Sign Out
Julitam: Tablet: Discontinuation: In accordance with current clinical practice, if Levetiracetam has to be discontinued, it is recommended to withdraw it gradually.
Renal insufficiency: The administration of Levetiracetam to patients with renal impairment may require dose adjustment. In patients with severely impaired hepatic function, assessment of renal function is recommended before dose selection.
Suicide: Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with levetiracetam. A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known. Therefore, patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.
Effects on Ability to Drive and Use Machines: No studies on the effects on the ability to drive and use machines have been performed. Due to possible different individual sensitivity, some patients might experience somnolence or other central nervous system related symptoms, especially at the beginning of treatment or following a dose increase. Therefore, caution is recommended in those patients when performing skilled tasks, e.g. driving vehicles or operating machinery. Patients are advised not to drive or use machines until it is established that their ability to perform such activities is not affected.
Oral solution: Hematologic Abnormalities: Partial Onset Seizures: Adults: 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 levetiracetam -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: Minor, but statistically significant, decreases in WBC and neutrophil counts were seen in levetiracetam -treated patients as compared to placebo. The mean decreases from baseline in the levetiracetam -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 levetiracetam-treated patients, compared to a decrease of 4% in placebo patients (statistically significant).
In the well-controlled trial, more levetiracetam-treated patients had a possibly clinically significant abnormally low WBC value (3.0% levetiracetam-treated versus 0% placebo), however, there was no apparent difference between treatment groups with respect to neutrophil count (5.0% levetiracetam-treated versus 4.2% placebo). No patient was discontinued secondary to low WBC or neutrophil counts.
Juvenile Myoclonic Epilepsy: Although 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.
Hepatic Abnormalities: There were no meaningful changes in mean liver function tests (LFT) in controlled trials in adult or pediatric patients; lesser LFT abnormalities were similar in drug and placebo treated patients in controlled trials (1.4%). No adult or pediatric patients were discontinued from controlled trials for LFT abnormalities except for 1 (0.07%) adult epilepsy patient receiving open treatment.
Patients, their caregivers, and families should be counseled that AEDs, including levetiracetam, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of 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.
Patients should be advised that levetiracetam may cause changes in behavior (e.g. aggression, agitation, anger, anxiety, apathy, depression, hostility, and irritability) and in rare cases patients may experience psychotic symptoms.
Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry if they become pregnant. UCB, Inc. has established the UCB AED Pregnancy Registry to advance scientific knowledge about safety and outcomes associated with pregnant women being treated with all UCB antiepileptic drugs, including levetiracetam.
Patients should be advised that levetiracetam may cause dizziness and somnolence. Accordingly, patients should be advised not to drive or operate machinery or engage in other hazardous activities until they have gained sufficient experience on levetiracetam to gauge whether it adversely affects their performance of these activities.
Laboratory Tests: Although most laboratory tests are not systematically altered with levetiracetam treatment, there have been relatively infrequent abnormalities seen in hematologic parameters and liver function tests.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenesis: Rats were dosed with levetiracetam in the diet for 104 weeks at doses of 50, 300 and 1800 mg/kg/day. The highest dose corresponds to 6 times the maximum recommended daily human dose (MRHD) of 3000 mg on a mg/m2 basis and it also provided systemic exposure (AUC) approximately 6 times that achieved in humans receiving the MRHD. There was no evidence of carcinogenicity. A study was conducted in which mice received levetiracetam in the diet for 80 weeks at doses of 60, 240 and 960 mg/kg/day (high dose is equivalent to 2 times the MRHD on a mg/m2 or exposure basis). Although no evidence for carcinogenicity was seen, the potential for a carcinogenic response has not been fully evaluated in that species because adequate doses have not been studied.
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.
Use in Patients with Impaired Renal Function: Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance. 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 levetiracetam and supplemental doses should be given to patients after dialysis.
Julitam I.V.: The recommendation in accordance with the current clinical experience is the termination of JULITAM I.V. treatment with a gradual dose reduction. (For example: in adults and adolescents over 50 kg, reducing 2 x 500 mg/day every 2-4 weeks; in children and adolescents under 50 kg; 2 x 10 mg/kg/day dose every 2 weeks. Not to exceed the condition).
Acute kidney injury: Levetiracetam use is rarely associated with acute renal injury, and the onset time ranges from several days to several months.
Renal impairment: Dose adjustment may be required in patient with renal impairment. Therefore, in patients with severe hepatic impairment, assessment of renal function is recommended before dose selection (see Dosage & Administration).
Blood cell counts: Sparse cases with a decrease in blood cell counts (neutropenia, agranulocytosis, leukopenia, thrombocytopenia and pancytopenia) have been generally described in connection with levetiracetam administration at the beginning of treatment. Whole blood cell count is recommended in patients experiencing significant weakness, pyrexia, recurrent infections and coagulation disorders.
Suicide: Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known. Therefore patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients and caregivers of patients should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.
Excipients: This medicinal product contains 2.5 mmol (or 57 mg) sodium per maximum single dose [or 0.8 mmol (or 19 mg) per vial]. The sodium content should be taken into account in patients on a controlled sodium diet.
Effects on Ability to Drive and Use Machines: Levetiracetam has a minor or moderate effect on vehicle and machine use. Thus, drowsiness or other central nervous system-related symptoms may occur due to different individual sensitivities, especially at the beginning of treatment or in dose increases. For this reason, it is necessary for people to perform tasks requiring skills eg, it is recommended that vehicle drivers and machine operators be careful. It is not recommended to use tools or machinery until it is determined that the skills of the patients performing such activities are not affected.
Use in Pregnancy & Lactation: See Use in Pregnancy & Lactation for further information.
Use in Children: Julitam: Tablet: The tablet formulation is not adapted for use in infants and children under the age of 6 years.
Available data in children did not suggest impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
Oral solution: Safety and effectiveness in patients below 4 years of age have not been established.
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 1800 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.
Julitam I.V.: Available data in children did not suggest impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
As in adults, there is no clinically significant evidence of drug interaction in pediatric patients treated with doses up to 60 mg/kg/day.
A retrospective assessment of pharmacokinetic interactions in children and adolescents with epilepsy (4 to 17 years) confirmed that adjunctive therapy with orally administered levetiracetam did not influence the steady-state serum concentrations of concomitantly administered carbamazepine and valproic acid. However, data suggested a 20% higher levetiracetam clearance in children taking enzyme-inducing antiepileptic medicinal products. Dosage adjustment is not required.
Use in the Elderly: Julitam: Oral solution: Of the total number of subjects in clinical studies of 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 levetiracetam 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.
