial Onset SeizuresKEPPRA is indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 1 month of age and older with epilepsy.1.2 Myoclonic Seizures in Patients with Juvenile Myoclonic EpilepsyKEPPRA is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.1.3 Primary Generalized Tonic-Clonic SeizuresKEPPRA is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.2 DOSAGE AND ADMINISTRATION2.1 Important Administration InstructionsKEPPRA is given orally with or without food. The KEPPRA dosing regimen depends on the indication, age group, dosage form (tablets or oral solution), and renal function.Prescribe the oral solution for pediatric p atients with body weight ≤ 20 kg. Prescribe the oral solution or tablets for pediatric patients with body weight above 20 kg.When using the oral solution in pediatric patients, dosing is weight-based (mg per kg) using a calibrated measuring device (not a household teaspoon or tablespoon).KEPPRA tablets should be swallowed whole. KEPPRA tablets should not be chewed or crushed.2.2 Partial Onset SeizuresAdults 16 Years and OlderIn clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose [see Clinical Studies (14.1)], a consistent increase in response with increased dose has not been shown.Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.Pediatric Patients1 Month to < 6 MonthsTreatment should be initiated with a daily dose of 14 mg/kg in 2 divided doses (7 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 14 mg/kg to the recommended daily dose of 42 mg/kg(21 mg/kg twice daily). In the clinical trial, the mean daily dose was 35 mg/kg in this age group. Theeffectiveness of lower doses has not been studied.6 Months to <4 Years:Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased in 2 weeks by an increment of 20 mg/kg to the recommended daily dose of 50 mg/kg (25 mg/kg twice daily). If a patient cannot tolerate a daily dose of 50 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 47 mg/kg in this age group.4 Years to < 16 YearsTreatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical efficacy trial, the mean daily dose was 44 mg/kg. The maximum daily dose was 3000 mg/day.For KEPPRA tablet dosing in pediatric patients weighing 20 to 40 kg, treatment should be initiated with a daily dose of 500 mg given as twice daily dosing (250 mg twice daily). The daily dose should be increased every 2 weeks by increments of 500 mg to a maximum recommended daily dose of 1500 mg (750 mg twice daily).For KEPPRA tablet dosing in pediatric patients weighing more than 40 kg, treatment should be initiated with a daily dose of 1000 mg/day given as twice daily dosing (500 mg twice daily). The daily dose should be increased every 2 weeks by increments of 1000 mg/day to a maximum recommended daily dose of 3000 mg (1500 mg twice daily).KEPPRA Oral Solution Weight-Based Dosing Calculation For Pediatric PatientsThe following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients:Daily dose (mg/kg/day) x patient weight (kg)Total daily dose (mL/day) = ----------------------------------------100 mg/mL2.3 Myoclonic Seizures in Patients 12 Years of Age and Older with Juvenile Myoclonic EpilepsyTreatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.2.4 Primary Generalized Tonic-Clonic SeizuresAdults 16 Years and OlderTreatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.Pediatric Patients Ages 6 to <16 YearsTreatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with bo dy weight ≤20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution [see Dosage and Administration (2.1)]. Only whole tablets should be administered.2.5 Adult Patients with Impaired Renal FunctionKEPPRA 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 forpatients 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 femaleCLcr=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 1.73BSA subject (m2)Table 1: Dosing Adjustment Regimen For Adult Patients With Impaired Renal FunctionGroup Creatinine Clearance(mL/min/1.73m2)Dosage (mg) FrequencyNormal > 80 500 to 1,500 Every 12 hoursMild 50 – 80 500 to 1,000 Every 12 hoursModerate 30 – 50 250 to 750 Every 12 hoursSevere ESRD patients < 30---250 to 500500 to 1,0001Every 12 hoursEvery 24 hours1using dialysis1 Following dialysis, a 250 to 500 mg supplemental dose is recommended.3 DOSAGE FORMS AND STRENGTHSKEPPRA 250 mg tablets are blue, oblong-shaped, scored, film-coated, and debossed with "ucb 250" on one side.KEPPRA 500 mg tablets are yellow, oblong-shaped, scored, film-coated, and debossed with "ucb 500" on one side.KEPPRA 750 mg tablets are orange, oblong-shaped, scored, film-coated, and debossed with "ucb 750" on one side.KEPPRA 1000 mg tablets are white, oblong-shaped, scored, film-coated, and debossed with “ucb 1000” on one side.KEPPRA 100 mg/mL oral solution is a clear, colorless, grape-flavored liquid.4 CONTRAINDICATIONSNone.5 WARNINGS AND PRECAUTIONS5.1 Psychiatric ReactionsIn some patients KEPPRA causes behavioral abnormalities. The incidences of behavioral abnormalities in the myoclonic and primary generalized tonic-clonic seizure studies were comparable to those of the adult and pediatric partial onset seizure studies.A total of 13.3% of adult KEPPRA-treated patients and 37.6% of pediatric KEPPRA-treated patients (4 to 16years of age) compared to 6.2% and 18.6% of adult and pediatric placebo patients respectively, experienced non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personalitydisorder). A