Source: Medicines Authority (MT) Revision Year: 2022 Publisher: Remedica Ltd, Aharnon Str., Limassol Industrial Estate, 3056 Limassol, Cyprus
Quetra 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.
Quetra is indicated as adjunctive therapy:
The recommended dosing for monotherapy (from 16 years of age) and adjunctive therapy is the same; as outlined below.
The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. However, a lower initial dose of 250 mg twice daily may be given based on physician assessment of seizure reduction versus potential side effects. This can be increased to 500 mg twice daily after two weeks.
Depending upon the clinical response and tolerability, the daily dose can be increased up to 1500 mg twice daily. Dose changes can be made in 250 mg or 500 mg twice daily increases or decreases every two to four weeks.
The physician should prescribe the most appropriate pharmaceutical form, presentation and strength according to weight, age and dose. Refer to Paediatric population section for dosing adjustments based on weight.
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 to four weeks; in infants older than 6 months, children and adolescents weighting less than 50 kg: dose decrease should not exceed 10 mg/kg twice daily every two weeks; in infants (less than 6 months): dose decrease should not exceed 7 mg/kg twice daily every two weeks).
Adjustment of the dose is recommended in elderly patients with compromised renal function (see “Renal impairment” below).
The daily dose must be individualised according to renal function.
For adult patients, refer to the following table and adjust the dose as indicated. To use this dosing table, an estimate of the patient’s creatinine clearance (CLcr) in mL/min is needed. The CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination, for adults and adolescents weighting 50 kg or more, the following formula:
CLcr (mL/min) = [140-age (years)] × weight (kg) / 72 × serum creatinine (mg/dL)
(× 0.85 for women)
Then CLcr is adjusted for body surface area (BSA) as follows:
CLcr (mL/min/1.73 m²) = CLcr (mL/min) / BSA subject (m²)
× 1.73
Dosing adjustment for adult and adolescents patients weighing more than 50 kg with impaired renal function:
| Group | Creatinine clearance (mL/min/1.73m²) | Dose and frequency |
|---|---|---|
| Normal | ≥80 | 500 to 1500 mg twice daily |
| Mild | 50-79 | 500 to 1 000 mg twice daily |
| Moderate | 30-49 | 250 to 750 mg twice daily |
| Severe | <30 | 250 to 500 mg twice daily |
| End-stage renal disease patients undergoing dialysis1 | - | 500 to 1000 mg once daily2 |
1 A 750 mg loading dose is recommended on the first day of treatment with levetiracetam.
2 Following dialysis, a 250 to 500 mg supplemental dose is recommended.
For children with renal impairment, levetiracetam dose needs to be adjusted based on the renal function as levetiracetam clearance is related to renal function. This recommendation is based on a study in adult renally impaired patients.
The CLcr in mL/min/1.73 m² may be estimated from serum creatinine (mg/dL) determination, for young adolescents, children and infants, using the following formula (Schwartz formula):
CLcr (mL/min/1.73 m²) = Height (cm) × ks / Serum Creatinine (mg/dL)
ks = 0.45 in Term infants to 1 year old; ks = 0.55 in Children to less than 13 years and in adolescent female; ks = 0.7 in adolescent male.
Dosing adjustment for infants, children and adolescents patients weighing less than 50 kg with impaired renal function:
| Group | Creatinine clearance (mL/min/1.73m²) | Dose and frequency1 | |
|---|---|---|---|
| Infants 1 to less than 6 months | Infants 6 to 23 months, children and adolescents weighing less than 50 kg | ||
| Normal | ≥80 | 7 to 21 mg/kg (0.07 to 0.21 mL/kg) twice daily | 10 to 30 mg/kg (0.10 to 0.30 mL/kg) twice daily |
| Mild | 50-79 | 7 to 14 mg/kg (0.07 to 0.14 mL/kg) twice daily | 10 to 20 mg/kg (0.10 to 0.20 mL/kg) twice daily |
| Moderate | 30-49 | 3.5 to 10.5 mg/kg (0.035 to 0.105 mL/kg) twice daily | 5 to 15 mg/kg (0.05 to 0.15 mL/kg) twice daily |
| Severe | <30 | 3.5 to 7 mg/kg (0.035 to 0.07 mL/kg) twice daily | 5 to 10 mg/kg (0.05 to 0.10 mL/kg) twice daily |
| End-stage renal disease patients undergoing dialysis | -- | 7 to 14 mg/kg (0.07 to 0.14 mL/kg)once daily 2,4 | 10 to 20 mg/kg (0.10 to 0.20 mL/kg) once daily3,5 |
1 Levetiracetam oral solution should be used for doses under 250 mg, for doses not multiple of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets.
2 A 10.5 mg/kg (0.105 mL/kg) loading dose is recommended on the first day of treatment with levetiracetam.
3 A 15 mg/kg (0.15 mL/kg) loading dose is recommended on the first day of treatment with levetiracetam.
4 Following dialysis, a 3.5 to 7 mg/kg (0.035 to 0.07 mL/kg) supplemental dose is recommended.
5 Following dialysis, a 5 to 10 mg/kg (0.05 to 0.10 mL/kg) supplemental dose is recommended.
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 < 60 ml/min/1.73m².
The physician should prescribe the most appropriate pharmaceutical form, presentation and strength according to age, weight and dose.
The tablet formulation is not adapted for use in infants and children under the age of 6 years. Levetiracetam oral solution is the preferred formulation for use in this population. In addition, the available dose strengths of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases levetiracetam oral solution should be used.
The safety and efficacy of levetiracetam in children and adolescents below 16 years as monotherapy treatment have not been established. No data are available.
Please refer to the above section on Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more.
Levetiracetam oral solution is the preferred formulation for use in infants and children under the age of 6 years.
For children 6 years and above, levetiracetam oral solution should be used for doses under 250 mg, for doses not multiple of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets.
The lowest effective dose should be used for all indications. The starting dose for a child or adolescent of 25 kg should be 250 mg twice daily with a maximum dose of 750 mg twice daily.
Dose in children 50 kg or greater is the same as in adults for all indications.
Please refer to the above section on Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more for all indications.
Dose recommendations for children 6 years and above and adolescents:
| Weight | Starting dose: 10 mg/kg twice daily | Maximum dose: 30 mg/kg twice daily |
|---|---|---|
| Less than 25 kg | Oral solution is the preferred formulation | |
| 25 kg | 250 mg twice daily | 750 mg twice daily |
| From 50 kg* | 500 mg twice daily | 1500 mg twice daily |
* Dose in children and adolescents 50 kg or more is the same as in adults
The film-coated tablets must be taken orally, swallowed with a sufficient quantity of liquid and may be taken with or without food. After oral administration the bitter taste of levetiracetam may be experienced. The daily dose is administered in two equally divided doses.
Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with levetiracetam overdoses.
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.
3 years.
This medicinal product does not require any special storage conditions.
Quetra 250 mg film-coated tablets are packaged in aluminium/PVC-PE-PVDC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 80, 100, 120 and 200 filmcoated tablets.
Quetra 500 mg film-coated tablets are packaged in aluminium/PVC-PE-PVDC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 80, 100, 120 and 200 filmcoated tablets.
Quetra 750 mg film-coated tablets are packaged in aluminium/PVC-PE-PVDC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 80, 100, 120 and 200 filmcoated tablets.
Quetra 1 000 mg film-coated tablets are packaged in aluminium/PVC-PE-PVDC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 80, 100, 120 and 200 film-coated tablets.
Not all pack sizes may be marketed.
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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