1. Name of the medicinal product

Levetiracetam oral suspension USP 100mg/ml Taj Pharma

  1. Qualitative and quantitative composition

Each ml of oral suspension contains:
Levetiracetam USP 100mg
Excipients: Q.S.

Excipients with known effect: Each ml contains 1.5mg of methyl parahydroxybenzoate, 0.18mg of propyl parahydroxybenzoate and 300mg of maltitol liquid.

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Oral suspension solution.
A clear, colourless grape flavoured liquid.

  1. Clinical particulars
  • Therapeutic indications

Levetiracetam Taj Pharma oral solution 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.

Levetiracetam Taj Pharma oral solution is indicated as adjunctive therapy

  • in the treatment of partial onset seizures with or without secondary generalisation in adults, adolescents, children and infants from 1 month 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 generalised tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.

Posology and method of administration

Posology

Monotherapy for adults and adolescents from 16 years of age

The recommended starting dose is 250mg twice daily which should be increased to an initial therapeutic dose of 500mg twice daily after two weeks. The dose can be further increased by 250mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500mg 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 500mg 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 1,500mg twice daily. Dose changes can be made in 500mg twice daily increases or decreases every two to four weeks.

Special populations

Elderly (65 years and older)

Adjustment of the dose is recommended in elderly patients with compromised renal function (see “Renal impairment” below).

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) inml/min is needed. The CLcr inml/min may be estimated from serum creatinine (mg/dl) determination, for adults and adolescents weighting 50 kg or more, the following formula:

Then CLcr is adjusted for body surface area (BSA) as follows:

Dosing adjustment for adult and adolescents patients weighing more than 50 kg with impaired renal function:

GroupCreatinine clearance

(ml/min/1.73 m2)

Dose and frequency
Normal> 80500 to 1,500mg twice daily
Mild50-79500 to 1,000mg twice daily
Moderate30-49250 to 750mg twice daily
Severe< 30250 to 500mg twice daily
End-stage renal disease patients undergoing dialysis (1)500 to 1,000mg once daily (2)

(1) A 750mg loading dose is recommended on the first day of treatment with Levetiracetam Taj Pharma.

(2) Following dialysis, a 250 to 500mg supplemental dose is recommended.

For children with renal impairment, Levetiracetam Taj Pharma dose needs to be adjusted based on the renal function as Levetiracetam Taj Pharma clearance is related to renal function. This recommendation is based on a study in adult renally impaired patients.

The CLcr inml/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):

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:

GroupCreatinine clearance

(ml/min/1.73 m2)

Dose and frequency (1)
Infants 1 to less than 6 monthsInfants 6 to 23 months, children and adolescents weighing less than 50 kg
Normal> 807 to 21mg/kg (0.07 to 0.21ml/kg) twice daily10 to 30mg/kg (0.10 to 0.30ml/kg) twice daily
Mild50-797 to 14mg/kg (0.07 to 0.14ml/kg) twice daily10 to 20mg/kg (0.10 to 0.20ml/kg) twice daily
Moderate30-493.5 to 10.5mg/kg (0.035 to 0.105ml/kg) twice daily5 to 15mg/kg (0.05 to 0.15ml/kg) twice daily
Severe< 303.5 to 7mg/kg (0.035 to 0.07ml/kg) twice daily5 to 10mg/kg (0.05 to 0.10ml/kg) twice daily
End-stage renal disease patients undergoing dialysis7 to 14mg/kg (0.07 to 0.14ml/kg) once daily (2) (4)10 to 20mg/kg (0.10 to 0.20ml/kg) once daily (3) (5)

(1) Levetiracetam Taj Pharma oral solution should be used for doses under 250mg and for patients unable to swallow tablets.

(2) A 10.5mg/kg (0.105ml/kg) loading dose is recommended on the first day of treatment with Levetiracetam Taj Pharma.

(3) A 15mg/kg (0.15ml/kg) loading dose is recommended on the first day of treatment with Levetiracetam Taj Pharma.

(4) Following dialysis, a 3.5 to 7mg/kg (0.035 to 0.07ml/kg) supplemental dose is recommended.

(5) Following dialysis, a 5 to 10mg/kg (0.05 to 0.10ml/kg) supplemental dose is recommended.

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 < 60ml/min/1.73 m2.

Paediatric population

The physician should prescribe the most appropriate pharmaceutical form, presentation and strength according to age, weight and dose.

Levetiracetam Taj Pharma oral solution is the preferred formulation for use in infants and children under the age of 6 years. 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 250mg. In all of the above cases Levetiracetam Taj Pharma oral solution should be used.

Monotherapy

The safety and efficacy of Levetiracetam Taj Pharma oral solution in children and adolescents below 16 years as monotherapy have not yet been established.
There are no data available.
Add-on therapy for infants aged 6 to 23 months, children (2 to 11 years) and adolescents (12 to 17 years) weighing less than 50 kg

The initial therapeutic dose is 10mg/kg twice daily.

Depending upon the clinical response and tolerability, the dose can be increased up to 30mg/kg twice daily. Dose changes should not exceed increases or decreases of 10mg/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 infants from 6 months of age, children and adolescents:

WeightStarting dose:

10mg/kg twice daily

Maximum dose:

30mg/kg twice daily

6 kg (1)60mg (0.6ml) twice daily180mg (1.8ml) twice daily
10 kg (1)100mg (1ml) twice daily300mg (3ml) twice daily
15 kg (1)150mg (1.5ml) twice daily450mg (4.5ml) twice daily
20 kg (1)200mg (2ml) twice daily600mg (6ml) twice daily
25 kg (1)250mg twice daily750mg twice daily
From 50 kg (2)500mg twice daily1,500mg twice daily

(1) Children 25 kg or less should preferably start the treatment with Levetiracetam Taj Pharma.

(2) Dose in children and adolescents 50 kg or more is the same as in adults.

Add-on therapy for infants aged from 1 month to less than 6 months

The initial therapeutic dose is 7mg/kg twice daily.