randomized double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of KEPPRA as adjunctive therapy in pediatric patients (4 to 16 years of age). The results from an exploratory analysis indicated a worsening in KEPPRA-treated patients on aggressive behavior (one of eight behavior dimensions) as measured in a standardized and systematic way using a validated instrument, the Achenbach Child Behavior Checklist (CBCL/6-18).In pediatric patients 1 month to < 4 years of age, irritability was reported in 11.7% of the KEPPRA-treated patients compared to 0% of placebo patients.A total of 1.7% of adult KEPPRA-treated patients discontinued treatment due to behavioral adverse events, compared to 0.2% of placebo patients. The treatment dose was reduced in 0.8% of adult KEPPRA-treated patients and in 0.5% of placebo patients. Overall, 10.9% of KEPPRA-treated pediatric patients experienced behavioral symptoms associated with discontinuation or dose reduction, compared to 6.2% of placebo patients. One percent of adult KEPPRA-treated patients, 2% of children 4 to 16 years of age, and 17% of children 1 month to <4 years of age experienced psychotic symptoms, compared to 0.2%, 2%, and 5% respectively, in the placebo patients. In the controlled study that assessed the neurocognitive and behavioral effects of KEPPRA in pediatric patients 4 to 16 years of age, 1 (1.6%) KEPPRA-treated patient experienced paranoia compared to no placebo patients. There were 2 (3.1%) KEPPRA-treated patients that experienced confusional state compared to no placebo patients [see Use in Specific Populations (8.4)].Two (0.3%) adult KEPPRA-treated patients were hospitalized and their treatment was discontinued due to psychosis. Both events, reported as psychosis, 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 the pediatric patients who discontinued treatment due to psychotic and non-psychotic adverse reactions.The above psychiatric signs and symptoms should be monitored.5.2 Suicidal Behavior and IdeationAntiepileptic drugs (AEDs), including KEPPRA, 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 (5-100 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 analysisIndication PlaceboPatients withEvents Per1000Patients DrugPatients withEvents Per1000PatientsRelative Risk:Incidence of Eventsin DrugPatients/Incidencein Placebo PatientsRisk Difference:Additional DrugPatients withEvents Per 1000PatientsEpilepsy 1.0 3.4 3.5 2.4Psychiatric 5.7 8.5 1.5 2.9Other 1.0 1.8 1.9 0.9Total 2.4 4.3 1.8 1.9The 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 KEPPRA or any other AED must balance the risk of suicidal thoughts or behaviors 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.5.3 Somnolence and FatigueIn some patients, KEPPRA causes somnolence and fatigue. The incidences of somnolence and fatigue provided below are from controlled adult partial onset seizure studies. In general, the incidences of somnolence and fatigue in the pediatric partial onset seizure studies, and in pediatric and adult myoclonic and primary generalized tonic-clonic 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 KEPPRA-treated patients reported somnolence, compared to 8.4% of placebo patients. There was no clear dose response up to 3000 mg/day. In a study where there was no titration, about 45% of patients receiving 4000 mg/day reported somnolence. The somnolence was considered serious in 0.3% of the treated patients, compared to 0% in the placebo group. About 3% of KEPPRA-treated patients discontinued treatment due to somnolence, compared to 0.7% of placebo patients. In 1.4% of treated patients and in 0.9% of placebo patients the dose was reduced, while 0.3% of the treated patients were hospitalized due to somnolence.In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.7% of KEPPRA-treated patients reported asthenia, compared to 9.1% of placebo patients. Treatment was discontinued due to asthenia in 0.8% of treated patients as compared to 0.5% of placebo patients. In 0.5% of treated patients and in 0.2% of placebo patients the dose was reduced due to asthenia.Somnolence and asthenia occurred most frequently within the first 4 weeks of treatment.Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on KEPPRA to gauge whether it adversely affects their ability to drive or operate machinery.5.4 Serious Dermatological ReactionsSerious 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. Keppra 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.5.5 Coordination DifficultiesCoordination difficulties were only observed in the adult partial onset seizure studies. A total of 3.4% of adult KEPPRA-treated patients experienced coordination difficulties, (reported as either ataxia, abnormal gait, or incoordination) compared to 1.6% of placebo patients. A total of 0.4% of patients in controlled trials discontinued KEPPRA treatment due to ataxia, compared to 0% of placebo patients. In 0.7% of treated patients and in 0.2% of placebo patients the dose was reduced due to coordination difficulties, while one of the treated patients was hospitalized due to worsening of pre-existing ataxia. These events occurred most frequently within the first 4 weeks of treatment.Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on KEPPRA to gauge whether it could adversely affect their ability to drive or operate machinery.5.6 Withdrawal SeizuresAntiepileptic drugs, including KEPPRA, should be withdrawn gradually to minimize the potential of increased seizure frequency.5.7 Hematologic AbnormalitiesPartial Onset SeizuresAdultsMinor, but statistically significant, decreases compared to placebo in total mean RBC count (0.03 x 106/mm3), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%), were seen in KEPPRA-treated patients in controlled trials.A total of 3.2% of treated and 1.8% of placebo patients had at least one possibly significant (≤2.8 x 109/L) decreased WBC, and 2.4% of treated and 1.4% of placebo patients had at least one possibly significant (≤1.0 x 109/L) decreased neutrophil count. Of the treated patients 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. Pediatric Patients 4 Years to < 16 YearsStatistically significant decreases in WBC and neutrophil counts were seen in KEPPRA-treated patients as compared to placebo. The mean decreases from baseline in the KEPPRA-treated group were -0.4 × 109/L and 0.3 × 109/L, respectively, whereas there were small increases in the placebo group. Mean relative lymphocyte counts increased by 1.7% in KEPPRA-treated patients, compared to a decrease of 4% in placebo patients (statistically significant).In the controlled trial, more KEPPRA-treated patients had a possibly clinically significant abnormally low WBC value (3.0% KEPPRA-treated versus 0% placebo), however, there was no apparent difference between treatment groups with respect to neutrophil count (5.0% KEPPRA-treated versus 4.2% placebo). No patient was discontinued secondary to low WBC or neutrophil counts.In the controlled cognitive and neuropsychological safety study, two subjects (6.1%) in the placebo group and 5 subjects (8.6%) in the KEPPRA-treated group had high eosinophil count values that were possibly clinically significant (≥10% or ≥0.7X109/L).Juvenile Myoclonic EpilepsyAlthough there were no obvious hematologic abnormalities observed in patients with JME, the limited number of patients makes any conclusion tentative. The data from the partial seizure patients should be considered to be relevant for JME patients.5.8 Blood Pressure IncreasesIn a randomized, placebo-controlled study in patients aged 1 month to <4 years of age, a significantly higher risk of at least one measured increase in diastolic blood pressure was observed in the KEPPRA-treated patients (17%) compared to the placebo-treated patients (2%). There was no overall difference in mean diastolic blood pressure between the treatment groups. This disparity between the KEPPRA and placebo treatment groups was not observed in the studies of older children or in adults.5.9 Seizure Control During PregnancyPhysiological 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.6 ADVERSE REACTIONSThe following adverse reactions are discussed in more details in other sections of labeling:•Psychiatric 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)]•Serious Dermatological Reactions [see Warnings and Precautions (5.4)]•Coordination Difficulties [see Warnings and Precautions (5.5)]•Withdrawal Seizures [see Warnings and Precautions (5.6)]•Hematologic Abnormalities [see Warnings and Precautions (5.7)]•Blood Pressure Increases [see Warnings and Precautions (5.8)]•Seizure Control During Pregnancy [see Warnings and Precautions (5.9)]6.1 Clinical Trials ExperienceBecause 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 tables, obtained when KEPPRA was 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.Partial Onset SeizuresAdults。
左乙拉西坦-注射液（5ml）说明书中文翻译左乙拉西坦注射液说明书参考译文近期主要变更剂量与用法，部分性发作（ 2.6 ）警告与注意事项（ 5.1、5.2 、5.3、5.4、5.7 ）适应症与应用当口服KEPPRA给药暂时不可行时，KEPPRA注射液是抗癫痫药物用于成人（》16 岁）以下发作类型的辅助治疗：部分性发作（ 1.1 ）少年肌阵挛癫痫患者的肌阵挛性发作（ 1.2）原发性强直性癫痫发作（ 1.3 ）剂量与给药方法KEPPRA注射液在使用前用100mL可配伍稀释剂稀释，滴注15min （2.1 ）。
初始使用KEPPRA （2.2）：部分性发作：1000mg/d ，每天2次（500mg，每天2 次），根据需要和耐受性每 2 周增加1000mg/d 至最大推荐日剂量3000mg/d 。
青少年肌阵挛性癫痫患者的肌阵挛性发作：初始剂量1000mg/d（500mg ，每天2次）。
每2周增加剂量1000mg/d 至推荐日剂量为3000mg/d ，尚未研究剂量低于3000mg/d 的有效性。
特发性全身强直阵挛发作：初始剂量1000mg/d （500mg ，每天 2 次）。
每 2 周增加剂量1000mg/d 至推荐日剂量3000mg/d ，尚未研究剂量低于3000mg/d 的有效性。
替代治疗（ 2.3）从口服KEPPRA 转向静脉注射剂量：开始静脉注射左乙拉西坦，总日剂量和频率与片剂相当。
在静滴治疗期结束时，患者可转用KEPPRA 口服给药，日剂量和频率与静脉注射左乙拉西坦相当。
剂量说明（ 2.5）、肾功能损害成人患者（ 2.6 ）和相容性和稳定性（ 2.7）见全部处方信息。
剂型和剂量500mg/5mL ，一次性小瓶（3 ）。
禁忌禁忌无警告与注意事项1 精神病反应：行为异常包括精神病症状、自杀意念、易激、攻击行为。
监测患者的精神病征兆和症状（ 5.1 ）。
嗜睡和疲乏：监测患者的这些症状，在未获得充分的经验前劝告患者不要驾驶汽车或操作机械（ 5.2）。
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese 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) tablet, film coated, extended release for oral useInitial U.S. Approval: 1999RECENT MAJOR CHANGESWarnings and Precautions (5.1)[04/2009] Patient Counseling Information (17)[04/2009]INDICATIONS AND USAGEKEPPRA XR is an antiepileptic drug indicated for adjunctive therapy in the treatment of partial onset seizures in patients ≥16 years of age with epilepsy (1)DOSAGE AND ADMINISTRATIONTreatment should be initiated with a dose of 1000 mg once daily. Thedaily dosage may be adjusted in increments of 1000 mg every 2 weeks to a maximum recommended daily dose of 3000 mg (2).See full prescribing information for use in patients with impaired renal function (2.1).