Ivetra/Ivetra-100/Ivetra IV Adverse Reactions

Summary of the safety profile: The adverse event profile presented below is based on the analysis of pooled placebo-controlled clinical trials with all indications studied, with a total of 3,416 patients treated with levetiracetam. These data are supplemented with the use of levetiracetam in corresponding open-label extension studies, as well as post-marketing experience. The most frequently reported adverse reactions were nasopharyngitis, somnolence, headache, fatigue and dizziness. The safety profile of levetiracetam is generally similar across age groups (adult and paediatric patients) and across the approved epilepsy indications.
Tabulated list of adverse reactions Adverse reactions reported in clinical studies (adults, adolescents children and infants >1 month) and from post-marketing experience are listed in the following table per System Organ Class and per frequency. Very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000) and very rare (<1/10,000).
Infections and infestations: Very Common: nasopharyngitis; Rare: infection.
Blood and lymphatic system disorders: Uncommon: thrombocytopenia, leukopenia(1); Rare: neutropenia(1), pancytopenia(1,2).
Metabolism and nutrition disorders: Common: anorexia; Uncommon: weight decreased (1), weight increase.
Psychiatric disorders: Common: depression, anxiety(1), insomnia, nervousness/irritability; Uncommon: abnormal behaviour(1), anger(1), anxiety, confusional state(1), affect lability/mood swings, agitation, hallucination(1), psychotic disorder(1), suicide attempt(1), suicidal ideation(1); Rare: Completed suicide(1), personality disorder, thinking abnormal.
Nervous system disorders: Very common: somnolence; Common: Convulsion, balance disorder, dizziness, lethargy, tremor; Uncommon: amnesia, coordination abnormal/ataxia, disturbance in attention, memory impairment, paraesthesia(1); Rare: choreoathetosis(1), dyskinesia(1), hyperkinesia.
Eye disorders: Uncommon: diplopia, vision blurred.
Ear and labyrinth disorders: Common: vertigo.
Respiratory, thoracic and mediastinal disorders: Common: cough.
Gastrointestinal disorders: Common: abdominal pain, diarrhea, dyspepsia, nausea, vomiting; Rare: pancreatitis(1).
Hepatobiliary disorders: Uncommon:, liver function test abnormal(1); Rare: hepatic failure(1), hepatitis(1).
Skin and subcutaneous tissue disorders: Common: rash; Uncommon: Alopecia(1), eczema, pruritus; Rare: toxic epidermal necrolysis(1), Stevens-Johnson syndrome(1), erythema multiforme(1).
Musculoskeletal and connective tissue disorders: Uncommon: Muscular weakness, myalgia.
General disorders and administration site conditions: Common: asthenia/fatigue.
Injury, poisoning and procedural complications: Uncommon: injury.
(1) Adverse reactions added during post marketing experience.
(2) Bone marrow suppression identified in some of the cases.
Description of selected adverse reactions: The risk of anorexia is higher when topiramate is coadministered with levetiracetam.
In several cases of alopecia, recovery was observed when levetiracetam was discontinued.
Pediatric population: In patients aged 1 month to less than 4 years, a total of 190 patients have been treated with levetiracetam in placebo-controlled and open label extension studies. Sixty (60) of these patients were treated with levetiracetam in placebo-controlled studies. In patients aged 4-16 years, a total of 645 patients have been treated with levetiracetam in placebo-controlled and open label extension studies. 233 of these patients were treated with levetiracetam in placebo-controlled studies. In both these paediatric age ranges, these data are supplemented with the post-marketing experience of the use of levetiracetam.
The adverse event profile of levetiracetam is generally similar across age groups and across the approved epilepsy indications. Safety results in paediatric patients in placebo-controlled clinical studies were consistent with the safety profile of levetiracetam in adults except for behavioural and psychiatric adverse reactions which were more common in children than in adults. In children and adolescents aged 4 to 16 years, vomiting (very common, 11.2%), agitation (common, 3.4%), mood swings (common, 2.1%), affect lability (common, 1.7%), aggression (common, 8.2%), abnormal behaviour (common, 5.6%), and lethargy (common, 3.9%) were reported more frequently than in other age ranges or in the overall safety profile. In infants and children aged 1 month to less than 4 years, irritability (very common, 11.7%) and coordination abnormal (common, 3.3%) were reported more frequently than in other age groups or in the overall safety profile.
A double-blind, placebo-controlled pediatric safety study with a non-inferiority design has assessed the cognitive and neuropsychological effects of Levetiracetam in children 4 to 16 years of age with partial onset seizures. It was concluded that Levetiracetam was not different (non inferior) from placebo with regard to the change from baseline of the Leiter-R Attention and Memory, Memory Screen Composite score in the per-protocol population. Results related to behavioral and emotional functioning indicated a worsening in Levetiracetam treated patients on aggressive behavior as measured in a standardized and systematic way using a validated instrument (CBCL Achenbach Child Behavior Checklist). However subjects, who took Levetiracetam in the long-term open label follow-up study, did not experience a worsening, on average, in their behavioral and emotional functioning; in particular measures of aggressive behaviour were not worse than baseline.
Ivetra IV: The following adverse reactions are discussed in more details in the Precautions section. (see Precautions.) Behavioral Abnormalities and Psychotic Symptoms, Somnolence and Fatigue, Serious Dermatological Reactions, Coordination Difficulties, Hematologic Abnormalities, Increase in Blood Pressure.