Depending upon the clinical response and tolerability, the dose can be increased up to 21mg/kg twice daily. Dose changes should not exceed increases or decreases of 7mg/kg twice daily every two weeks. The lowest effective dose should be used.

Infants should start the treatment with Levetiracetam Taj Pharma.

Dose recommendations for infants aged from 1 month to less than 6 months:

WeightStarting dose:

7mg/kg twice daily

Maximum dose:

21mg/kg twice daily

4 kg28mg (0.3ml) twice daily84mg (0.85ml) twice daily
5 kg35mg (0.35ml) twice daily105mg (1.05ml) twice daily
7 kg49mg (0.5ml)twice daily147mg (1.5ml) twice daily

Three presentations are available:

– A 300ml bottle with a 10ml oral syringe (containing up to 1000mg Levetiracetam Taj Pharma) graduated every 0.25ml (corresponding to 25mg).

This presentation should be prescribed for children aged 4 years and older, adolescents and adults.

– A 150ml bottle with a 3ml oral syringe (containing up to 300mg Levetiracetam Taj Pharma) graduated every 0.1ml (corresponding to 10mg)

In order to ensure the accuracy of the dosing, this presentation should be prescribed for infants and young children aged from 6 months to less than 4 years.

– A 150ml bottle with a 1ml oral syringe (containing up to 100mg Levetiracetam Taj Pharma) graduated every 0.05ml (corresponding to 5mg)

In order to ensure the accuracy of the dosing, this presentation should be prescribed for infants aged 1 month to less than 6 months.

Method of administration

The oral solution may be diluted in a glass of water or baby’s bottle and may be taken with or without food. A graduated oral syringe, an adaptor for the syringe and instructions for use in the package leaflet are provided with Levetiracetam Taj Pharma.

The daily dose is administered in two equally divided doses.

  • Contraindications

Hypersensitivity to the active substance(s) or other pyrrolidone derivatives or to any of the excipients listed in section 6.1.

  • Special warnings and precautions for use

Discontinuation

In accordance with current clinical practice, if Levetiracetam Taj Pharma oral solution has to be discontinued it is recommended to withdraw it gradually (e.g. in adults and adolescents weighing more than 50 kg: 500mg 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 10mg/kg twice daily every two weeks; in infants (less than 6 months): dose decrease should not exceed 7mg/ kg twice daily every two weeks).

Renal insufficiency

The administration of Levetiracetam Taj Pharma oral solution 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 (see section 4.2).

Suicide

Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including Levetiracetam Taj Pharma). A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known.

Therefore, patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.

Paediatric population

Available data in children did not suggest impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.

The safety and efficacy of Levetiracetam Taj Pharma has not been thoroughly assessed in infants with epilepsy aged less than 1 year. Only 35 infants aged less than 1 year with partial onset seizures have been exposed in clinical studies of which only 13 were aged < 6 months.

Excipients

Levetiracetam Taj Pharma oral solution includes methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) which may cause allergic reactions (possibly delayed).

It also includes maltitol liquid (E965); patients with rare hereditary problems of fructose intolerance should not take this medicinal product.

  • Interaction with other medicinal products and other forms of interaction

Antiepileptic medicinal products

Pre-marketing data from clinical studies conducted in adults indicate that Levetiracetam Taj Pharma 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 Levetiracetam Taj Pharma.

As in adults, there is no evidence of clinically significant medicinal product interactions in paediatric patients receiving up to 60mg/kg/day Levetiracetam Taj Pharma.

A retrospective assessment of pharmacokinetic interactions in children and adolescents with epilepsy (4 to 17 years) confirmed that adjunctive therapy with orally administered Levetiracetam Taj Pharma did not influence the steady-state serum concentrations of concomitantly administered carbamazepine and valproate. However, data suggested a 20 % higher Levetiracetam Taj Pharma clearance in children taking enzyme-inducing antiepileptic medicinal products. Dose adjustment is not required.

Probenecid

Probenecid (500mg 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 Taj Pharma. 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 Levetiracetam Taj Pharma on probenecid was not studied and the effect of Levetiracetam Taj Pharma on other actively secreted medicinal products, e.g. NSAIDs, sulfonamides and methotrexate, is unknown.

Oral contraceptives and other pharmacokinetics interactions

Levetiracetam 1,000mg daily did not influence the pharmacokinetics of oral contraceptives (ethinyl-estradiol and levonorgestrel); endocrine parameters (luteinizing hormone and progesterone) were not modified. Levetiracetam 2,000mg 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 Levetiracetam Taj Pharma.

Antacids

No data on the influence of antacids on the absorption of Levetiracetam Taj Pharma are available.

Laxatives

There have been isolated reports of decreased Levetiracetam Taj Pharma efficacy when the osmotic laxative macrogol has been concomitantly administered with oral Levetiracetam Taj Pharma. Therefore, macrogol should not be taken orally for one hour before and for one hour after taking Levetiracetam Taj Pharma.

Food and alcohol

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

No data on the interaction of Levetiracetam Taj Pharma with alcohol are available.

  • Fertility, pregnancy and lactation

Pregnancy

Postmarketing data from several prospective pregnancy registries have documented outcomes in over 1000 women exposed to Levetiracetam Taj Pharma monotherapy during the first trimester of pregnancy. Overall, these data do not suggest a substantial increase in the risk for major congenital malformations, although a teratogenic risk cannot be completely excluded. Therapy with multiple antiepileptic medicinal products is associated with a higher risk of congenital malformations than monotherapy and therefore monotherapy should be considered. Studies in animals have shown reproductive toxicity (see section 5.3).

Levetiracetam Taj Pharma oral solution is not recommended during pregnancy and in women of childbearing potential not using contraception unless clinically necessary.

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

Breastfeeding

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

However, if Levetiracetam Taj Pharma treatment 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 in animal studies (see section 5.3). No clinical data are available, 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.

  • Undesirable effects

Summary of the safety profile

The adverse event profile presented below is based on the analysis of pooled placebo-controlled clinical trials with all indications studied, with a total of 3,416 patients treated with Levetiracetam Taj Pharma.