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•Suicidal Behavior and Ideation. (5.1)•Neuropsychiatric Adverse Reactions: KEPPRA XR causes somnolence, dizziness, and behavioral abnormalities. The adverse reactions that may be seen in patients receiving KEPPRA XR tablets are expected to be similar to those seen in patients receiving immediate-release KEPPRA tablets. (5.2)•In controlled trials of immediate-release KEPPRA tablets in patients experiencing partial onset seizures, immediate-release KEPPRA causes somnolence and fatigue, coordination difficulties, and behavioral abnormalities (e.g., psychotic symptoms, suicidal ideation, and other abnormalities). (5.2)•Withdrawal Seizures: KEPPRA XR must be gradually withdrawn. (5.3)ADVERSE REACTIONS•Most common adverse reactions (difference in incidence rate is ≥5% between KEPPRA XR-treated patients and placebo-treated patients and occurred more frequently in KEPPRA XR-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 /medwatchTo report SUSPECTED ADVERSE REACTIONS, contact at or FDA at 1-800-FDA-1088 or /medwatchUSE IN SPECIFIC POPULATIONS•To enroll in the UCB AED Pregnancy Registry call 888-537-7734 (toll free). To enroll in the North American Antiepileptic Drug Pregnancy Registry call (888) 233-2334 (toll free). (8.1)• A dose adjustment is recommended for patients with impaired renal function, based on the patient's estimated creatinine clearance (8.6).See 17 for PATIENT COUNSELING INFORMATION and the FDA-approved Medication GuideRevised: 10/2009FULL PRESCRIBING INFORMATION: CONTENTS *1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION2.1 Adult Patients With Impaired Renal Function3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Suicidal Behavior and Ideation5.2 Neuropsychiatric Adverse Reactions5.3 Withdrawal Seizures5.4 Hematologic Abnormalities5.5 Hepatic Abnormalities5.6 Laboratory Tests6 ADVERSE REACTIONS6.1 Clinical Studies Experience6.2 Postmarketing Experience7 DRUG INTERACTIONS7.1 General Information7.2 Phenytoin7.3 Valproate7.4 Other Antiepileptic Drugs7.5 Oral Contraceptives7.6 Digoxin7.7 Warfarin7.8 Probenecid8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.2 Labor And Delivery8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Use In Patients With Impaired Renal Function9 DRUG ABUSE AND DEPENDENCE10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism Of Action12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility13.2 Animal Toxicology And/Or Pharmacology14 CLINICAL STUDIES16 HOW SUPPLIED/STORAGE AND HANDLING16.1 How Supplied16.2 Storage17 PATIENT COUNSELING INFORMATION* Sections or subsections omitted from the full prescribing information are not listedFULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGEKEPPRA XR™ is indicated as adjunctive therapy in the treatment of partial onset seizures in patients ≥16 years of age with epilepsy.2 DOSAGE AND ADMINISTRATIONTreatment should be initiated with a dose of 1000 mg once daily. The daily dosage may be adjusted in increments of 1000 mg every 2 weeks to a maximum recommended daily dose of 3000 mg.2.1 Adult Patients With Impaired Renal FunctionKEPPRA 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. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:[140-age (years)] x weight (kg)CLcr = ---------------------------------------------- x 1 0.8572 x serum creatinine (mg/dL)1. For female patientsThen CLcr is adjusted for body surface area (BSA) as follows:CLcr (mL/min)CLcr (mL/min/1.73m2) = ----------------------------- x 1.73BSA subject (m2)Table 1: Dosing Adjustment Regimen For Adult Patients With Impaired Renal FunctionGroup CreatinineClearance(mL/min/1.73m2) Dosage(mg)FrequencyNormal > 80 1000 to 3000 Every 24 hMild 50 – 80 1000 to 2000 Every 24 h Moderate 30 – 50 500 to 1500 Every 24 h Severe < 30 500 to 1000 Every 24 h3 DOSAGE FORMS AND STRENGTHSKEPPRA XR tablets are white, oblong-shaped, film-coated extended-release tablets imprinted in red with "UCB 500XR" on one side and contain 500 mg levetiracetam.KEPPRA XR tablets are white, oblong-shaped, film-coated extended-release tablets imprinted in red with "UCB 750XR" on one side and contain 750 mg levetiracetam.4 CONTRAINDICATIONSNone5 WARNINGS AND PRECAUTIONS5.1 Suicidal Behavior and IdeationAntiepileptic drugs (AEDs), including KEPPRA 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 (5-100 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 analysisIndication Placebo Patients withEvents Per 1000 PatientsDrug Patients withEvents Per 1000 PatientsRelative Risk: Incidenceof Events in DrugPatients/Incidence inPlacebo PatientsRisk DifferenceAdditional DrugPatients with Events Per1000 Patients Epilepsy 1.0 3.4 3.5 2.4Psychiatric 5.7 8.5 1.5 2.9Other 1.0 1.8 1.9 0.9Total 2.4 4.3 1.8 1.9The 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 KEPPRA 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.5.2 Neuropsychiatric Adverse ReactionsKEPPRA XR TabletsIn some patients experiencing partial onset seizures, KEPPRA XR causes somnolence, dizziness, and behavioral abnormalities.In the KEPPRA XR double-blind, controlled trial in patients experiencing partial onset seizures, 7.8% of KEPPRA XR-treated patients experienced somnolence compared to 2.5% of placebo-treated patients. Dizziness was reported in 5.2% of KEPPRA XR-treated patients compared to 2.5% of placebo-treated patients.A total of 6.5% of KEPPRA XR-treated patients experienced non-psychotic behavioral disorders (reported as irritability and aggression) compared to 0% of placebo-treated patients. Irritability was reported in 6.5% of KEPPRA XR-treated patients. Aggression was reported in 1.3% of KEPPRA XR-treated patients.No patient discontinued treatment or had a dose reduction as a result of these adverse reactions.The number of patients exposed to