JULITAM 500 Levetiracetam 500mg Film-Coated Tablet 1's

For monotherapy and adjunctive treatment of partial seizures with or without secondary generalization and for adjunctive therapy of myoclonic seizures and primarily generalized tonic clonic seizures.

Adults 16 years and older: 1 g/day initial daily dose in two divided doses (500 mg twice daily) thereafter the daily dose may be increased in steps of 1 g every 2 to 4 weeks until effective antiepileptic control is achieved up to a maximum dose of 3 g daily.
Children: Less than 50 kg weight 20 mg/kg daily may be increased in steps of 20 mg/kg every weeks to a maximum of 60 mg/kg daily.
More than 50 kg weight may be given the adult dose (see previously).
As monotherapy: 500 mg daily increased after 2 weeks to 1 g daily. Further increases may be made in steps of 500 mg every 2 weeks up to maximum of 3 g daily.

Symptoms: Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Levetiracetam overdoses.
Management of overdose: After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. There is no specific antidote for levetiracetam. Treatment of an overdose will be symptomatic and may include haemodialysis. The dialyser extraction efficiency is 60% for levetiracetam and 74% for the primary metabolite.

May be taken with or without food.

Hypersensitivity to the active substance or other pyrrolidone derivatives or to any of the excipients.

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.
Use in Children: 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.

Pregnancy: There are no adequate data available from the use of Levetiracetam in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for human is unknown.
Levetiracetam is not recommended during pregnancy and in women of childbearing potential not using contraception unless clearly necessary.
As with other antiepileptic medicinal products, physiological changes during pregnancy may affect levetiracetam concentration. Decrease in levetiracetam plasma concentrations has been observed during pregnancy. This decrease is more pronounced during the third trimester. Appropriate clinical management of pregnant women treated with levetiracetam should be ensured. Discontinuation of antiepileptic treatments may result in exacerbation of the disease which could be harmful to the mother and the foetus.
Breastfeeding: Levetiracetam is excreted in human breast milk. Therefore, breastfeeding is not recommended. However, if levetiracetam treatment is needed during breastfeeding, the benefit/risk of the treatment should be weighed considering the importance of breastfeeding.
Fertility: No impact on fertility was detected in animal studies. No clinical data are available, potential risk for human is unknown.

Adverse effects reported in clinical studies and from post marketing survey are listed followings: CNS: Somnolence (23%); headache (14%); hostility (12%); fatigue, nervousness (10%); dizziness (9%); personality disorder (8%); agitation, emotional lability, irritability (6%); depression, mood swings, vertigo (5%); ataxia, seizures (3%); amnesia, anxiety, confusion, hypersomnia, increased reflexes, insomnia, irritability, paresthesia (2%); suicidal behavior.
Dermatologic: Pruritus, skin discoloration, vesiculobullous rash (2%); alopecia.
ENT: Nasopharyngitis (14%); rhinitis (13%); pharyngitis (10%); conjunctivitis (3%); amblyopia, diplopia, ear pain (2%).
GI: Vomiting (15%); anorexia (13%); diarrhea (8%); gastroenteritis (4%); constipation (3%); pancreatitis.
Genitourinary: Albuminuria (4%); urine abnormality (2%).
Hematologic-Lymphatic: Ecchymosis (4%); leukopenia, neutropenia, pancytopenia, thrombocytopenia.
Hepatic: Hepatic failure, hepatitis.
Metabolic-Nutritional: Dehydration (2%); weight loss.
Musculoskeletal: Neck pain (8%).
Respiratory: Increased cough (11%); asthma, sinusitis (2%).
Miscellaneous: Accidental injury (17%); asthenia (15%); infection (13%); pain (7%); influenza (5%); flu syndrome (3%); face edema, viral infection (2%).

Store at temperatures not exceeding 30°C.

Pharmacology: Mechanism of Action: The mechanism of action of levetiracetam still remains to be fully elucidated but appears to be different from the mechanisms of current antiepileptic medicinal products. In vitro and in vivo experiments suggest that levetiracetam does not alter basic cell characteristics and normal neurotransmission.
In vitro studies show that levetiracetam affects intraneuronal Ca²⁺ levels by partial inhibition of N-type Ca²⁺ currents and by reducing the release of Ca²⁺ from intraneuronal stores. In addition, it partially reverses the reductions in GABA- and glycine-gated currents induced by zinc and β-carbolines. Furthermore, levetiracetam has been shown in in vitro studies to bind to a specific site in rodent brain tissue. This binding site is the synaptic vesicle protein 2A, believed to be involved in vesicle fusion and neurotransmitter exocytosis. Levetiracetam and related analogs show a rank order of affinity for binding to the synaptic vesicle protein 2A which correlates with the potency of their anti-seizure protection in the mouse audiogenic model of epilepsy. This finding suggests that the interaction between levetiracetam and the synaptic vesicle protein 2A seems to contribute to the antiepileptic mechanism of action of the medicinal product.
Pharmacodynamics: Levetiracetam induces seizure protection in a broad range of animal models of partial and primary generalised seizures without having a pro-convulsant effect. The primary metabolite is inactive. In man, an activity in both partial and generalised epilepsy conditions has confirmed the broad spectrum pharmacological profile of levetiracetam.
Clinical efficacy and safety: Adjunctive therapy in the treatment of partial onset seizures with or without secondary generalisation in adults, adolescents, children and infants from 1 month of age with epilepsy.
In adults, levetiracetam efficacy has been demonstrated in 3 double-blind, placebo-controlled studies at 1000 mg, 2000 mg, or 3000 mg/day, given in 2 divided doses, with a treatment duration of up to 18 weeks. In a pooled analysis, the percentage of patients who achieved 50% or greater reduction from baseline in the partial onset seizure frequency per week at stable dose (12/14 weeks) was of 27.7%, 31.6% and 41.3% for patients on 1000, 2000 or 3000mg levetiracetam respectively and of 12.6% for patients on placebo.
Pharmacokinetics: Levetiracetam is readily absorbed from the gastrointestinal tract with a bioavailability of almost 100%; peak plasma concentration usually occur within 1.3 hours of oral doses and steady state after 2 days. Plasma protein binding is minimal at less than 10%. Levetiracetam is not extensively metabolized; about 25% of a dose is metabolized by hydroxylation to inactive metabolites. Around 95% of a dose is excreted as unchanged drug and metabolites 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.

Anticonvulsants