These data are supplemented with the use of Levetiracetam Taj Pharma in corresponding open-label extension studies, as well as post-marketing experience. The most frequently reported adverse reactions were nasopharyngitis, somnolence, headache, fatigue and dizziness. The safety profile of Levetiracetam Taj Pharma is generally similar across age groups (adult and paediatric patients) and across the approved epilepsy indications.

Tabulated list of adverse reactions

Adverse reactions reported in clinical studies (adults, adolescents, children and infants > 1 month) and from post-marketing experience are listed in the following table per System Organ Class and per frequency. The frequency is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000).

MedDRA SOCFrequency category
Very commonCommonUncommonRare
Infections and infestationsNasopharyngitisInfection
Blood and lymphatic system disordersThrombocytopenia, leukopeniaPancytopenia, Neutropenia, agranulocytosis
Immune system disordersDrug reaction with eosinophilia and systemic symptoms (DRESS)
Metabolism and Nutrition disordersAnorexiaWeight decreased , weight increaseHyponatraemia
Psychiatric disordersDepression, hostility/aggression, anxiety, insomnia, nervousness/irritabilitySuicide attempt, suicidal ideation, psychotic disorder, abnormal behaviour, hallucination, anger, confusional state , panic attack, affect lability/mood swings, agitationCompleted suicide, personality disorder, thinking abnormal
Nervous system disordersSomnolence, headacheConvulsion, balance disorder, dizziness, lethargy, tremorAmnesia, memory impairment, coordination abnormal/ataxia, paraesthesia, disturbance in attentionChoreoathetosis, dyskinesia, hyperkinesia
Eye disordersDiplopia, vision blurred
Ear and labyrinth disordersVertigo
Respiratory, thoracic and mediastinal disordersCough
Gastrointestinal disordersAbdominal pain, diarrhoea, dyspepsia, vomiting, nauseaPancreatitis
Hepatobiliary disordersLiver function test abnormalHepatic failure, hepatitis
Skin and subcutaneous tissue disordersRashAlopecia, eczema, pruritus,Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme
Musculoskeletal and connective tissue disordersMuscular weakness, myalgia
General disorders and administration site conditionsAsthenia/fatigue
Injury, poisoning and procedural complicationsInjury

Description of selected adverse reactions

The risk of anorexia is higher when topiramate is co-administered with Levetiracetam Taj Pharma.

In several cases of alopecia, recovery was observed when Levetiracetam Taj Pharma was discontinued.

Bone marrow suppression was identified in some of the cases of pancytopenia.

Paediatric population

In patients aged 1 month to less than 4 years, a total of 190 patients have been treated with Levetiracetam Taj Pharma in placebo-controlled and open label extension studies. Sixty (60) of these patients were treated with Levetiracetam Taj Pharma in placebo-controlled studies. In patients aged 4-16 years, a total of 645 patients have been treated with Levetiracetam Taj Pharma in placebo-controlled and open label extension studies. 233 of these patients were treated with Levetiracetam Taj Pharma in placebo-controlled studies. In both these paediatric age ranges, these data are supplemented with the post-marketing experience of the use of Levetiracetam Taj Pharma.

The adverse event profile of Levetiracetam Taj Pharma is generally similar across age groups and across the approved epilepsy indications. Safety results in paediatric patients in placebo-controlled clinical studies were consistent with the safety profile of Levetiracetam Taj Pharma in adults except for behavioural and psychiatric adverse reactions which were more common in children than in adults. In children and adolescents aged 4 to 16 years, vomiting (very common, 11.2%), agitation (common, 3.4%), mood swings (common, 2.1%), affect lability (common, 1.7%), aggression (common, 8.2%), abnormal behaviour (common, 5.6%), and lethargy (common, 3.9%) were reported more frequently than in other age ranges or in the overall safety profile. In infants and children aged 1 month to less than 4 years, irritability (very common, 11.7%) and coordination abnormal (common, 3.3%) were reported more frequently than in other age groups or in the overall safety profile.

A double-blind, placebo-controlled paediatric safety study with a non-inferiority design has assessed the cognitive and neuropsychological effects of Levetiracetam Taj Pharma in children 4 to 16 years of age with partial onset seizures. It was concluded that Levetiracetam Taj Pharma was not different (non inferior) from placebo with regard to the change from baseline of the Leiter-R Attention and Memory, Memory Screen Composite score in the per-protocol population. Results related to behavioural and emotional functioning indicated a worsening in Levetiracetam Taj Pharma treated patients on aggressive behaviour as measured in a standardised and systematic way using a validated instrument (CBCL – Achenbach Child Behavior Checklist). However subjects, who took Levetiracetam Taj Pharma in the long-term open label follow-up study, did not experience a worsening, on average, in their behavioural and emotional functioning; in particular measures of aggressive behaviour were not worse than baseline.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

  • Overdose

Symptoms

Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Levetiracetam Taj Pharma oral solution 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 Levetiracetam Taj Pharma. Treatment of an overdose will be symptomatic and may include haemodialysis. The dialyser extraction efficiency is 60 % for Levetiracetam Taj Pharma and 74 % for the primary metabolite.

  1. Pharmacological properties
  • Pharmacodynamic properties

Pharmacotherapeutic group: antiepileptics, other antiepileptics

The active substance, Levetiracetam Taj Pharma, is a pyrrolidone derivative (S-enantiomer of α-ethyl-2-oxo-1-pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substances.

Mechanism of action

The mechanism of action of Levetiracetam Taj Pharma still remains to be fully elucidated but appears to be different from the mechanisms of current antiepileptic medicinal products. In vitro and in vivo experiments suggest that Levetiracetam Taj Pharma does not alter basic cell characteristics and normal neurotransmission.