KEPPRA XR was considerably smaller than the number of patients exposed to immediate-release KEPPRA tablets in controlled trials. Therefore, certain adverse reactions observed in the immediate-release KEPPRA controlled trials may also occur in patients receiving KEPPRA XR.Immediate-Release KEPPRA TabletsIn controlled trials of immediate-release KEPPRA tablets in patients experiencing partial onset seizures, immediate-release KEPPRA causes the occurrence of central nervous system adverse reactions that can be classified into the following categories: 1) somnolence and fatigue, 2) coordination difficulties, and 3) behavioral abnormalities.In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.8% of immediate-release KEPPRA-treated patients reported somnolence, compared to 8.4% of placebo patients. There was no clear dose response up to 3000 mg/day.In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.7% of treated patients reported asthenia, compared to 9.1% of placebo patients.A total of 3.4% of immediate-release KEPPRA-treated patients experienced coordination difficulties, (reported as either ataxia, abnormal gait, or incoordination) compared to 1.6% of placebo patients.Somnolence, asthenia and coordination difficulties occurred most frequently within the first 4 weeks of treatment.In controlled trials of patients with epilepsy experiencing partial onset seizures, 5 (0.7%) immediate-release KEPPRA-treated patients experienced psychotic symptoms compared to 1 (0.2%) placebo patient.A total of 13.3% of immediate-release KEPPRA patients experienced other behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.) compared to 6.2% of placebo patients.5.3 Withdrawal SeizuresAntiepileptic drugs, including KEPPRA XR, should be withdrawn gradually to minimize the potential of increased seizure frequency.5.4 Hematologic AbnormalitiesAlthough there were no obvious hematologic abnormalities observed in treated patients in the KEPPRA XR controlled study, the limited number of patients makes any conclusion tentative. The data from the partial seizure patients in the immediate-release KEPPRA controlled studies should be considered to be relevant for KEPPRA XR-treated patients.In controlled trials of immediate-release KEPPRA tablets in patients experiencing partial onset seizures, minor, but statistically significant, decreases compared to placebo in total mean RBC count (0.03 x 106/mm3), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%), were seen in immediate-release KEPPRA-treated patients. A total of 3.2% of treated and 1.8% of placebo patients had at least one possibly significant (≤2.8 x 109/L) decreased WBC, and 2.4% of treated and 1.4% of placebo patients had at least one possibly significant (≤1.0 x 109/L) decreased neutrophil count. Of the treated patients 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.5.5 Hepatic AbnormalitiesThere were no meaningful changes in mean liver function tests (LFT) in the KEPPRA XR controlled trial. No patients were discontinued from the controlled trial for LFT abnormalities.There were no meaningful changes in mean liver function tests (LFT) in controlled trials of immediate-release KEPPRA tablets in adult patients; lesser LFT abnormalities were similar in drug and placebo-treated patients in controlled trials (1.4%). No patients were discontinued from controlled trials for LFT abnormalities except for 1 (0.07%) adult epilepsy patient receiving open treatment.5.6 Laboratory TestsAlthough effects on laboratory tests were not clinically significant with KEPPRA XR treatment, it is expected that the data from immediate-release KEPPRA tablets controlled studies would be considered relevant for KEPPRA XR-treated patients.Although most laboratory tests are not systematically altered with immediate-release KEPPRA treatment, there have been relatively infrequent abnormalities seen in hematologic parameters and liver function tests.6 ADVERSE REACTIONS6.1 Clinical Studies ExperienceBecause 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 KEPPRA XR was added to concurrent AED therapy, cannot be used to predict the frequency of adverse experiences in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. 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.KEPPRA XR TabletsIn the well-controlled clinical study using KEPPRA XR in patients with partial onset seizures, the most frequently reported adverse reactions in patients receiving KEPPRA XR in combination with other AEDs, not seen at an equivalent frequency among placebo-treated patients, were irritability and somnolence.Table 3 lists treatment-emergent adverse reactions that occurred in at least 5% of epilepsy patients treated with KEPPRA XR participating in the placebo-controlled study and were numerically more common than in patients treated with placebo. In this study, either KEPPRA XR or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity. Table 3: Incidence (%) Of Treatment-Emergent Adverse Reactions In The Placebo-Controlled, Add-On Study By Body System (Adverse Reactions Occurred In At Least 5% Of KEPPRA XR-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)Body System/ Adverse Reaction KEPPRA XR(N=77)%Placebo(N=79)%Gastrointestinal DisordersNausea 5 3Infections and InfestationsInfluenza 8 4Nasopharyngitis 7 5Nervous System DisordersSomnolence 8 3Dizziness 5 3Psychiatric DisordersIrritability 7 0 Discontinuation Or Dose Reduction In The KEPPRA XR