Each film coated tablet contains: Levetiracetam 500 mg.
Levetiracetam is a white to off-white powder with a faint odour and a bitter taste. It is very soluble in water (104 g/100mL). It is freely soluble in chloroform (65.3 mg/100mL) and in methanol (53.6 g/100 mL), soluble in ethanol (16.5 g/100mL), sparingly soluble in acetonitrile (5.7 g/100mL) and practically insoluble in n-hexane.
Excipients/Inactive Ingredients: Colours: Yellow Oxide of Iron & Titanium Dioxide.
Pharmacology: Pharmacological Effects and Mechanism of Action: Levetiracetam exhibits a novel pharmacological profile insofar as it inhibits partial and secondarily generalized tonic-clonic seizures in the kindling model, yet is ineffective against maximum electroshock- and pentylenetetrazol induced seizures, findings consistent with clinical effectiveness against partial and secondarily generalized tonic-clonic seizures. The mechanism by which levetiracetam exerts these antiseizure effects is unknown. No evidence for an action on voltage-gated Na+ channels or either GABA- or glutamate-mediated synaptic transmission has emerged. A stereoselective binding site has been identified in rat brain membranes and the synaptic vesicle protein SVZA has been shown to be a brain-binding target of levetiracetam.
Pharmacokinetics: Levetiracetam is readily absorbed from the gastrointestinal tract with a bioavailability of almost 100%; peak plasma concentrations are usually achieved within 1.3 hours of oral doses and steady state achieved after 2 days. Plasma protein binding is minimal at less than 10%. Levetiracetam is not extensively metabolised; about 25% of a dose is metabolised by hydroxylation to inactive metabolites. Around 95% of a dose is excreted as unchanged drug in the urine.
The plasma elimination half-life has been reported to be about 7 hours in adults and children aged 12 years and over, the half-life may be shorter in younger children.
Levetiracetam is distributed into breast milk.
Seizures disorders: Partial Seizure, Myoclonic Seizure, Primary Generalized Tonic-Clonic.
RECOMMENDED DOSE: Monotherapy of focal seizures with or without secondary generalisation, by mouth or intravenous infusion, ADULT and CHILD over 16 years, initially 250 mg once daily increased after 1-2 weeks to 250 mg twice daily; thereafter, increased according to response in steps of 250 mg twice daily every 2 weeks; max. 1.5 g twice daily.
Adjunctive therapy of focal seizures with or without secondary generalisation, by mouth, ADULT and CHILD over 12 years, body-weight over 50 kg, initially 250 mg twice daily, adjusted in steps of 500 mg twice daily every 2-4 weeks; max. 1.5 g twice daily; CHILD over 6 months, body-weight under 50 kg, initially 10 mg/kg once daily, adjusted in steps not exceeding 10 mg/kg twice daily every 2 weeks; max 30 mg/kg twice daily; CHILD 1-6 months, initially 7 mg/kg once daily, adjusted in steps not exceeding 7 mg/kg twice daily every 2 weeks; max 21 mg/kg twice daily.
Adjunctive therapy of myoclonic seizures and tonic-clonic seizures, by mouth or by intravenous infusion, ADULT and CHILD over 12 years, body-weight over 50 kg, initially 250 mg twice daily, adjusted in steps of 500 mg twice daily every 2-4 weeks; max. 1.5 g twice daily; CHILD 12-18 years, body-weight under 50 kg, initially 10 mg/kg once daily, adjusted in steps not exceeding 10 mg/kg twice daily every 2 weeks; max 30 mg/kg twice daily.
MODE OF ADMINISTRATION: Levetiracetam is given orally with or without food.
A 38-year old woman who ingested 30 g of levetiracetam vomited 4 hours later and presented with hypoxia, hypotension, and respiratory depression 6 hours after ingestion; peak plasma levetiracetam concentration was 400 micrograms/mL. The patient recovered without sequelae over 48 hours with symptomatic treatment.
Oral administered levetiracetam is contraindicated in patients with known hypersensitivity to the drug or any ingredients in the formulation.
Nervous System Effects: Adverse neuropsychiatric effects reported during levetiracetam treatment are classified into 3 categories: somnolence and fatigue, coordination difficulties, and behavioral abnormalities.