In vitro studies show that Levetiracetam Taj Pharma affects intraneuronal Ca2+ levels by partial inhibition of N-type Ca2+ currents and by reducing the release of Ca2+ from intraneuronal stores. In addition it partially reverses the reductions in GABA- and glycine-gated currents induced by zinc and β-carbolines. Furthermore, Levetiracetam Taj Pharma has been shown in in vitro studies to bind to a specific site in rodent brain tissue. This binding site is the synaptic vesicle protein 2A, believed to be involved in vesicle fusion and neurotransmitter exocytosis. Levetiracetam and related analogs show a rank order of affinity for binding to the synaptic vesicle protein 2A which correlates with the potency of their anti-seizure protection in the mouse audiogenic model of epilepsy. This finding suggests that the interaction between Levetiracetam Taj Pharma and the synaptic vesicle protein 2A seems to contribute to the antiepileptic mechanism of action of the medicinal product.

Pharmacodynamic effects

Levetiracetam induces seizure protection in a broad range of animal models of partial and primary generalised seizures without having a pro-convulsant effect. The primary metabolite is inactive. In man, an activity in both partial and generalised epilepsy conditions (epileptiform discharge/photoparoxysmal response) has confirmed the broad spectrum pharmacological profile of Levetiracetam Taj Pharma.

Clinical efficacy and safety

Adjunctive therapy in the treatment of partial onset seizures with or without secondary generalisation in adults, adolescents, children and infants from 1 month of age with epilepsy.

In adults, Levetiracetam Taj Pharma efficacy has been demonstrated in 3 double-blind, placebo-controlled studies at 1000mg, 2000mg, or 3000mg/day, given in 2 divided doses, with a treatment duration of up to 18 weeks. In a pooled analysis, the percentage of patients who achieved 50% or greater reduction from baseline in the partial onset seizure frequency per week at stable dose (12/14 weeks) was of 27.7 %, 31.6 % and 41.3 % for patients on 1000, 2000 or 3000mg Levetiracetam Taj Pharma respectively and of 12.6 % for patients on placebo.

Paediatric population

In paediatric patients (4 to 16 years of age), Levetiracetam Taj Pharma efficacy was established in a double-blind, placebo-controlled study, which included 198 patients and had a treatment duration of 14 weeks. In this study, the patients received Levetiracetam Taj Pharma as a fixed dose of 60mg/kg/day (with twice a day dosing).

44.6 % of the Levetiracetam Taj Pharma treated patients and 19.6 % of the patients on placebo had a 50 % or greater reduction from baseline in the partial onset seizure frequency per week. With continued long term treatment, 11.4 % of the patients were seizure-free for at least 6 months and 7.2 % were seizure free for at least 1 year.

In paediatric patients (1 month to less than 4 years of age), Levetiracetam Taj Pharma efficacy was established in a double-blind, placebo-controlled study, which included 116 patients and had a treatment duration of 5 days. In this study, patients were prescribed 20mg/kg, 25mg/kg, 40mg/kg or 50mg/kg daily dose of oral solution based on their age titration schedule. A dose of 20mg/kg/day titrating to 40mg/kg/day for infants one month to less than six months and a dose of 25mg/kg/day titrating to 50mg/kg/day for infants and children 6 months to less than 4 years old, was use in this study. The total daily dose was administered b.i.d. The primary measure of effectiveness was the responder rate (percent of patient 50% reduction from baseline in average daily partial onset seizure frequency) assessed by a blinded central reader using a 48-hour video EEG. The efficacy analysis consisted of 109 patients who had at least 24 hours of video EEG in both baseline and evaluation periods. 43.6 % of the Levetiracetam Taj Pharma treated patients and 19.6 % of the patients on placebo were considered as responders. The results are consistent across age group. With continued long- term treatment, 8.6 % of the patients were seizure free for at least 6 months and 7.8 % were seizure-free for at least 1 year.

Monotherapy in the treatment of partial onset seizures with or without secondary generalisation in patients from 16 years of age with newly diagnosed epilepsy.

Efficacy of Levetiracetam Taj Pharma as monotherapy was established in a double-blind, parallel group, non-inferiority comparison to carbamazepine controlled release (CR) in 576 patients 16 years of age or older with newly or recently diagnosed epilepsy. The patients had to present with unprovoked partial seizures or with generalized tonic-clonic seizures only. The patients were randomized to carbamazepine CR 400 – 1200mg/day or Levetiracetam Taj Pharma 1000 – 3000mg/day, the duration of the treatment was up to 121 weeks depending on the response.

Six-month seizure freedom was achieved in 73.0 % of Levetiracetam Taj Pharma-treated patients and 72.8 % of carbamazepine-CR treated patients; the adjusted absolute difference between treatments was 0.2% (95 % CI: -7.8 8.2). More than half of the subjects remained seizure free for 12 months (56.6 % and 58.5 % of subjects on Levetiracetam Taj Pharma and on carbamazepine CR respectively).

In a study reflecting clinical practice, the concomitant antiepileptic medication could be withdrawn in a limited number of patients who responded to Levetiracetam Taj Pharma adjunctive therapy (36 adult patients out of 69).

Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy.

Levetiracetam efficacy was established in a double-blind, placebo-controlled study of 16 weeks duration, in patients 12 years of age and older suffering from idiopathic generalized epilepsy with myoclonic seizures in different syndromes. The majority of patients presented with juvenile myoclonic epilepsy.

In this study, Levetiracetam Taj Pharma, dose was 3000mg/day given in 2 divided doses.

58.3 % of the Levetiracetam Taj Pharma treated patients and 23.3 % of the patients on placebo had at least a 50 % reduction in myoclonic seizure days per week. With continued long-term treatment, 28.6 % of the patients were free of myoclonic seizures for at least 6 months and 21.0 % were free of myoclonic seizures for at least 1 year.

Adjunctive therapy in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with idiopathic generalised epilepsy.

Levetiracetam efficacy was established in a 24-week double-blind, placebo-controlled study which included adults, adolescents and a limited number of children suffering from idiopathic generalized epilepsy with primary generalized tonic-clonic (PGTC) seizures in different syndromes (juvenile myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy, or epilepsy with Grand Mal seizures on awakening). In this study, Levetiracetam Taj Pharma dose was 3000mg/day for adults and adolescents or 60mg/kg/day for children, given in 2 divided doses.