Well-Controlled Clinical StudyIn the well-controlled clinical study using KEPPRA XR, 5.2% of patients receiving KEPPRA XR and 2.5% receiving placebo discontinued as a result of an adverse event. The adverse reactions that resulted in discontinuation and that occurred more frequently in KEPPRA XR-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 KEPPRA XR-treated patient and no placebo-treated patients. Comparison Of Gender, Age And RaceThere are insufficient data for KEPPRA XR to support a statement regarding the distribution of adverse experience reports by gender, age and race.Table 4 lists the adverse reactions seen in the well-controlled studies of immediate-release KEPPRA tablets in adult patients experiencing partial onset seizures. Although the pattern of adverse reactions in the KEPPRA XR study seems somewhat different from that seen in partial onset seizure well-controlled studies for immediate-release KEPPRA 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 KEPPRA XR are expected to be similar to those seen with immediate-release KEPPRA tablets.Immediate-Release KEPPRA TabletsIn well-controlled clinical studies of immediate-release KEPPRA tablets as adjunctive therapy to other AEDs in adults with partial onset seizures, the most frequently reported adverse reactions, not seen at an equivalent frequency among placebo-treated patients, were somnolence, asthenia, infection and dizziness.Table 4 lists treatment-emergent adverse reactions that occurred in at least 1% of adult epilepsy patients treated with immediate-release KEPPRA tablets participating in placebo-controlled studies and were numerically more common than in patients treatedwith placebo. In these studies, either immediate-release KEPPRA tablets or placebo was added to concurrent AED therapy. Adverse reactions were usually mild to moderate in intensity.Table 4: Incidence (%) Of Treatment-Emergent 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 KEPPRA-Treated Patients And Occurred More Frequently Than Placebo-Treated Patients)Body System/ Adverse Reaction Immediate-release KEPPRA(N=769)%Placebo(N=439)%Body as a WholeAsthenia 15 9Headache 14 13Infection 13 8Pain 7 6Digestive SystemAnorexia 3 2Nervous SystemSomnolence 15 8Dizziness 9 4Depression 4 2Nervousness 4 2Ataxia 3 1Vertigo 3 1Amnesia 2 1Anxiety 2 1Hostility 2 1Paresthesia 2 1Emotional Lability 2 0Respiratory SystemPharyngitis 6 4Rhinitis 4 3Cough Increased 2 1Sinusitis 2 1Special SensesDiplopia 2 1In addition, the following adverse reactions were seen in other well-controlled studies of immediate-release KEPPRA tablets: balance disorder, disturbance in attention, eczema, hyperkinesia, memory impairment, myalgia, personality disorders, pruritus, and vision blurred.6.2 Postmarketing ExperienceIn addition to the adverse reactions listed above for immediate-release KEPPRA tablets [see Adverse Reactions (6.1)], the following adverse events have been identified during postapproval use of immediate-release KEPPRA tablets. Because these events 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, hepatic failure, hepatitis, leukopenia, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression identified in some of these cases), thrombocytopenia and weight loss. Alopecia has been reported with immediate-release KEPPRA use; recovery was observed in majority of cases where immediate-release KEPPRA was discontinued.7 DRUG INTERACTIONS7.1 General InformationIn vitro data on metabolic interactions indicate that KEPPRA XR is unlikely to produce, or be subject to, pharmacokinetic interactions. Levetiracetam and its major metabolite, at concentrations well above C max levels achieved within the therapeutic dose range, are neither inhibitors of nor high affinity substrates for human liver cytochrome P450 isoforms, epoxide hydrolase or UDP-glucuronidation enzymes. In addition, levetiracetam does not affect the in vitro glucuronidation of valproic acid.Levetiracetam circulates largely unbound (<10% bound) to plasma proteins; clinically significant interactions with other drugs through competition for protein binding sites are therefore unlikely.Potential pharmacokinetic interactions were assessed in clinical pharmacokinetic studies (phenytoin, valproate, oral contraceptive, digoxin, warfarin, probenecid) and through pharmacokinetic screening with immediate-release KEPPRA tablets in the placebo-controlled clinical studies in epilepsy patients. The following are the results of these studies. The potential for drug interactions for KEPPRA XR is expected to be essentially the same as that with immediate-release KEPPRA tablets.7.2 PhenytoinImmediate-release KEPPRA tablets (3000 mg daily) had no effect on the pharmacokinetic disposition of phenytoin in patients with refractory epilepsy. Pharmacokinetics of levetiracetam were also not affected by phenytoin.7.3 ValproateImmediate-release KEPPRA tablets (1500 mg twice daily) did not alter the pharmacokinetics of valproate in healthy volunteers. Valproate 500 mg twice daily did not modify the rate or extent of levetiracetam absorption or its plasma clearance or urinary excretion. There also was no effect on exposure to and the excretion of the primary metabolite, ucb L057.7.4 Other Antiepileptic DrugsPotential drug interactions between immediate-release KEPPRA tablets and other AEDs (carbamazepine, gabapentin, lamotrigine, phenobarbital, phenytoin, primidone and valproate) were also assessed