Levit

Levit 500 mg is a dull-yellow to gold-yellow film-coated tablet, oval-shaped, biconvex, plain on one side and bisected on the other side.
Each film-coated tablet contains: Levetiracetam 500 mg.
Levetiracetam is an analogue of Piracetam. Levetiracetam acts on the CNS and has been described as a 'nootropic'; it is said to protect the cerebral cortex against hypoxia. It is also reported to inhibit platelet aggregation and reduce blood viscosity at high doses.

Pharmacology: Pharmacodynamics: The active substance, levetiracetam, is a pyrrolidone derivative (S-enantiomer of a-ethyl-2-oxo-1-pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substance.
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 B-carbolines. Furthermore, levetiracetam has been shown 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.
Pharmacokinetics: Levetiracetam is readily absorbed from the gastrointestinal tract and peak plasma concentration are usually achieved within 1.3 hours of oral administration and steady-state achieved after 2 days. Levetiracetam is not extensively metabolized; approximately 25% of the dose is metabolized by hydroxylation to inactive metabolites. About 95% of a dose is excreted as unchanged drug and metabolites in the urine. Plasma protein binding is minimal. The plasma elimination half-life has been reported to be about 7 hours.

Used as an adjunctive therapy in the treatment of partial seizures with or without secondary generalization; may also be considered as a second line drug in generalized tonic clonic seizures in myoclonus including juvenile myoclonic epilepsy and for atonic or tonic seizures.

The initial dose of Levetiracetam is 1 g on the first day of treatment in two divided doses. Thereafter, daily dose may be increased in increments of 1 g every 2 to 4 weeks until effective antiepileptic control is achieved, up to a maximum dose of 3 g daily or as prescribed by the physician. As with other antiepileptics, withdrawal of Levetiracetam therapy or transition to or from another type of antiepileptic therapy should be made gradually to avoid precipitating an increase in the frequency of seizures.

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

Levetiracetam is contraindicated in 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 (e.g. in adults and adolescents weighing more than 50 kg: 500 mg decreases twice daily every two or four weeks; In children and adolescents weighing less than 50 kg: dose decreases should not exceed 10 mg/kg twice daily every two weeks).
Renal or hepatic impairment: 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.

Fertility: No impact on fertility was detected in animal studies. No clinical data are available, potential risk for human is unknown.
Pregnancy: Levetiracetam is not recommended during pregnancy and in women of childbearing potential not using contraception unless clearly necessary. 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. As with other antiepileptic medicinal products, physiological changes during pregnancy may affect levetiracetam concentration. Decrease in levetiracetam plasma concentration has been observed during pregnancy. This decrease is more pronounced during the third trimester (up to 60% of baseline concentration before pregnancy). Appropriate clinical management of pregnant women treated with levetiracetam should be ensured. Discontinuation of antiepileptic treatment may result in exacerbation of the disease which could be harmful to the mother and the fetus.
Lactation: 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.

The most commonly reported adverse drug reactions associated with Levetiracetam are somnolence, weakness, and dizziness. Anorexia, diarrhea, dyspepsia, nausea, ataxia, headache, amnesia, depression, emotional liability, insomnia, aggression, nervousness, tremor, vertigo, diplopia, and rash may occur less frequently.

Antiepileptic medicinal products: Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam did not influence the serum concentrations of existing antiepileptic medicinal products (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these antiepileptic medicinal products did not influence the pharmacokinetics of levetiracetam. As in adults, there is no evidence of clinical significant medicinal product interactions in pediatric patients receiving up to 60 mg/kg/day levetiracetam. 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 valproate. However, children taking enzyme-inducing antiepileptic medicinal products, dose adjustment is not required.
Probenecid: Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to inhibit the renal clearance of the primary metabolite but not levetiracetam. Nevertheless, the concentration of this metabolite remains low. It is expected that other medicinal products excreted by active tubular secretion could also reduce the renal clearance of the metabolite. The effect of levetiracetam on other actively secreted medicinal products, e.g. NSAIDs, sulfonamides and methotrexate is unknown.
Oral contraceptives, digoxin and warfarin: Levetiracetam 1g daily did not influence the pharmacokinetics of oral contraceptives (ethinyl-estradiol and levonorgestrel); endocrine parameters (luteinizing hormone and progesterone) were not modified. Levetiracetam 2g daily did not influence the pharmacokinetics of digoxin and warfarin; prothrombin times were not modified. Co-administration with digoxin, oral contraceptives and warfarin did not influence the pharmacokinetics of levetiracetam.
Antacids: No data on the influence of antacids on the absorption of levetiracetam are available.
Food and alcohol: The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced. No data on the interaction of levetiracetam with alcohol are available.

Store at temperatures not exceeding 30°C.

Anticonvulsants

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

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