72.2 % of the Levetiracetam Taj Pharma treated patients and 45.2 % of the patients on placebo had a 50 % or greater decrease in the frequency of PGTC seizures per week. With continued long-term treatment, 47.4 % of the patients were free of tonic-clonic seizures for at least 6 months and 31.5 % were free of tonic-clonic seizures for at least 1 year.

  • Pharmacokinetic properties

Levetiracetam is a highly soluble and permeable compound. The pharmacokinetic profile is linear with low intra- and inter-subject variability. There is no modification of the clearance after repeated administration. There is no evidence for any relevant gender, race or circadian variability. The pharmacokinetic profile is comparable in healthy volunteers and in patients with epilepsy.

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

A significant correlation between saliva and plasma concentrations has been shown in adults and children (ratio of saliva/plasma concentrations ranged from 1 to 1.7 for oral tablet formulation and after 4 hours post-dose for oral solution formulation).

Adults and adolescents

Absorption

Levetiracetam is rapidly absorbed after oral administration. Oral absolute bioavailability is close to 100 %.

Peak plasma concentrations (Cmax) are achieved at 1.3 hours after dosing. Steady-state is achieved after two days of a twice daily administration schedule.

Peak concentrations (Cmax) are typically 31 and 43 μg/ml following a single 1,000mg dose and repeated 1,000mg twice daily dose, respectively.

The extent of absorption is dose-independent and is not altered by food.

Distribution

No tissue distribution data are available in humans.

Neither Levetiracetam Taj Pharma nor its primary metabolite are significantly bound to plasma proteins (<10 %).

The volume of distribution of Levetiracetam Taj Pharma is approximately 0.5 to 0.7 l/kg, a value close to the total body water volume.

Biotransformation

Levetiracetam is not extensively metabolised in humans. The major metabolic pathway (24 % of the dose) is an enzymatic hydrolysis of the acetamide group. Production of the primary metabolite, ucb L057, is not supported by liver cytochrome P450 isoforms. Hydrolysis of the acetamide group was measurable in a large number of tissues including blood cells. The metabolite ucb L057 is pharmacologically inactive.

Two minor metabolites were also identified. One was obtained by hydroxylation of the pyrrolidone ring (1.6 % of the dose) and the other one by opening of the pyrrolidone ring (0.9 % of the dose).

Other unidentified components accounted only for 0.6 % of the dose.

No enantiomeric interconversion was evidenced in vivo for either Levetiracetam Taj Pharma or its primary metabolite.

In vitro, Levetiracetam Taj Pharma and its primary metabolite have been shown not to inhibit the major human liver cytochrome P450 isoforms (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 and 1A2), glucuronyl transferase (UGT1A1 and UGT1A6) and epoxide hydroxylase activities. In addition, Levetiracetam Taj Pharma does not affect the in vitro glucuronidation of valproic acid.

In human hepatocytes in culture, Levetiracetam Taj Pharma had little or no effect on CYP1A2, SULT1E1 or UGT1A1. Levetiracetam caused mild induction of CYP2B6 and CYP3A4. The in vitro data and in vivo interaction data on oral contraceptives, digoxin and warfarin indicate that no significant enzyme induction is expected in vivo. Therefore, the interaction of Levetiracetam Taj Pharma oral solution with other substances, or vice versa, is unlikely.

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 0.96ml/min/kg.

The major route of excretion was via urine, accounting for a mean 95 % of the dose (approximately 93 % of the dose was excreted within 48 hours). Excretion via faeces accounted for only 0.3 % of the dose.

The cumulative urinary excretion of Levetiracetam Taj Pharma and its primary metabolite accounted for 66 % and 24 % of the dose, respectively during the first 48 hours.

The renal clearance of Levetiracetam Taj Pharma and ucb L057 is 0.6 and 4.2ml/min/kg respectively indicating that Levetiracetam Taj Pharma is excreted by glomerular filtration with subsequent tubular reabsorption and that the primary metabolite is also excreted by active tubular secretion in addition to glomerular filtration.

Levetiracetam elimination is correlated to creatinine clearance.

Elderly

In the elderly, the half-life is increased by about 40 % (10 to 11 hours). This is related to the decrease in renal function in this population (see section 4.2).

Renal impairment

The apparent body clearance of both Levetiracetam Taj Pharma and of its primary metabolite is correlated to the creatinine clearance. It is therefore recommended to adjust the maintenance daily dose of Levetiracetam Taj Pharma, based on creatinine clearance in patients with moderate and severe renal impairment (see section 4.2).

In anuric end-stage renal disease adult subjects the half-life was approximately 25 and 3.1 hours during interdialytic and intradialytic periods, respectively.

The fractional removal of Levetiracetam Taj Pharma was 51 % during a typical 4-hour dialysis session.

Hepatic impairment

In subjects with mild and moderate hepatic impairment, there was no relevant modification of the clearance of Levetiracetam Taj Pharma. In most subjects with severe hepatic impairment, the clearance of Levetiracetam Taj Pharma was reduced by more than 50 % due to a concomitant renal impairment (see section 4.2).

Paediatric population

Children (4 to 12 years)

Following single oral dose administration (20mg/kg) to epileptic children (6 to 12 years), the half-life of Levetiracetam Taj Pharma was 6.0 hours. The apparent body weight adjusted clearance was approximately 30 % higher than in epileptic adults.

Following repeated oral dose administration (20 to 60mg/kg/day) to epileptic children (4 to 12 years), Levetiracetam Taj Pharma was rapidly absorbed. Peak plasma concentration was observed 0.5 to 1.0 hour after dosing. Linear and dose proportional increases were observed for peak plasma concentrations and area under the curve. The elimination half-life was approximately 5 hours. The apparent body clearance was 1.1ml/min/kg.

Infants and children (1 month to 4 years)

Following single dose administration (20mg/kg) of a 100mg/ml oral solution to epileptic children (1 month to 4 years), Levetiracetam Taj Pharma was rapidly absorbed and peak plasma concentrations were observed approximately 1 hour after dosing. The pharmacokinetic results indicated that half-life was shorter (5.3 h) than for adults (7.2 h) and apparent clearance was faster (1.5ml/min/kg) than for adults (0.96ml/min/kg).