by evaluating the serum concentrations of levetiracetamand these AEDs during placebo-controlled clinical studies. These data indicate that levetiracetam does not influence the plasma concentration of other AEDs and that these AEDs do not influence the pharmacokinetics of levetiracetam.7.5 Oral ContraceptivesImmediate-release KEPPRA tablets (500 mg twice daily) did not influence the pharmacokinetics of an oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, or of the luteinizing hormone and progesterone levels, indicating that impairment of contraceptive efficacy is unlikely. Coadministration of this oral contraceptive did not influence the pharmacokinetics of levetiracetam.7.6 DigoxinImmediate-release KEPPRA tablets (1000 mg twice daily) did not influence the pharmacokinetics and pharmacodynamics (ECG) of digoxin given as a 0.25 mg dose every day. Coadministration of digoxin did not influence the pharmacokinetics of levetiracetam.7.7 WarfarinImmediate-release KEPPRA tablets (1000 mg twice daily) did not influence the pharmacokinetics of R and S warfarin. Prothrombin time was not affected by levetiracetam. Coadministration of warfarin did not affect the pharmacokinetics of levetiracetam.7.8 ProbenecidProbenecid, a renal tubular secretion blocking agent, administered at a dose of 500 mg four times a day, did not change the pharmacokinetics of levetiracetam 1000 mg twice daily. C ss max of the metabolite, ucb L057, was approximately doubled in the presence of probenecid while the fraction of drug excreted unchanged in the urine remained the same. Renal clearance of ucb L057 in the presence of probenecid decreased 60%, probably related to competitive inhibition of tubular secretion of ucb L057. The effect of immediate-release KEPPRA tablets on probenecid was not studied.8 USE IN SPECIFIC POPULATIONS8.1 PregnancyPregnancy Category CThere 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. KEPPRA XR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. As with other antiepileptic drugs, physiological changes during pregnancy may affect levetiracetam concentration. There have been reports of decreased levetiracetam concentration during pregnancy. Discontinuation of antiepileptic treatments may result in disease worsening, which can be harmful to the mother and 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 (approximately equivalent to the maximum recommended human dose of 3000 mg [MRHD] on a mg/m2 basis) and with increased pup mortality and offspring behavioral alterations at a dose of 1800 mg/kg/day (6 times the MRHD on a mg/m2 basis). The developmental no effect dose was 70 mg/kg/day (0.2 times the MRHD on a mg/m2 basis). 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 (approximately 4 times MRHD on a mg/m2 basis) and in decreased fetal weights and increased incidences of fetal malformations at a dose of 1800 mg/kg/day (12 times the MRHD on a mg/m2 basis). The developmental no effect dose was 200 mg/kg/day (1.3 times the MRHD on a mg/m2 basis). Maternal toxicity was also observed at 1800 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 3600 mg/kg/day (12 times the MRHD). 1200 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 1800 mg/kg/day (6 times the MRHD on a mg/m2 basis).Pregnancy RegistriesTo provide information regarding the effects of in utero exposure to KEPPRA XR, physicians are advised to recommend that pregnant patients taking KEPPRA 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 /.UCB, Inc. has established the UCB AED Pregnancy Registry to advance scientific knowledge about safety and outcomes in pregnant women being treated with all UCB antiepileptic drugs including KEPPRA XR. To ensure broad program access and reach, either a healthcare provider or the patient can initiate enrollment in the UCB AED Pregnancy Registry by calling (888) 537-7734 (toll free). 8.2 Labor And DeliveryThe effect of KEPPRA XR on labor and delivery in humans is unknown.8.3 Nursing MothersLevetiracetam is excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants from KEPPRA XR, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.8.4 Pediatric UseSafety and effectiveness of KEPPRA XR in patients below the age of 16 years have not been established.8.5 Geriatric UseThere were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of KEPPRA XR in these patients. It is expected that the safety of KEPPRA XR in elderly patients 65 and over would be comparable to the safety observed in clinical studies of immediate-release KEPPRA tablets.Of the total number of subjects in clinical studies of immediate-release levetiracetam, 347 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 KEPPRA in these patients.A study in 16 elderly subjects (age 61-88 years) with oral administration of single dose and multiple twice-daily doses of immediate-release KEPPRA tablets for 10 days showed no pharmacokinetic differences related to age alone.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.8.6 Use In Patients With Impaired Renal FunctionThe effect of KEPPRA XR on renally impaired patients was not assessed in the well-controlled study. However, it is expectedthat the effect on KEPPRA XR-treated patients would be similar to the effect seen in well-controlled studies of immediate-release KEPPRA tablets. Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing hemodialysis. The dosage should be reduced in patients with impaired renal function receiving KEPPRA XR [see Clinical Pharmacology (12.3) and Dosage and Administration (2.1)].Clearance of immediate-release levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance.9 DRUG ABUSE AND DEPENDENCEThe abuse and dependence potential of KEPPRA XR has not been evaluated in human studies.。
