Lecetam Oral Solution

Levetiracetam.

Each 1.0 mL contains Levetiracetam 100 mg.

Pharmacology: Pharmacodynamics: The precise mechanism by which levetiracetam exerts its antilepileptic effect is unknown. However, several studies have suggested the mechanism may involve one or more of the following central pharmacologic effects; inhibition of voltage-dependent N-type calcium channels; facilitation of GABA-ergic inhibitory transmission through displacement of negative modulators, reduction of delayed rectifier potassium current; and/or binding to synaptic proteins which modulate neurotransmitter release.
Pharmacokinetics: Absorption: Oral: Rapid and almost complete.
Distribution: V_d: Similar to total body water.
Protein binding: <10%.
Metabolism: Not extensive, primarily by enzymatic hydrolysis; forms metabolites (inactive).
Bioavailability: 100%.
Half-life elimination: Infants and Children < 4 years: 5.3 ± 1.3 hours.
Children 4 to 12 years: 6 ± 1.1 hours.
Adults: 6 - 8 hours.
Time to peak, plasma: Fasting infants and children < 4 years: 1.4 ± 0.9 hours.
Excretion: Urine (66% as unchanged drug and 27% as inactive metabolites).

Levetiracetam is indicated as monotherapy in the treatment of partial onset seizures with or without secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed epilepsy.
Levetiracetam is indicated as adjunctive therapy in the treatment of: partial onset seizures with or without secondary generalisation in adults, adolescents and children from 4 years of age with epilepsy; myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy; primary generalized tonic-clonic seizures in adults, adolescents and children from 6 years of age with idiopathic generalised epilepsy.

Mode of Administration and Recommended Dose: Oral administration.
Levetiracetam oral solution is the preferred formulation for use in children under the age of 6 years. For children from 6 years of age and above, levetiracetam oral solution should be used for doses under 250 mg, for doses that are not multiple of 250 mg when dosing recommendation is not achievable by taking multiple for tablets and for patients unable to swallow tablets.
Monotherapy: The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after 2 weeks. The dose can be further increased by 250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1,500 mg twice daily.
Partial onset seizures: Children and Adolescents 4 to < 16 years: Initial: 10 mg/kg/dose twice daily; increase every 2 weeks by 10 mg/kg/dose to a recommended dose of 30 mg/kg/dose twice daily (maximum daily dose: 3,000 mg/day).
Adolescents ≥ 16 years and Adults: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose to the maximum recommended dose of 1,500 mg twice daily.
Efficacy of doses other than 3,000 mg/day has not been established.
Myoclonic seizures: Children ≥ 12 years, Adolescents, and Adults: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose to the recommended dose of 1,500 mg twice daily.
Efficacy of doses other than 3,000 mg/day has not been established.
Tonic-clonic seizures: Children and Adolescents 6 to < 16 years: Initial: 10 mg/kg/dose twice daily; increase every 2 weeks by 10 mg/kg/dose to a recommended dose of 30 mg/kg/dose twice daily.
Efficacy of doses other than 60 mg/kg/day has not been established.
Adolescents ≥ 16 years and Adults: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose to the recommended dose of 1,500 mg twice daily.
Efficacy of doses other than 1,500 mg twice daily has not been established. (See Tables 1 and 2.)

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Click on icon to see table/diagram/image

Dosing adjustment in renal impairment: Cl_Cr > 80 ml/min/1.73 m²: 500-1500 mg every 12 hours.
Cl_Cr 50-79 ml/min/1.73 m²: 500-1000 mg every 12 hours.
Cl_Cr 30-49 ml/min/1.73 m²: 250-750 mg every 12 hours.
Cl_Cr < 30 ml/min/1.73 m²: 250-500 mg every 12 hours.
End-stage renal disease requiring hemodialysis: 500-1000 mg every 24 hours; supplemental dose of 250 to 500 mg is recommended posthemodialysis.
Dosing adjustment in hepatic impairment: Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Reduce maintenance dose by 50% in patients who also have Cl_Cr < 60 ml/min/1.73 m².

Symptoms of overdose including aggression, agitation, incoordination, coma, unconsciousness, depression, respiratory depression, and somnolence.
Treatment is symptomatic and supportive. Hemodialysis has been reported to result in clearance of levetiracetam (clearance is ~ 50% in 4 hours).