In the population pharmacokinetic analysis conducted in patients from 1 month to 16 years of age, body weight was significantly correlated to apparent clearance (clearance increased with an increase in body weight) and apparent volume of distribution. Age also had an influence on both parameters. This effect was pronounced for the younger infants, and subsided as age increased, to become negligible around 4 years of age.

In both population pharmacokinetic analyses, there was about a 20 % increase of apparent clearance of Levetiracetam Taj Pharma when it was co-administered with an enzyme-inducing antiepileptic medicinal product.

  • Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity and carcinogenicity.

Adverse effects not observed in clinical studies but seen in the rat and to a lesser extent in the mouse at exposure levels similar to human exposure levels and with possible relevance for clinical use were liver changes, indicating an adaptive response such as increased weight and centrilobular hypertrophy, fatty infiltration and increased liver enzymes in plasma.

No adverse effects on male or female fertility or reproduction performance were observed in rats at doses up to 1800mg/kg/day (x 6 the MRHD on amg/m2 or exposure basis) in parents and F1 generation.

Two embryo-fetal development (EFD) studies were performed in rats at 400, 1200 and 3600mg/kg/day. At 3600mg/kg/day, in only one of the 2 EFD studies, there was a slight decrease in fetal weight associated with a marginal increase in skeletal variations/minor anomalies. There was no effect on embryomortality and no increased incidence of malformations. The NOAEL (No Observed Adverse Effect Level) was 3600mg/kg/day for pregnant female rats (x 12 the MRHD on amg/m2 basis) and 1200mg/kg/day for fetuses.

Four embryo-fetal development studies were performed in rabbits covering doses of 200, 600, 800, 1200 and 1800mg/kg/day. The dose level of 1800mg/kg/day induced a marked maternal toxicity and a decrease in fetal weight associated with increased incidence of fetuses with cardiovascular/skeletal anomalies. The NOAEL was <200mg/kg/day for the dams and 200mg/kg/day for the fetuses (equal to the MRHD on amg/m2 basis).

A peri- and post-natal development study was performed in rats with Levetiracetam Taj Pharma doses of 70, 350 and 1800mg/kg/day. The NOAEL was ≥ 1800mg/kg/day for the F0 females, and for the survival, growth and development of the F1 offspring up to weaning (x 6 the MRHD on amg/m2 basis).

Neonatal and juvenile animal studies in rats and dogs demonstrated that there were no adverse effects seen in any of the standard developmental or maturation endpoints at doses up to 1800mg/kg/day (x 6- 17 the MRHD on amg/m2 basis)

Environmental Risk Assessment (ERA)

The use of Levetiracetam Taj Pharma oral solution in accordance with the product information is not likely to result in an unacceptable environmental impact (see section 6.6).

  1. Pharmaceutical particulars
    • List of excipients

Sodium citrate

Citric acid monohydrate

Methyl parahydroxybenzoate

Propyl parahydroxybenzoate

Ammonium glycyrrhizate

Glycerol

Maltitol liquid

Acesulfame potassium

Grape flavour containing propylene glycol

Purified water

  • Incompatibilities

Not applicable.

  • Shelf life

3 years

After first opening: 4 months

  • Special precautions for storage

This medicinal product does not require any special temperature storage conditions. Store in the original container in order to protect from light.

  • Nature and contents of container

300ml in amber glass bottle (type III) with child resistant closure (polypropylene) in a cardboard box also containing a 10ml graduated oral syringe (polyethylene, polystyrene) and an adaptor for the syringe (polyethylene).

150ml in amber glass bottle (type III) with child resistant closure (polypropylene) in a cardboard box also containing a 3ml graduated oral syringe (polyethylene, polystyrene) and an adaptor for the syringe (polyethylene).

150ml in amber glass bottle (type III) with child resistant closure (polypropylene) in a cardboard box also containing a 1ml graduated oral syringe (polyethylene, polystyrene) and an adaptor for the syringe (polyethylene).

  • Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Levetiracetam oral suspension USP 100mg/ml Taj Pharma

Package Leaflet: Information for the patient

Read all of this leaflet carefully before you or your child start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects talk to your doctor or pharmacist.

This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

  1. What Levetiracetam Taj Pharma Actavis Group is and what it is used for
  2. What you need to know before you take Levetiracetam Taj Pharma Actavis Group
  3. How to take Levetiracetam Taj Pharma Actavis Group
  4. Possible side effects
  5. How to store Levetiracetam Taj Pharma Actavis Group
  6. Contents of the pack and other information

1.What Levetiracetam Taj Pharma Actavis Group is and what it is used for

Levetiracetam Taj Pharma is an antiepileptic medicine (a medicine used to treat seizures in epilepsy).

Levetiracetam Taj Pharma Actavis Group is used:

  • on its own in adults and adolescents from 16 years of age with newly diagnosed epilepsy, to treat a certain form of epilepsy. Epilepsy is a condition where the patients have repeated fits (seizures). Levetiracetam Taj Pharma is used for the epilepsy form in which the fits initially affect only one side of the brain, but could thereafter extend to larger areas on both sides of the brain (partial onset seizure with or without secondary generalisation). Levetiracetam Taj Pharma has been given to you by your doctor to reduce the number of fits.
  • as an add-on to other antiepileptic medicines to treat:
  • partial onset seizures with or without generalization in adults, adolescents, children and infants from one month of age
  • myoclonic seizures (short, shock-like jerks of a muscle or group of muscles) in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy
  • primary generalised tonic-clonic seizures (major fits, including loss of consciousness) in adults and adolescents from 12 years of age with idiopathic generalised epilepsy (the type of epilepsy that is thought to have a genetic cause).
  1. What you need to know before you take Levetiracetam Taj Pharma

Actavis Group

Do not take Levetiracetam Taj Pharma Actavis Group

  • If you are allergic to Levetiracetam Taj Pharma, pyrrolidone derivatives or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor before taking Levetiracetam Taj Pharma Actavis Group

  • If you suffer from kidney problems, follow your doctor’s instructions. He/she may decide if your dose should be adjusted.
  • If you notice any slow down in the growth or unexpectedpuberty development of your child, please contact your doctor.
  • A small number of people being treated with antiepileptics such as Levetiracetam Taj Pharma have had thoughts of harming or killing themselves. If you have any symptoms of depression and/or suicidal ideation, please contact your doctor.

