Levetiracetam Altan 100 mg/ml

/ Propharm

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 by 250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg twice daily.
Add-on therapy for adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg 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 increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decreases every two to four weeks.
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 (e.g. in adults and adolescents weighing more than 50 kg: 500 mg decreases twice daily every two to four weeks; in children and adolescents weighing less than 50 kg: dose decrease should not exceed 10 mg/kg twice daily every two weeks).
Conversion to or from oral to intravenous administration can be done directly without titration.
Renal impairment
Adjustment of the dose is recommended.
See prescribing information for full details.

Levetiracetam 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.
Levetiracetam as adjunctive therapy:
* in the treatment of partial onset seizures with or without secondary generalization in adults, adolescents patients 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.

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

Renal 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.
Blood cell counts
Rare cases of decreased blood cell count (neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia) 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, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including levetiracetam).
Abnormal and aggressive behaviours
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 adaptation or gradual discontinuation should be considered.
Worsening of seizures
As with other types of antiepileptic drugs, levetiracetam may rarely exacerbate seizure frequency or severity. This paradoxical effect was mostly reported within the first month after levetiracetam initiation or increase of the dose, and was reversible upon drug discontinuation or dose decrease.
See prescribing information for full details.

Very common: Nasopharyngitis, Somnolence, Headache.
Common: Anorexia, Depression, Hostility/Aggression, Anxiety, Insomnia, Nervousness/Irritability, Convulsion, Balance disorder, Dizziness, lethargy,
Tremor, Vertigo, Cough, Abdominal pain, Diarrhoea, Dyspepsia, Vomiting, Nausea, Rash, Asthenia/fatigue.
See prescribing information for full details.

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 of levetiracetam. Nevertheless, the concentration of this metabolite remains low.
Methotrexate
Concomitant administration of levetiracetam and methotrexate has been reported to decrease methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients treated concomitantly with the two drugs.
See prescribing information for full details.

Pregnancy: A large amount of post-marketing data on pregnant women exposed to levetiracetam monotherapy (more than 1800, among which in more than 1500 exposure occurred during the 1st trimester) do not suggest an increase in the risk for major congenital malformations.
limited evidence is available on the neurodevelopment of children exposed to Levetiracetam monotherapy in utero. Data from two observational population-based registry studies undertaken in largely the same dataset from the Nordic countries and including more than 1000 children born to women with epilepsy prenatally exposed to levetiracetam monotherapy do not suggest an increased risk of autism spectrum disorders orintellectual disability compared to children born to women with epilepsy not exposed to an antiepileptic drug in utero. The mean follow-up time of children in the levetiracetam group was shorter than for the group of children non exposed to any antiepileptic drug (e.g. 4.4 years vs 6.8 years in one of the studies).
Levetiracetam can be used during pregnancy, if after careful assessment it is considered clinically needed. In such case, the lowest effective dose is recommended.
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 (up to 60% of baseline concentration before pregnancy). Appropriate clinical management of pregnant women treated with levetiracetam should be ensured.
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.

Symptoms
Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed.
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.