Composition:
Each 1ml Solution contains 100mg levetiracetam.

Pharmacodynamic properties :
The mechanism of action of levetiracetam still remains to be fully elucidated. Experiments suggest that levetiracetam does not alter basic cell characteristics and normal neurotransmission.

Pharmacokinetics:

• Distribution:
• Neither levetiracetam nor its primary metabolite are significantly bound to plasma proteins (< 10 %). The volume of distribution of levetiracetam is approximately 0.5 to 0.7 l/kg, a value close to the total body water volume.
• Elimination:
• The plasma half-life in adults was 7 ± 1 hours and did not vary either with dose, route of administration or repeated administration. The mean total body clearance was 0.96 ml/min/kg.
• 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.

Indications:
1-Levetram 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.
2. Levetram is indicated as adjunctive therapy in the:
A. Treatment of partial onset seizures with or without secondary generalisation in adults, adolescents and children from 4 years of age with epilepsy.
B-Treatment of myoclonic seizures in adults and adolescents from 12 years of  age with Juvenile Myoclonic Epilepsy.
C-Treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.
3-Levetram concentrate is an alternative for patients when oral administration is temporarily not feasible.

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

Dosage & Method of administration:
1- Monotherapy for adults and adolescents from 16 years of age: The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1,500 mg twice daily.
2- Add-on therapy for adults (≥18years) and adolescents (12to17 years)weighing 50kg or more: The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. Depending upon the clinical response and tolerability, the daily dose can be increasedup to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily
increases or decreases every two to four weeks.
Method of administration :
Desitrend concentrate is for intravenous use only and the recommended dose must be diluted in at least 100 ml of acompatible diluent and administered intravenously as a 15-minute intravenous infusion.
Levetracitam mixed with the following diluents:
-  Sodium chloride 9 mg/ml (0.9%) solution for injection.
-  Lactated Ringer's solution for injection.
-  Glucose 50 mg/ml (5%) solution for injection.
Preparation and administration of levetiracetam concentrate for solution for infusion:

Duration of treatment:
There is no experience with administration of intravenous levetiracetam for longer period than 4 days.
Discontinuation: If levetiracetam has to be discontinued it is recommended to withdraw it gradually.
Elderly (65 years and older)Adjustment of the dose is recommended in elderly patients With  compromised renal function.
Renal impairment :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,using the following formula:

Then CLcr is adjusted for body surface area (BSA) as follows:
​
Dosing adjustment for adult and adolescent patients weighing more than 50 kg with impaired
renal function:

	Creatinine    clearance (ml/min/1.73m2)	Dose and frequency Children from 4 years and adolescents weighing less than50 kg
Normal	> 80	10 to 30 mg/kg (0.10 to 0.30 ml/kg) twice daily
Mild	50 - 79	10 to 20 mg/kg (0.10 to 0.20 ml/kg) twice daily
Moderate	30 - 49	5 to 15 mg/kg (0.05 to 0.15 ml/kg) twice daily
Severe	< 30	5 to 10 mg/kg (0.05 to 0.10 ml/kg) twice daily
End-stage renal disease patients undergoing dialysis	---	10 to 20 mg/kg (0.10 to 0.20 ml/kg) once daily

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 < 60 ml/min/1.73 m2.
Paediatric population :The physician should prescribe the most appropriate pharmaceutical form, Presentation and strength according to age, weight and dose. Monotherapy .The safety and efficacy of Desitrend in children and adolescents below 16 years as monotherapy treatment have not been established. No data are available.
Add-on therapy for children aged 4 to 11 years and adolescents (12 to 17 years) weighing less than 50 kg .
The initial therapeutic dose is 10 mg/kg twice daily. Depending upon the clinical response and tolerability,the dose can be increased up to 30 mg/kg twice daily. Dose changes should not exceed increases or decreases of 10 mg/kg twice daily every two weeks. The lowest effective dose should be used. Dose in children 50 kg or greater is the same as in adults.
Dose recommendations for children and adolescents:

Weight	Starting dose: mg/kg twice daily	Maximum dose: 30 mg/kg twice daily
15 kg (1)	150 mg twice daily	450 mg twice daily
20 kg (1)	200 mg twice daily	600 mg twice daily
25 kg	250 mg twice daily	750 mg twice daily
From 50 kg (2)	500 mg twice daily	1,500 mg twice daily

 

 

 

 

 

 

 

 

(1) Children 25 kg or less should preferably start the treatment with Desitrend 100 mg/ml oral solution.
(2) Dose in children and adolescents 50 kg or more is the same as in adults.
Add-on therapy for infants and children less than 4 years:
The safety and efficacy of Desitrend concentrate for solution for infusion in infants and children less than 4 years have not been established.

Overdose:
Symptoms:
Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma.
Management of overdose:
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.

Side effects:
Very common: Nasopharyngitis, Somnolence and headache.
Common: Anorexia, Depression, aggression, anxiety, insomnia, nervousness, convulsion, balance disorder, dizziness, lethargy, tremor, cough, dizziness, abdominal pain, diarrhoea, dyspepsia, vomiting, nausea, rash and fatigue.

Precautions:

• 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 befor dose selection.
• Rare cases of decreased blood cell counts have been described in association with
•  Levetiracetam administration, generally at the beginning of the treatment. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
• Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients
•  treated with anti-epileptic agents. Therefore, patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered.
• Levetiracetam may cause psychotic symptoms and behavioural abnormalities including

Irritability and aggressiveness. Patients treated with levetiracetam should be monitored for developing  psychiatric signs suggesting important mood and/or personality changes. If such behaviours  are noticed, treatment or adaptation gradual discontinuation should
be considered

Drug Interactions:
1-Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam did not influence the serum concentrations of existing antiepileptic medicinal products.
2-Levetracitam with probenecid, a renal tubular secretion blocking agent, has been shown To inhibit the renal clearance of the primary metabolite, but not of levetiracetam.
3- Concomitant administration of levetiracetam and methotrexate has been reported to Decrease methotrexate clearance, resulting in increased blood methotrexate concentration to potentially toxic levels
4-Levetiracetam did not influence the pharmacokinetics of oral contraceptives, endocrine parameters were not modified. digoxin and warfarin; prothrombin. Coadministration with digoxin, oral contraceptives and warfarin did not influence the pharmacokinetics of
levetiracetam.

Effects on ability to drive and use machines:
Levetiracetam has minor or moderate influence on the 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, some patients might experience somnolence or other central nervous system.

Use during Pregnancy or lactation:
-Levetiracetam can be used with caution during pregnancy after careful assessment it is considered clinically needed. In such case, the lowest effective dose is recommended.
- Levetiracetam is excreted in human breast milk. Therefore, breast-feeding is not recommended.