Hypersensitivity to levetiracetam or any component of the formulation.

Based on the Ministry of public Health announcement: This medicine may cause drowsiness therefore should not drive or operate machinery and should not drink alcohol or anything that is mixed with alcohol while using this medicine.
This medicine may cause abnormalities of blood cell.
This medicine is contraindicated in pregnancy because it may cause teratogenic effects on the fetus.
This medicine should be used with caution in hepatic and renal disease.

Antiepileptics are associated with an increased risk of suicidal behavior/thoughts with use (regardless of use); patients should be monitored for signs/symptoms of depression, suicidal tendencies, and other unusual behavior changes during therapy.
Psychosis, hallucination, and behavioral symptoms (including aggression, anger, anxiety, depersonalization, depression, and personality disorder) may occur; incidence may be increased in children. Dose reduction may be required.
Levetiracetam should be withdrawn gradually, when possible, to minimize the potential of increased seizure frequency.
Use caution with renal impairment; dosage adjustment may be necessary.
May cause CNS depression (weakness, dizziness, and somnolence) during the first month of therapy.
Decreases in red blood cell counts, haemoglobin, haematocrit, white blood cell counts and neutrophil have been observed. Case of eosinophilia, agranulocytosis, and lymphocytosis have also been reported.
Efficacy and safety of this drug in children < 4 years (oral) or < 16 years (intravenous) have not been established.

Pregnancy risk factor C.
Animal studies have shown an adverse effect and there are no adequate and well controlled studies in pregnant women.
This drug is excreted in human breast milk. Therefore, a decision should be made whether to discontinue nursing or to discontinue the drug. Taking into account the importance of treatment to the mother.

Cardiovascular: Increased blood pressure (diastolic; infants and children).
Central nervous system: Aggressive behavior (children and adolescents), agitation (children and adolescents), amnesia, anxiety, ataxia (partial onset seizures; includes abnormal gait, incoordination) behavioral problems (includes aggression, agitation, anger, anxiety, apathy, depersonalization, emotional lability, irritability, neurosis), confusion, depression, dizziness, drowsiness, emotional lability, falling (children and adolescents), fatigue, headache, hostility, insomnia (children and adolescents), irritability (infants, children, and adolescents), lethargy (children and adolescents), mood changes (children and adolescents), nervousness, pain, paranoia (children and adolescents), paresthesia, psychotic symptoms, sedation (children and adolescents), vertigo.
Gastrointestinal: Anorexia, constipation (children and adolescents), decreased appetite (children and adolescents), diarrhea, gastroenteritis (children and adolescents), nausea, upper abdominal pain (children and adolescents), vomiting (children and adolescents).
Hematologic & oncologic: Bruise (children and adolescents), decreased neutrophils, decreased white blood cell count, eosinophilia (children and adolescents).
Infection: Infection, influenza.
Neuromuscular & skeletal: Arthralgia (children and adolescents), joint sprain (children and adolescents), neck pain, weakness.
Ophthalmic: Conjunctivitis (children and adolescents), diplopia.
Otic: Otalgia (children and adolescents).
Respiratory: Cough, nasal congestion (children and adolescents), nasopharyngitis, pharyngolaryngeal pain (children and adolescents), pharyngitis, rhinitis, sinusitis.
Miscellaneous: Head trauma.
Rare but important or life-threatening: Abnormal hepatic function tests, acute renal failure, agranulocytosis, alopecia, blurred vision, choreoathetosis, decreased hematocrit, decreased hemoglobin, decreased red blood cells, disturbance in attention, DRESS syndrome, dyskinesia, eczema, equilibrium disturbance, erythema multiforme, hepatic failure, hepatitis, hyperkinesia, hyponatremia, leukopenia, memory impairment, myalgia, myasthenia, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression in some cases), panic attack, personality disorder, pruritus, psychosis, skin rash, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies, thrombocytopenia, toxic epidermal necrolysis, weight loss.

CNS depressants may increase side effects or toxicity of levetiracetam.
No data on the interaction of levetiracetam with alcohol are available.
Food slightly reduced the rate of absorption, but the extent of absorption was not altered.

Store below 30°C.

Anticonvulsants

N03AX14 - levetiracetam ; Belongs to the class of other antiepileptics.

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