Children and adolescents

Levetiracetam Taj Pharma Actavis Group is not indicated in children and adolescents below 16 years on its own (monotherapy).

Other medicines and Levetiracetam Taj Pharma Actavis Group

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take macrogol (a drug used as laxative) for one hour before and one hour after taking Levetiracetam Taj Pharma as this may result in a reduction of its effect.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Levetiracetam Taj Pharma can be used during pregnancy, only if after careful assessment it is considered necessary by your doctor.

You should not stop your treatment without discussing this with your doctor. A risk of birth defects for your unborn child cannot be completely excluded. Breast-feeding is not recommended during treatment.

Driving and using machines

Levetiracetam Taj Pharma Actavis Group may impair your ability to drive or operate any tools or machinery, as it may make you feel sleepy. This is more likely at the beginning of treatment or after an increase in the dose. You should not drive or use machines until it is established that your ability to perform such activities is not affected.

Levetiracetam Taj Pharma Actavis Group contains methyl parahydroxybenzoate, propyl parahydroxybenzoate, maltitol, propylene glycol and sodium. Levetiracetam Taj Pharma Actavis Group oral solution includes methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate which may cause allergic reactions (possibly delayed).

Levetiracetam Taj Pharma Actavis Group oral solution also contains maltitol. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product. Levetiracetam Taj Pharma Actavis Group oral solution contains propylene glycol.

If your baby is less than 4 weeks old, talk to your doctor or pharmacist before giving them this medicine, in particular if the baby is given other medicines that contain propylene glycol or alcohol.

This medicine contains less than 1 mmol sodium (23 mg) perml, that is to say essentially ‘sodium-free’.

  1. How to take Levetiracetam Taj Pharma Actavis Group

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Levetiracetam Taj Pharma Actavis Group must be taken twice a day, once in the morning and once in the evening, at about the same time each day.

Take the oral solution following your doctor’s instructions.

Monotherapy

Dose in adults and adolescents from 16 years of age:

Measure the appropriate dosage using the 10ml syringe included in the package for patients 4 years and above.

General dose: Levetiracetam Taj Pharma Actavis Group is taken twice daily, in two equally divided doses, each individual dose being measured between 5ml (500 mg) and 15ml (1,500 mg).

When you will first start taking Levetiracetam Taj Pharma Actavis Group, your doctor will prescribe you a lower dose during 2 weeks before giving you the lowest general dose.

Add-on therapy

Dose in adults and adolescents (12 to 17 years):

Measure the appropriate dosage using the 10ml syringe included in the package for patients of 4 years and above.

General dose: Levetiracetam Taj Pharma Actavis Group is taken twice daily, in two equally divided doses, each individual dose being measured between 5ml (500 mg) and 15ml (1,500 mg).

Dose in children 6 months and older:

Your doctor will prescribe the most appropriate pharmaceutical form of Levetiracetam Taj Pharma according to the age, weight and dose.

For children 6 months to 4 years, measure the appropriate dosage using the 3ml syringe included in the package.

For children above 4 years, measure the appropriate dosage using the 10ml syringe included in the package.

General dose: Levetiracetam Taj Pharma Actavis Group is taken twice daily, in two equally divided doses, each individual dose being measured between 0.1ml (10 mg) and 0.3ml (30 mg), per kg bodyweight of the child. (see table below for dose examples).

Dose in children 6 months and older:

WeightStarting dose: 0.1ml/kg twice dailyMaximum dose: 0.3ml/kg twice daily
6 kg0.6ml twice daily1.8ml twice daily
8Kg0.8ml twice daily2.4ml twice daily
10Kg1ml twice daily3ml twice daily
15Kg1.5ml twice daily4.5ml twice daily
20Kg2ml twice daily6ml twice daily
25Kg2.5ml twice daily7.5ml twice daily
From 50Kg5ml twice daily15ml twice daily

 

Dose in infants (1 month to less than 6 months):

For infants 1 month to less than 6 months, measure the appropriate dosage using the 1ml syringe included in the package.

General dose: Levetiracetam Taj Pharma Actavis Group is taken twice daily, in two equally divided doses, each individual dose being measured between 0.07ml (7 mg) and 0.21ml (21 mg), per kg bodyweight of the infant. (see table below for dose examples).

Dose in infants (1 month to less than 6 months):

WeightStarting dose: 0.07ml/kg twice dailyMaximum dose: 0.21ml/kg twice daily
4kg0.3ml twice daily0.85ml twice daily
5kg0.35ml twice daily1.05ml twice daily
6kg0.45ml twice daily1.25ml twice daily
7kg0.5ml twice daily1.5ml twice daily

 

Method of administration:

After measuring the correct dose with an appropriate syringe,

Levetiracetam Taj Pharma Actavis Group oral solution may be diluted in a glass of water or baby’s bottle. You may take Levetiracetam Taj Pharma Actavis Group with or without food. After oral administration the bitter taste of Levetiracetam Taj Pharma may be experienced.

Instruction for use:

(1) Open the bottle. Before starting the measuring procedure make sure that the transparent dosing body of the syringe as well as the white plunger are in the bottom most position. To measure the dosing quantity, use one hand to hold the dosing body and the other hand to pull up the plunger until you reach the graduation mark corresponding to the quantity in milliliters (ml) prescribed by your doctor

Pull the syringe by the dosing body out of the bottle

Empty the contents of the syringe in a glass of water by pushing down the plunger. Be sure to drink the whole contents of the glass. The contents of the syringe can also be given directly from the syringe into the mouth or emptied onto a spoon

Wash the syringe with water after use and close the bottle with the plastic screw cap

Duration of treatment:

  • Levetiracetam Taj Pharma Actavis Group is used as a chronic treatment.

