Keppra Oral 100 mg Oral Solution

KEPPRA is indicated as adjunctive therapy in the treatment of partial onset seizures with or without secondary generalization in adults and children from 4 years of age with epilepsy.

The oral solution may be diluted in a glass of water and may be taken with or without food. A graduated oral syringe and instructions for use in the patient information leaflet are provided with the oral solution. The daily dose is administered in two equal divided doses.

Adults (> 18 years) and adolescents (12 to 17 years): As adjunctive therapy, 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 tolerance, the daily dose can be increased up to 1 500 mg twice daily. Dose changes can be made in 500 mg twice daily increments or decrements every two to four weeks. The maximum daily dose is 3 000 mg.

Elderly (65 years and older): Adjustment of the dose is recommended in elderly patients with compromised renal function (see u2018 Patients with renal impairment u2019 below).

Children aged 4 to 11 years: The initial dose is 10 mg/kg twice daily. This dose can be started on the first day of treatment. Depending upon the clinical response and tolerance, the daily dose can be increased up to 30 mg/kg twice daily. Dose changes can be made in 10 mg/kg twice daily increments or decrements every two weeks. Dosage in children 50 kg or greater is the same as in adults.

Infants and children less than 4 years: There is insufficient data to recommend the use of KEPPRA in children under 4 years of age.

Patients with renal impairment: The KEPPRA 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 patientu2019s creatinine clearance (C lcr) in ml/min is needed.

Hypersensitivity to levetiracetam or other pyrrolidone derivatives or any of the excipients. Patients with rare hereditary problems of fructose intolerance should not take KEPPRA oral solution. The use of KEPPRA is contra-indicated in pregnancy and lactation (see PREGNANCY AND LACTATION).

Due to its complete and linear absorption, plasma levels can be predicted from the oral dose of levetiracetam expressed as mg/kg bodyweight. Therefore, there is no need for plasma level monitoring of levetiracetam.

Discontinuation: If KEPPRA has to be discontinued, it is recommended to withdraw it gradually (e.g. 500 mg twice daily decrements every two to four weeks in adults: 10 mg/kg twice daily decrements every two weeks in children).

Seizure frequency: An increase in seizure frequency of more than 25 % was reported in 14 % of KEPPRA treated adult and paediatric patients, whereas it was reported in 26 % and 21 % of placebo treated adult and paediatric patients, respectively.

Renal insufficiency: The administration of KEPPRA to patients with renal impairment may require dose adaptation. In patients with severely impaired hepatic function, assessment of renal function is recommended before dose selection (see DOSAGE AND DIRECTIONS FOR USE).

Suicide: Suicide, suicide attempt and suicidal ideation have been reported in patients treated with KEPPRA. Patients should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician.

Data indicate that KEPPRA did not influence the serum concentration of existing antiepileptic medicines (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these antiepileptic medicines did not influence the pharmacokinetics of KEPPRA. As in adults, there is no clear evidence of clinically significant medicinal product interactions in paediatric patients receiving up to 60 mg/kg/day KEPPRA.

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. It is expected that medicines excreted by active tubular secretion could reduce the renal clearance of the metabolite. The effect of KEPPRA on probenecid and other actively secreted medicine like NSAIDs, sulphonamides and methotrexate, is unknown.

There is no adequate information on the use of KEPPRA during pregnancy. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown (see CONTRA - INDICATIONS). Physiological changes during pregnancy may affect levetiracetam concentration. There have been reports of decreased levetiracetam concentration during pregnancy. Safety in breastfeeding has not been established. Levetiracetam is excreted in human breast milk. Patients using KEPPRA should not breastfeed their babies (see CONTRA - INDICATIONS).

No studies on the effect on the ability to drive and use machines have been performed. Patients might experience somnolence or other CNS related symptoms. Therefore, caution is recommended in those patients when performing skilled tasks, e.g. driving vehicles or operating machinery.

The most commonly reported side effects are somnolence, asthenia and dizziness. The most commonly reported undesirable effects were somnolence, hostility, nervousness, emotional lability, agitation, anorexia, asthenia and headache in the paediatric population. Safety results in paediatric patients were consistent with the safety profile of KEPPRA in adults.

Undesirable effects reported in clinical studies (adults and children), the frequency is defined as follows:

• Very common (u2265 1/10)
• Common (u2265 1/100 to < 1/10)
• Uncommon (u2265 1/1 000 to < 1/100)
• Rare (u2265 1/10 000 to < 1/1 000)
• Very rare (< 1/10 000), including isolated reports, not known (cannot be estimated on available data).

System Organ Class Frequency Side effect Infections and infestations Common infection, nasopharyngitis Blood and lymphatic system disorders Common thrombocytopenia Metabolism and nutrition disorders Common anorexia, weight increase The risk of anorexia is higher when topiramate is co-administered with KEPPRA Psychiatric disorders Common aggression, agitation, depression, emotional lability/mood swings, hostility, insomnia, irritability, nervousness, personality disorders, abnormal thinking Nervous system disorders Very common Common somnolence/fatigue amnesia, ataxia, convulsion, dizziness, headache, hyperkinesia, tremour, balance disorder, disturbance in attention, memory impairment Eye disorders Common diplopia, blurred vision Ear and labyrinth disorders Common vertigo Respiratory, thoracic and mediastinal disorders Common cough increased Gastrointestinal disorders Common abdominal pain, diarrhoea, dyspepsia, nausea, vomiting Skin and subcutaneous tissue disorders Common eczema, pruritus, rash Musculoskeletal, connective tissue and bone disorders Common myalgia General disorders and administrative site conditions Very common asthenia Injury and poisoning Common accidental injury

There is no experience with doses greater than 5 000 mg/day orally. No serious adverse events were reported by healthy volunteers at single doses up to and including 5 000 mg orally. Symptoms of overdosage: somnolence, agitation, depressed level of consciousness, respiratory depression and coma. In acute, significant overdosage, the stomach may be emptied by gastric lavage or by induction of emesis. There is no specific antidote for levetiracetam. Treatment for an overdose will be symptomatic and may include haemodialysis. The dialyser extraction efficiency is 60 % for levetiracetam and 74 % for the metabolite ucb L057.