左乙拉西坦治疗儿童癫痫的疗效与安全性分析目的：观察左乙拉西坦（LEV）单药治疗小儿癫痫的疗效与安全性。
方法：回顾性分析笔者所在医院2009年12月-2012年12月儿童癫痫住院患者78例的临床资料。
结果：所有患者经过6个月随访，其中完全控制40例（51.3%），显效15例（19.2%），有效12例（15.4%），无效11例（14.1%），总有效率85.9%。
无不良反应者67例（85.9%），出现不良反应者11例（14.1%），不良反应：嗜睡4例（36.4%），疲乏3例（27.3%），兴奋3例（27.3%），头痛1例（9.1%）。
患者均未出现病情加重现象。
结论：左乙拉西坦单药治疗治疗儿童癫痫效果明显，不良反应出现少，安全性高，作为一种全新有效治疗癫痫药物，可成为临床中常规用药。
标签：左乙拉西坦；儿童癫痫；疗效；安全性儿童癫痫（cpilcpsy）属脑部疾病，病程发展较慢，临床表现为癫痫发作，并以突发性和一过性脑功能障碍为特点，是由脑神经元反复发作性异常放电引起的病变[1]。
目前，儿童癫痫的发病率较高，传统抗癫痫药物（卡马西平、地西泮、苯妥英等）临床副作用较多。
左乙拉西坦是2007年开始应用于临床治疗癫痫的新药，研究左乙拉西坦对儿童癫痫的治疗的疗效与安全性具有重要的临床意义。
本研究回顾性分析笔者所在医院2009年12月-2012年12月儿童癫痫住院患者应用左乙拉西坦治疗78例的临床资料，现报告如下。
1 资料与方法1.1 一般资料笔者所在医院2009年12月-2012年12月收治癫痫患儿78例，所有患儿诊断均符合《儿科学》中的诊断标准[1]。
78例患儿均属于新诊断病例，未曾予过抗癫痫药物治疗，均予服用LEV单药治疗，疗程≥6个月（最长疗程12个月）。
其中男49例，女29例，男女比1.69∶1；年龄6个月～16岁，其中<1岁15例，1～3岁23例，4～6岁21例，7～16岁19例；发作类型为部分性发作22例（简单部分性发作10例，复杂部分性发作9例，部分性发作继发全身性3例），全面强直性-阵挛性发作25例（强直性发作4例，阵挛性发作17例，全身强直-阵挛发作4例），肌阵挛发作16例，失神发作13例，West综合征2例。
左乙拉西坦片以下内容仅供参考，请以药品包装盒中的说明书为准。
妊娠：禁用哺乳：慎用核准日期：2014年06月06日修改日期：2014年07月01日左乙拉西坦片说明书请仔细阅读说明书并在医师指导下使用。
【药品名称】通用名称：左乙拉西坦片英文名称：Levetiracetam Tablets汉语拼音：Zuoyilaxitan Pian【成份】本品的活性成份为左乙拉西坦【性状】本品为薄膜衣片，除去包衣后显白色或类白色。
【适应症】用于成人及4岁以上儿童癫痫患者部分性发作的加用治疗。
【规格】0.5g【用法用量】（1）给药途径：口服。
需以适量的水吞服，服用不受进食影响。
（2）给药方法：成人(>18岁)和青少年(12~17岁)体重≥50 kg：起始治疗剂量为每次500 mg（即1片），每日2次。
根据临床效果及耐受性，每日剂量可增加至每次1500mg（即3片），每日2次。
剂量的变化应每2~4周增加或减少500 mg(即1片）/次，每日2次。
老年人 (≥65岁) ：根据肾功能状况，调整剂量 (详见下文有关肾功能受损病人描述)。
4~11岁的儿童和青少年(12~17岁)体重≤50 kg：起始治疗剂量10 mg/kg，每日2次。
根据临床效果及耐受性，剂量可以增加至30 mg/kg，每日2次。
剂量变化应以每2周增加或减少10 mg/kg，每日2次。
应尽量使用最低有效剂量。
儿童和青少年体重≥50 kg者，剂量和成人一致。
青少年和儿童推荐剂量：起始剂量10 mg/kg，每日2次，最大剂量30 mg/kg，每日2次。
青少年和儿童推荐剂量见表1：表1 青少年和儿童推荐剂量：体重起始剂量最大剂量15kg* 150mg/次，每日2次450mg/次，每日2次20kg 200 mg/次，每日2次600 mg/次，每日2次25kg 250 mg/次，每日2次750 mg/次，每日2次50kg 500 mg/次mg，每日2次1500 mg/次，每日2次*注：20 kg以下的儿童，为精确调整剂量，起始治疗应使用口服溶液。
核准日期：2006年11月22日修订日期：2016年04月29日左乙拉西坦片说明书请仔细阅读说明书并在医师指导下使用【药品名称】通用名称：左乙拉西坦片汉语拼音：Zuoyilaxitan Pian商品名称：开浦兰®(Keppra®)英文名称：Levetiracetam Tablets【成份】本品的活性成份为左乙拉西坦，其化学名称为(S)-α-乙基-2-氧代-1-吡咯烷乙酰胺化学结构式：分子式：C8H14N2O2分子量：170.21【性状】本品为蓝色（0.25g）或黄色（0.5g）或白色（1.0g）椭圆形薄膜包衣片，片剂的单面有刻痕，除去包衣后均显白色。
【适应症】用于成人及4岁以上儿童癫痫患者部分性发作的加用治疗。
【规格】（1）0.25g (2)0.5g （3）1.0g【用法用量】(1)给药途径：口服。
需以适量的水吞服，服用不受进食影响。
(2)给药方法和剂量成人（≥18岁）和青少年（12岁~17岁）体重≥50kg起始治疗剂量为500mg/次，每日2次。
根据临床效果及耐受性,每日剂量可增加至每次1500mg,每日两次。
剂量的变化应每2-4周增加或减少500mg，每日2次。
老年人(≥65岁)根据肾功能状况，调整剂量(详见下文有关肾功能受损病人描述)。
4~11岁的儿童和青少年（12~17岁）体重≤50kg起始治疗剂量是10mg/kg，每日两次。
根据临床效果及耐受性，剂量可以增加至30mg/kg，每日两次。
剂量变化应以每两周增加或减少10mg/kg,每日两次。
应尽量使用最低有效剂量。
儿童和青少年体重≥50kg,剂量和成人一致。
医生根据患者的体重、年龄和所需剂量，可推荐患者使用相应合适的剂型和规格。
青少年和*25kg以下的儿童，为精确调整剂量，起始治疗应使用口服溶液。
婴儿和小于4岁的儿童患者目前尚无相关的充足的资料。
肾功能受损的病人成人肾功能受损病人，根据肾功能状况，按表中不同肌苷清除率(CLcr)ml/min(测出血清肌苷值按下述计算方法)调整日剂量。
【药品名称】商品名：开浦兰汉语拼音：Zuoyilaxitan Pian通用名称：左乙拉西坦片英文名：Levetiracetam Tablets[编辑本段]【成份】左乙拉西坦的化学名称为(S)-α-乙基-2-氧代-1-吡咯烷乙酰胺，分子式：C8H14 N2O2，分子量：170.21。
[编辑本段]【性状】本品为椭圆形薄膜包衣片（250 mg为蓝色片，500 mg为黄色片，1000 mg为白色片），除去包衣后均显白色。
[编辑本段]【适应症】抗癫痫药，用于成人及4岁以上儿童癫痫患者部分性发作的加用治疗。
[编辑本段]【用法用量】（1）给药途径口服。
需以适量的水吞服，服用不受进食影响。
（2）给药方法和剂量成人（>18岁）和青少年（12-17岁）（体重≥ (greater than or equ al to) 50 kg者）：起始治疗剂量为每次500 mg，每日2次。
根据临床效果及耐受性，每日剂量可增加至每次1500 mg，每日2次。
剂量的变化应每2-4周增加或减少500 m g/次，每日2次。
老年人(≥ (greater than or equal to) 65岁) ：根据肾功能状况，调整剂量(详见下文有关肾功能受损病人描述)。
4-11岁的儿童和青少年（12-17岁）（体重≤ (smaller than or equal to) 50 kg者）：起始治疗剂量是10 mg/kg，每日2次。
根据临床效果及耐受性，剂量可以增加至30 mg/kg，每日2次。
剂量变化应以每2周增加或减少10 mg/kg，每日2次。
应尽量使用最低有效剂量。
儿童和青少年体重≥ (greater than or equal to) 50 kg者，剂量和成人一致。
青少年和儿童推荐剂量：起始剂量10 mg/kg，每日2次，最大剂量30 mg/kg，每日2次。
体重1 5 kg：起始剂量每次150 mg，每日2次，最大剂量每次450 mg，每日2次。
开浦兰(左乙拉西坦片)【药品名称】商品名称：开浦兰通用名称：左乙拉西坦片英文名称：Levetiracetam Tablets【成份】左乙拉西坦的化学名称为(S)-α-乙基-2-氧代-1-吡咯烷乙酰胺，分子式：C8H14N2O2，分子量：170.21。
【适应症】用于成人及4岁以上儿童癫痫患者部分性发作的加用治疗。
【用法用量】1.给药途径：口服。
需以适量的水吞服，服用不受进食影响。
2.给药方法和剂量：成人(>18岁)和青少年(12-17岁)(体重≥ (greater than or equal to) 50 kg者) ：起始治疗剂量为每次500 mg，每日2次。
根据临床效果及耐受性，每日剂量可增加至每次1500 mg，每日2次。
剂量的变化应每2-4周增加或减少500 mg/次，每日2次。
老年人(≥ (greater than or equal to) 65岁) ：根据肾功能状况，调整剂量(详见下文有关肾功能受损病人描述)。
4-11岁的儿童和青少年(12-17岁)(体重≤ (smaller than or equal to) 50 kg者) ：起始治疗剂量是10 mg/kg，每日2次。
根据临床效果及耐受性，剂量可以增加至30 mg/kg，每日2次。
剂量变化应以每2周增加或减少10 mg/kg，每日2次。
应尽量使用最低有效剂量。
儿童和青少年体重≥ (greater than or equal to) 50 kg者，剂量和成人一致。
青少年和儿童推荐剂量：起始剂量10 mg/kg，每日2次，最大剂量30 mg/kg，每日2次。
体重15 kg：起始剂量每次150 mg，每日2次，最大剂量每次450 mg，每日2次。
体重20 kg：起始剂量每次200 mg，每日2次，最大剂量每次600 mg，每日2次。
体重25 kg：起始剂量每次250 mg，每日2次，最大剂量每次750 mg，每日2次。
中国医学论坛报/2007年/4月/12日/第B12版神经强效控制长久无忧抗癫痫新药左乙拉西坦(开浦兰)上市中国逸文 吴逊左乙拉西坦(开浦兰)中国上市会于2007年3月10日在北京召开,本次会议的主题是“2007癫痫治疗:终极目标、无忧生活”。
吴逊、洪震、吴立文、周东和廖高概教授应邀出席了会议。
与会专家对开浦兰的疗效、安全性和作用机制等问题进行了深入讨论。
癫痫治疗终极目标:实现无发作北京协和医院吴立文教授指出,无发作是抗癫痫药物治疗的主要目标,实现无发作能降低癫痫患者死亡率,提高就业率,改善生活质量。
对于新诊断的癫痫患者,只有长期无发作才真正有意义。
对于难治性癫痫患者,获得短期无发作即可显著改善生活质量。
应根据癫痫发作类型和癫痫综合征正确选择抗癫痫药。
从小剂量开始,逐渐增加至维持量,发作控制不理想时应监测血药浓度。
先选用正确的抗癫痫药单药治疗,疗效不佳时再联合用药,以不超过3种为宜。
开浦兰中国注册临床试验结果显示,开浦兰用于成人及16岁以上青少年癫痫部分性发作的附加治疗,16周内,开浦兰组10.8%的患者无发作(安慰剂组仅有2%),发作频率降低≥50%的患者达55.9%,中度以上改善者达61%(图1)。
开浦兰组不良反应发生率与安慰剂组相似,未发生严重不良事件。
癫痫治疗终极目标:降低药物副作用华西医科大学附属医院周东教授提出,癫痫治疗的目标是在实现完全无发作的同时降低药物副作用,保持正常生活质量。
近年来抗癫痫药疗效增加,但仍有20%～30% 的患者发作难以控制或出现明显不良反应。
癫痫治疗要持续数年,故应选择耐受性最好、对生活质量负面影响最小的药物。
研究证实,开浦兰安全性好,不良反应少,多为轻中度,主要发生在治疗前4周内,导致减量或撤药的绝对比例很低。
长期治疗无肝、肾、血液及生化异常,不会产生耐药性,对认知功能无不良影响。
3年治疗保留率高达58%。
在儿童中,开浦兰的安全性与安慰剂相似。
未充分控制的部分性癫痫患儿(4～16岁)使用开浦兰作为辅助治疗,耐受性良好。