You should continue Levetiracetam Taj Pharma Actavis Group treatment for as long as your doctor has told you.

  • Do not stop your treatment without your doctor’s advice as this could increase your seizures.

If you take more Levetiracetam Taj Pharma Actavis Group than you should

The possible side effects of an overdose of Levetiracetam Taj Pharma Actavis Group are sleepiness, agitation, aggression, decrease of alertness, inhibition of breathing and coma.

Contact your doctor if you took more Levetiracetam Taj Pharma Actavis Group than you should. Your doctor will establish the best possible treatment of overdose.

If you forget to take Levetiracetam Taj Pharma Actavis Group

Contact your doctor if you have missed one or more doses.

Do not take a double dose to make up for a forgotten dose.

If you stop taking Levetiracetam Taj Pharma Actavis Group

If stopping treatment, Levetiracetam Taj Pharma Actavis Group should be discontinued gradually to avoid an increase of seizures.

Should your doctor decide to stop your Levetiracetam Taj Pharma Actavis Group treatment, he/she will instruct you about the gradual withdrawal of Levetiracetam Taj Pharma Actavis Group.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately, or go to your nearest emergency department, if you experience:

  • weakness, feel light-headed or dizzy or have difficulty breathing, as these may be signs of a serious allergic (anaphylactic) reaction;
  • swelling of the face, lips, tongue and throat (Quincke’s oedema);
  • flu-like symptoms and a rash on the face followed by an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]);
  • symptoms such as low urine volume, tiredness, nausea, vomiting, confusion and swelling in the legs, ankles or feet, as this may be a sign of sudden decrease of kidney function;
  • a skin rash which may form blisters and look like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme);
  • a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome);
  • a more severe form of rash causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis);
  • signs of serious mental changes or if someone around you notices signs of confusion, somnolence (sleepiness), amnesia (loss of memory), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary or uncontrolled movements.

These could be symptoms of an encephalopathy.

The most frequently reported adverse reactions were nasopharyngitis, somnolence (sleepiness), headache, fatigue and dizziness. At the beginning of the treatment or at dose increase side effects like sleepiness, tiredness and dizziness may be more common. These effects should however decrease over time.

Very common: may affect more than 1 in 10 people

  • nasopharyngitis;
  • somnolence (sleepiness), headache.

Common: may affect up to 1 in 10 people

  • anorexia (loss of appetite);
  • depression, hostility or aggression, anxiety, insomnia, nervousness or irritability;
  • convulsion, balance disorder (equilibrium disorder), dizziness (sensation of unsteadiness), lethargy (lack of energy and enthusiasm), tremor (involuntary trembling);
  • vertigo (sensation of rotation);
  • cough;
  • abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea;
  • rash;
  • asthenia/fatigue (tiredness).

Uncommon: may affect up to 1 in 100 people

  • decreased number of blood platelets, decreased number of white blood cells;
  • weight decrease, weight increase;
  • suicide attempt and suicidal ideation, mental disorder, abnormal behaviour, hallucination, anger, confusion, panic attack, emotional instability/mood swings, agitation;
  • amnesia (loss of memory), memory impairment (forgetfulness), abnormal coordination/ataxia (impaired coordinated movements), paraesthesia (tingling), disturbance in attention (loss of concentration);
  • diplopia (double vision), vision blurred;
  • elevated/abnormal values in a liver function test;
  • hair loss, eczema, pruritus;
  • muscle weakness, myalgia (muscle pain);

Rare: may affect up to 1 in 1,000 people

  • infection;
  • decreased number of all blood cell types;
  • severe allergic reactions (DRESS, anaphylactic reaction [severe and important allergic reaction], Quincke’s oedema [swelling of the face, lips, tongue and throat]);
  • decreased blood sodium concentration;
  • suicide, personality disorders (behavioural problems), thinking abnormal (slow thinking, unable to concentrate);
  • delirium;
  • encephalopathy (see sub-section “Tell your doctor immediately” for a detailed description of symptoms);
  • uncontrollable muscle spasms affecting the head, torso and limbs, difficulty in controlling movements, hyperkinesia (hyperactivity);
  • pancreatitis;
  • liver failure, hepatitis;
  • sudden decrease in kidney function;
  • skin rash, which may form blisters and looks like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme), a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (StevensJohnson syndrome), and a more severe form causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis).
  • rhabdomyolysis (breakdown of muscle tissue) and associated blood creatine phosphokinase increase.

Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.

  • limp or difficulty walking.

Reporting of side effects

If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Levetiracetam Taj Pharma Actavis Group

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the cardboard box and bottle after EXP:

The expiry date refers to the last day of that month.

Do not use after 7 months of first opening the bottle.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information

What Levetiracetam Taj Pharma Actavis Group contains

The active substance is called Levetiracetam Taj Pharma. Eachml contains 100 mg of Levetiracetam Taj Pharma.

The other ingredients are: sodium citrate, citric acid monohydrate, methyl parahydroxybenzoate, propyl parahydroxybenzoate, ammonium glycyrrhizate, glycerin, glycerol, maltitol liquid, acesulfame potassium, grape flavour (contains propylene glycol), purified water.

What Levetiracetam Taj Pharma Actavis Group looks like and contents of the pack

Levetiracetam Taj Pharma Actavis Group 100 mg/ml oral solution is a clear, faint yellowish-brown solution.

The 300ml glass bottle of Levetiracetam Taj Pharma Actavis Group (for children aged 4 years and above, adolescents and adults) is packed in a cardboard box containing a 10ml oral syringe (graduated every 0.25ml).

The 300ml glass bottle of Levetiracetam Taj Pharma Actavis Group (for infants and young children aged from 6 months to less than 4 years) is packed in a cardboard box containing a 3ml oral syringe (graduated every 0.1ml) and an adaptor for the syringe.

The 300ml glass bottle of Levetiracetam Taj Pharma Actavis Group (for infants aged 1 month to less than 6 months) is packed in a cardboard box containing a 1ml oral syringe (graduated every 0.05ml) and an adaptor for the syringe.

Not all pack sizes may be marketed.

Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com