Somnolence, asthenia and coordination difficulties occurred most frequently within 4 weeks of treatment. Psychotic manifestations and hallucinations were reported rarely in patients receiving levetiracetam in clinical studies. Other behavioral symptoms (eg., agitation, hostility, anxiety, apathy, emotional liability, depersonalization, depression, aggression, anger, irritability) accorded in 13.3% of levetiracetam-treated patients in clinical studies compared with 6.2% of placebo patients, and 1.7% of levetiracetam-treated patients discontinued treatment because of these events.
Suicidality Risk: US FDA has altered healthcare professional about an increased risk of suicidality (Suicidal behavior or ideation in an analysis of studies using various anticonvulsants, including levetiracetam, compared with placebo.
Discontinuance of Levetiracetam: Because of the possibility of increased seizure frequency, anticonvulsant drugs, including levetiracetam, should not be discontinued suddenly. Oral levetiracetam should be withdrawn gradually by reducing the dosage by 1 g daily at 2-week intervals.
General Precautions: Minor decrease in total mean erythrocyte count, mean hemoglobin, and mean hematocrit have been reported. Leukopenia, neutropenia, pancytopenia (with myelosuppression in same cases), and thrombocytopenia also have been observed, although a causal relationship to the drug has on been established.
Hepatic Effects: No meaningful changes in mean liver function test results reporting controlled studies in adult patients.
Women of child-bearing potential should discuss the impact of both epilepsy and the treatment of epilepsy on the outcome of pregnancy with a specialist.
There is an increased risk of teratogenicity associated with the use of antiepileptic drugs (especially if used during the first trimester and if the patient takes two or more antiepileptic drugs). There is not enough evidence to establish the risk of teratogenicity with other antiepileptic drugs. Women of childbearing potential who take antiepileptic drugs should be given contraceptive advice. Some antiepileptic drugs can reduce the efficacy of hormonal contraceptives and the efficacy of some antiepileptics may be affected by hormonal contraceptives.
To reduce the risk of neural tube defects, folate supplementation is advised before conception and throughout the first semester.
The concentration of antiepileptic drugs in the plasma can change during pregnancy, particularly in the later stages. Additionally, in patients taking topiramate or levetiracetam, it is recommended that fetal growth should be monitored.
Women who have seizures in the second half of pregnancy should be assessed for eclampsia before any change is made to antiepileptic treatment.
Withdrawal effects in the newborn may occur with some antiepileptic drugs, in particular benzodiazepines and phenobarbital.
Breast-feeding: Breast-feeding is acceptable with all antiepileptic drugs taken in normal doses, with the possible exception of the barbiturates and some of the newer antiepileptics.
Adverse effects occurring in 1% or more of patients receiving oral levetiracetam and more frequently than placebo include somnolence, asthenia, headache, infection, dizziness, pain, pharyngitis, depression, nervousness, rhinitis, anorexia, ataxia, vertigo, amnesia, anxiety, emotional liability, hostility, paresthesia, increased cough, sinusitis, and diplopia and were reported in clinical studies in which levetiracetam was administered in conjunction with other anticonvulsants. Asthesia, somnolence, and dizziness occurred predominantly during the initial 4 weeks of treatment.
Drug Affecting Hepatic Microsomal Enzymes: Pharmacokinetic interaction unlikely.
Anticonvulsants: Clinically important pharmacokinetic interaction unlikely with anticonvulsants (eg., carbamazepine, gabapentin, lamotrigine, Phenobarbital, phenytoin, primidone, valproic acid).
Probenecid: Potential pharmacokinetic interaction. No effects on levetiracetam pharmacokinetic, but steady-state plasma concentrations of principal inactive metabolite were approximately doubled due to 60% reduction in renal clearance; clinically unimportant.
Oral Contraceptives: Pharmacokinetic interaction unlikely.
Digoxin: Pharmacokinetic interaction unlikely.
Warfarin: Pharmacokinetic interaction unlikely.
Protein-bound Drugs: Pharmacokinetic interaction unlikely.
N03AX14 - levetiracetam ; Belongs to the class of other antiepileptics.
FC tab 500 mg x 6 x 10's.