Tiralepsy

Name of the medicinal product

• Tiralepsy 250 mg film-coated tablets.
• Tiralepsy 500 mg film-coated tablets.
• Tiralepsy 1000 mg film-coated tablets.

Qualitative and quantitative composition

Film Coated Tablets Tablets:

Each film-coated tablet contains 250 mg Leviteracetam, 500 mg Leviteracetam, or 1000 mg Leviteracetam.

Pharmaceutical form

Film-coated tablet:

Clinical particulars

Therapeutic indications

Tiralepsy 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.

Tiralepsy is indicated as adjunctive therapy

• in the treatment of partial onset seizures with or without secondary generalisation in adults adolescents.
• in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy.
• in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.

Contraindications

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

Interaction with other medicinal products and other forms of interaction

Antiepileptic medicinal products

Tiralepsy 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 Tiralepsy.

A retrospective assessment of pharmacokinetic interactions in children and adolescents with epilepsy (4 to 17 years) confirmed that adjunctive therapy with orally administered Tiralepsy did not influence the steady-state serum concentrations of concomitantly administered carbamazepine and valproate. However, data suggested a 20 % higher Tiralepsy clearance in 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 of Tiralepsy. 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 Tiralepsy on probenecid was not studied and the effect of Tiralepsyon other actively secreted medicinal products, e.g. NSAIDs, sulfonamides and methotrexate, is unknown.

Oral contraceptives and other pharmacokinetics interactions

Tiralepsy1,000 mg daily did not influence the pharmacokinetics of oral contraceptives (ethinyl-estradiol and levonorgestrel); endocrine parameters (luteinizing hormone and progesterone) were not modified. Tiralepsy2,000 mg 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 Tiralepsy.

Antacids

No data on the influence of antacids on the absorption of Tiralepsy are available.

Food and alcohol

The extent of absorption of Tiralepsywas not altered by food, but the rate of absorption was slightly reduced.

No data on the interaction of Tiralepsywith alcohol are available.

Fertility, pregnancy and lactation

Pregnancy

There are no adequate data available from the use of Tiralepsy in pregnant women.

Tiralepsy is not recommended during pregnancy and in women of childbearing potential not using contraception unless clearly necessary.

As with other antiepileptic medicinal products, physiological changes during pregnancy may affect Tiralepsyconcentration. Decrease in Tiralepsyplasma 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 Tiralepsyshould be ensured. Discontinuation of antiepileptic treatments may result in exacerbation of the disease which could be harmful to the mother and the foetus.

Breastfeeding

Tiralepsyis excreted in human breast milk. Therefore, breast-feeding is not recommended.

However, if Tiralepsytreatment is needed during breastfeeding, the benefit/risk of the treatment should be weighed considering the importance of breastfeeding.

Fertility

No impact on fertility was detected, potential risk for human is unknown.

Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

Due to possible different individual sensitivity, some patients might experience somnolence or other central nervous system related symptoms, especially at the beginning of treatment or following a dose increase. Therefore, caution is recommended in those patients when performing skilled tasks, e.g. driving vehicles or operating machinery. Patients are advised not to drive or use machines until it is established that their ability to perform such activities is not affected.

Overdose

Symptoms

Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Tiralepsy overdoses.

Management of overdose

After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. There is no specific antidote for Tiralepsy. Treatment of an overdose will be symptomatic and may include haemodialysis. The dialyser extraction efficiency is 60 % for Tiralepsyand 74 % for the primary metabolite.

Special precautions for storage

Store at temperature not exceeding 30 C, in a dry place.