COMPOSITION:
Each film coated tablet contains 250 or 500 mg Levetiracetam.
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. The experiments suggest that levetiracetam does not alter basic cell characteristics and normal neurotransmission.
Studies show that levetiracetam affects intraneuronal Ca+2 levels by partial inhibition of N-type Ca+2 currents and by reducing the release of Ca+2 from intraneuronal stores. In addition it partially reverses the reductions in GABA- and glycine-gated currents induced by zinc and β carbolines.
INDICATIONS:
Levetiracetam Domina is indicated as a monotherapy in the treatment of partial onset seizures with or without secondary generalization in patients from 16 years of age with newly diagnosed epilepsy.
Levetiracetam Domina is indicated as adjunctive therapy
- In treatment of partial onset seizures with or without secondary generalization in adults and children from 4 years of age with epilepsy.
- In the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic epilepsy.
- In the treatment of primary generalized tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalized epilepsy.
DOSAGE:
The film coated tablets must be taken orally, swallowed with a sufficient quantity of liquid and may be taken with or without food. The daily dose is administered in two equally divided doses.
- Monotherapy:
Adults and adolescents from 16 years of age:
The recommended starting dose is 250mg twice daily which should be increased to an initial therapeutic dose of 500mg twice daily after two weeks. The dose can be further increased by 250mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500mg twice daily.
- Add-on therapy:
Children aged 4 to 11 years and adolescents (12 to 17 years) weighing less than 50kg:
The initial therapeutic dose is 10mg/kg twice daily.
Depending upon the clinical response and tolerability, the dose can be increased up to 30mg/kg twice daily. Dose changes should not exceed increases or decreases of 10mg/kg twice daily every two weeks. The lowest effective dose should be used.
Dosage in children 50kg or greater is the same as in adults.
Adults (≥18 years) and adolescents (12 to 17 years) weighing 50kg or more:
The initial therapeutic dose is 500mg twice daily.
Depending upon the clinical response and tolerability, the daily dose can be increased up to 1500mg twice daily. Dose changes can be made in 500mg twice daily increases or decreases every two to four weeks.
Elderly (65 years and older):
Adjustment to the dose is recommended in elderly patients with compromised renal function.
Patients with renal impairment:
The daily dose must be individualized according to renal function.
|
Group |
Creatinine clearance (ml/min) |
Dosage and frequency |
|
Normal |
> 80 |
500 to 1500mg twice daily |
|
Mild |
50-79 |
500 to 1000mg twice daily |
|
Moderate |
30-49 |
250 to 750mg twice daily |
|
Severe |
< 30 |
250 to 500mg twice daily |
|
End stage renal disease patients undergoing dialysis(1) |
- |
500 to 1000mg once daily(2) |
(1) A 750mg loading dose is recommended on the first day of treatment with Levetiracetam Domina.
(2) Following dialysis, a 250 to 500mg supplemental dose is recommended.
Patients with hepatic impairment:
No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the Creatinine clearance may underestimate the renal insufficiency. Therefore a 50% reduction of the daily maintenance dose is recommended when the Creatinine clearance is < 70ml/min.
SIDE EFFECTS:
The most commonly reported side effects were somnolence, asthenia, fatigue and dizziness.
Common: amnesia, agitation, depression, abnormal behavior, anger, abdominal pain, diarrhea, dyspepsia, nausea, vomiting, vertigo, diplopia and myalgia.
Incidence and severity of the central nervous system related side effects decreased over time.
CONTRAINDICATIONS:
Hypersensitivity to levetiracetam or other pyrrolidone derivatives or any of the excipients.
DRUG INTERACTIONS:
Levetiracetam do 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 do not influence the pharmacokinetic of levetiracetam.
There is no evidence of clinically significant medicinal product interactions in patients receiving levetiracetam.
PRECAUTIONS:
In accordance with current clinical practice, if Levetiracetam Domina has to be discontinued, it is recommended to withdraw it gradually (e.g. in adults: 500mg decreases twice daily every 2 to 4 weeks; in children: dose decrease should not exceed 10mg/kg twice daily every two weeks).
The administration of Levetiracetam Domina 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.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
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 PREGNANCY OR LACTATION:
Levetiracetam Domina should not be used during pregnancy unless clearly necessary. Discontinuation of antiepileptic treatment may result in exacerbation of disease which could be harmful to the mother and the foetus.
Levetiracetam is excreted in human breast milk. Therefore, breast feeding is not recommended.
PHARMACOKINETIC PROPERTIES:
Absorption: Levetiracetam is rapidly absorbed after oral administration. Oral absolute bioavailability is close to 100%.
Peak plasma concentrations (Cmax) are achieved at 1.3 hours after dosing. Steady state is achieved after two days of a twice daily administration schedule.
Distribution: No tissue distribution data are available in humans.
Neither levetiracetam nor its primary metabolite are significantly bound to plasma proteins (< 10%).
Elimination: The plasma half life in adults was 7±1 hours (10-11 hours for elderly because of the decreasing in the renal function in this population) and did not vary either with dose, route of administration or repeated administration.
The major route of excretion was via urine, accounting for a mean 95% of the dose. Excretion via faeces accounted for only 0.3% of the dose.